Theilheimer's Synthetic Methods of Organic Chemistry 81

Theilheimer's Synthetic Methods of Organic Chemistry

Bearbeitet vonG. Tozer-Hotchkiss

1. Auflage 2013. Buch. XXIV, 562 S. HardcoverISBN 978 3 318 02377 0

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Theilheimer’s

Synthetic Methods

of Organic Chemistry

81 2013

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SyntheticMethods

Theilheimer’s

of Organic Chemistry

Vol. 81

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Vol. 81 2013

SyntheticMethods

Theilheimer’s

of Organic Chemistry

Editor Gillian Tozer-Hotchkiss, Wirral, UK

Assistant Editors Alan F. Finch, Cambridge, UK Chris Hardy, Leeds, UK Julian Hayward, Leeds, UK

Technical Editor Jill Entwistle, Berkhamsted, UK

Basel • FreiburgParis • London • New York

New Delhi • BangkokBejing • TokyoKuala Lumpur

Singapore • Sydney

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IV

All rights reserved.No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic ormechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission inwriting from the publisher.

© Copyright 2013 by S. Karger AG, Basel (Switzerland)Distributed by S. Karger AG, Allschwilerstrasse 10, P.O. Box, CH-4009 Basel (Switzerland)ISBN: 978-3-318-02377-0e-ISBN: 978-3-318-02378-7

Library of Congress, Cataloging-in-Publication Data

Theilheimer’s synthetic methods of organic chemistry = Synthetische Methoden der organischen Chemie. –Vol. 81 (2013) - Basel; New York: Karger, © 1982 -v.Continues: Synthetic methods of organic chemistry.Editor: Gillian Tozer-Hotchkiss.1. Chemistry, Organic – yearbooks I. Tozer-Hotchkiss, Gillian II. Finch, Alan F. III. Theilheimer, William, 1914–2005ISBN: 978-3-318-02377-0e-ISBN: 978-3-318-02378-7

Deutsche AusgabenVol. 1 1946 1. Auflage

1948 2., unveränderte Auflage1950 3., unveränderte Auflage

Vol. 2 1948Vol. 3 1949 with English Index key

1953 2., unveränderte Auflage1966 3., unveränderte Auflage1975 4., unveränderte Auflage

Vol. 4 1950 with English Index key1966 2., unveränderte Auflage

English EditionsVol. 1 1948 Interscience Publishers

1975 (Karger) Second EditionVol. 2 1949 Interscience Publishers

1975 (Karger) Second EditionVol. 5 1951 with Cumulative Reaction Titles and Index

1966 Second EditionVol. 6 1952 1975 Second EditionVol. 7 1953 1975 Second EditionVol. 8 1954 1975 Second EditionVol. 9 1955Vol. 10 1956 with Cumulative Reaction Titles and Index

1975 Second EditionVol. 11 1957 1975 Second EditionVol. 12 1958 1975 Second EditionVol. 13 1959 1975 Second EditionVol. 14 1960 1975 Second EditionVol. 15 1961 with Cumulative Reaction Titles and IndexVol. 16 1962Vol. 17 1963Vol. 18 1964Vol. 19 1965Vol. 20 1966 with Cumulative Reaction Titles and IndexVol. 21 1967Vol. 22 1968Vol. 23 1969Vol. 24 1970Vol. 25 1971 with Cumulative Reaction Titles and IndexVol. 26 1972Vol. 27 1973Vol. 28 1974Vol. 29 1975Vol. 30 1976 with Cumulative Reaction Titles and IndexVol. 31 1977Vol. 32 1978Vol. 33 1979Vol. 34 1980

Vol. 35 1981 with Cumulative Reaction Titles and IndexVol. 36 1982Vol. 37 1983Vol. 38 1984Vol. 39 1985Vol. 40 1986 with Cumulative Reaction Titles and IndexVol. 41 1987Vol. 42 1988Vol. 43 1989Vol. 44 1990Vol. 45 1991 with Cumulative Reaction Titles and IndexVol. 46 1992Vol. 47 1993Vol. 48 1994Vol. 49 1995Vol. 50 1996 with Cumulative Reaction TitlesVol. 51 1997Vol. 52 1997Vol. 53 1998Vol. 54 1998Vol. 55 1999Vol. 56 1999Vol. 57 2000Vol. 58 2000Vol. 59 2001Vol. 60 2001Vol. 61 2002Vol. 62 2002Vol. 63 2003Vol. 64 2003Vol. 65 2004Vol. 66 2004Vol. 67 2005Vol. 68 2005Vol. 69 2006Vol. 70 2006Vol. 71 2007Vol. 72 2008Vol. 73 2008Vol. 74 2009Vol. 75 2009Vol. 76 2010Vol. 77 2011Vol. 78 2011Vol. 79 2012Vol. 80 2012

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V

Contents

Preface to Volume 81 ....................................................................... VI

Advice to the User ........................................................................... VIIGeneral Remarks ......................................................................... VIIMethods of Classification ........................................................... VIII

Further Trends and Developments in Synthetic Organic Chemistry

2012 .............................................................................................. XI

Systematic Survey ........................................................................... XXII

Abbreviations and Symbols ............................................................. XXIV

Reactions ......................................................................................... 1

Reviews............................................................................................ 480

Subject Index ................................................................................... 499

Supplementary References .............................................................. 556

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VI

Preface

This volume of Theilheimer contains abstracts of new synthetic methodsand supplementary data mainly from papers published in the literature up toMay 2012.

For browsing purposes, abstracts are displayed according to the SystematicClassification (symbol notation: summary p. VIII) so that reactions of thesame type and associated data appear together. For example, all deprotectionsappear in the early symbols (under HO32, HN32, HS32); reduction of oxocompds., imines and carbon-carbon multiple bonds under the HC8 sections;C-defunctionalization under the HC sections; oxy-functionalization underthe OC sections; aminations, nitrations, peptide coupling etc. under the NCsections; halogenation under the HalC sections; sulfurations under the SCsections; selenation, stannylation, phosphorylation, etc. under the RemCsections; syntheses involving C-C bond formation in the latter half of thebook under the CC sections; and data on resolutions (Res) at the end. A listof reaction symbols and references thereto is given in the Systematic Survey(p. XXII).

The displayed data are supported by the customary in-depth Subject Index(p. 499) and access to supplementary data can be made in the usual mannervia the Supplementary Reference section, e.g. the reader interested in updateson the Biginelli synthesis (Synth. Meth. 55, 337) will note from p. 559 thatadditional references can be found on p. 350 of this volume.

As usual, the volume contains a ‘Reviews’ section (p. 480), coveringreviews published up to and including November 2012, and a ‘Trends’ section(p. XI) incorporating key developments in synthetic chemistry up to andincluding November 2012.

I would like to express my gratitude to Alan Finch for his continuing helpand enthusiasm during the preparation of these volumes, as well as to JulianHayward and Chris Hardy. We are also very grateful for the assistance andsupport of Jill Entwistle, Eliot Cartwright-Finch, Chloë Cyrus-Kent and AndrewHotchkiss.

December 2012 G. Tozer-Hotchkiss, Editor

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Advice to the UserGeneral Remarks

New methods for the synthesis of organic compounds and improvementsof known methods are being recorded continuously in this series.

Reactions are classified on a simple though purely formal basis by symbols,which can be arranged systematically. Thus searches can be performedwithout knowledge of the current trivial or author names (e.g. ‘Oxidation’and ‘Friedel-Crafts reaction’).

Users accustomed to the common notations will find these in the subjectindex (see page 499). By consulting this index, use of the classificationsystem may be avoided. It is thought that the volumes should be kept closeat hand. The books should provide a quick survey, and obviate the immediateneed for an elaborate library search. Syntheses are therefore recorded in theindex by starting materials and end products, along with the systematicarrangement for the methods. This makes possible a sub-classification withinthe reaction symbols by reagents, a further methodical criterion. Complexcompounds are indexed with cross reference under the related simplercompounds. General terms, such as synthesis, replacement, heterocyclics,may also be brought to the attention of the reader.

A brief review, Trends and Developments in Synthetic Organic Chemistry(see page XI), stresses highlights of general interest and calls attention tokey methods too recent to be included in the body of the text.

The abstracts are limited to the information needed for an appraisal of theapplicability of a desired synthesis. In order to carry out a particular synthesisit is therefore advisable to have recourse to the original papers or, at least, toan abstract journal. In order to avoid repetition, selections are made on thebasis of most detailed description and best yields whenever the same methodis used in similar cases. Continuations of papers already included will notbe abstracted, unless they contain essentially new information. They may,however, be quoted at the place corresponding to the abstracted papers. Thesesupplementary references (see page 556) make it possible to keep abstractsof previous volumes up-to-date.

Syntheses that are divided into their various steps and recorded in differentplaces can be followed with the help of the notations such as startg. m. f.(starting material for the preparation of ...).

VII

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Advice to the User VIII

Method of Classification

Reaction Symbols. As summarized in the Systematic Survey (page XXII),reactions are classified firstly according to the bond formed in the synthesis,secondly according to the reaction type, and thirdly according to the bondbroken or the element eliminated. This classification is summarized in thereaction symbol, e.g

OC7N

The first part of the symbol refers to the chemical bond formed during thereaction, expressed as a combination of the symbols for the two elementsbonded together, e.g. HN, NC, CC. The order of the elements is as follows:

H, O, N, Hal (Halogen), S, Rem (Remaining elements), and C.

Thus, for the formation of a hydrogen-nitrogen bond, the notation is HN,not NH.

If two or more bonds are formed in a reaction, the ‘principle of the latestposition’ applies. Thus, for the reduction

RCH=O + H2 R CH-OHH

in which both hydrogen-oxygen and hydrogen-carbon bonds are formed,the symbol is HC8OC and not HO8OC.

The second part of the symbol refers to the reaction type. Four types aredistinguished: addition (8), rearrangement (1), exchange (6), and elimination(7), e.g.

RCH=CH2H2O R CH-CH3

OH+ OC8CC

SS SSCC1SC

R-Cl CN- R-CN+ [ + Cl- ] CC6Hal

R CH-CH3

Br

RCH=CH2[ + HBr ]

CC7Hal

Monomolecular reactions are either rearrangements (1), where themolecular weight of the starting material and product are the same, or

Bond formed Reactiontype

Bond broken orelement eliminated

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IX Advice to the User

eliminations (7), where an organic or inorganic fragment is lost; bimolecularand multicomponent reactions are either additions (8), such as intermolecularDiels-Alder reactions, Michael addition and 1,4-addition of organometallics,or exchanges (32), such as substitutions and condensations, where an organicor inorganic fragment is lost.

The last part of the symbol refers to the essential bond broken or, in thecase of exchange reactions and eliminations, to a characteristic fragmentwhich is lost. While the addition symbol is normally followed by the twoelements denoting the bond broken, in the case of valency expansion, whereno bonds are broken, the last part of the symbol indicates the atom at whichthe addition occurs, e.g.

R2S R2SO OS8S

RONO RONO2 ON8N

For addition, exchanges, and eliminations, the ‘principle of the latestposition’ again applies if more than one bond is broken. However, forrearrangements, the most descriptive bond-breakage is used instead. Thus,for the thio-Claisen rearrangement depicted above, the symbol is CC1SC,and not CC1CC.

Deoxygenations, quaternizations, stable radical formations, and certainrare reaction types are included as the last few methods in the yearbook. Thereaction symbols for these incorporate the special symbols El (electron pair),Het (heteropolar bond), Rad (radical), Res (resolutions), and Oth (otherreaction types), e.g.

R2S=O R2S EIS7O

R3N R'Cl R3N+R' Cl-+ Het8N

The following rules simplify the use of the reaction symbols:1. The chemical bond is rigidly classified according to the structural

formula without taking the reaction mechanism into consideration.2. Double or triple bonds are treated as being equivalent to two or three

single bonds, respectively.3. Only stable organic compounds are usually considered: intermediates

such as Grignard compounds and sodiomalonic esters, and inorganicreactants, such as nitric acid, are therefore not expressed in the reactionsymbols.

Reagents. A further subdivision, not included in the reaction symbols, isbased on the reagents used. The sequence of the reagents usually followsthat of the periodic system. Reagents made up of several components are

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Advice to the User X

arranged according to the element significant for the reaction (e.g. KMnO4

under Mn, NaClO under Cl). When a constituent of the reagent forms partof the product, the remainder of the reagent, which acts as a ‘carrier’ of thisconstituent, is the criterion for the classification; for example, phosphorus isthe carrier in a chlorination with PCl

5 and sodium in a nitrosation with NaNO

2.

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XI Trends

Further Trends and Developmentsin Synthetic Organic Chemistry 2012

In the coupling of organoboranes or organometallic reagents (Grignards,organozincs ...) with unsaturated halides the names of Suzuki, Kumada andNegishi instantly come to mind, and their methods continue to play a centralrole in modern synthetic chemistry. The downside is the inconvenience ofhandling unfriendly halides and preparing their reaction partners. ‘Direct’procedures by coupling unsaturated halides with arenes or alkenes havefollowed, largely inspired by Heck et al., and have been elaborated by related‘oxidative’ conversions, illustrated by palladium-catalyzed [hetero]biarylsyntheses based on coupling [hetero]arenes with arylboronic acids (cf.74, 516). Now an inexpensive iron-catalyzed procedure (with an iron-sulfurcluster complex and K2S2O8 as oxidant) is at hand1, as well as the novel gold-catalyzed coupling of arenes with arylsilanes (using PhI(OAc)2 as oxidant),where regioselectivity is determined largely by the electronic effect ofsubstituents rather than the more familiar placement of a directing group onthe arene2. A mild, inexpensive cobalt-catalyzed, N-directed ortho-couplingof 2-aryl-N-heteroarenes with aryl carbamates (sulfamates or phosphates) isa useful alternative to existing routes3, as is the unprecedented nickel-catalyzeddecarbonylative 2-arylation of azoles with phenyl benzoates4. Note, also, anunusual variant of Heck arylation wherein the intermediate arylpalladium(II)species are generated, not from the familiar aryl halides, but on ring closureof an o-acylstilbene with simultaneous formation of both a styrene and a1-naphthol derivative5. But even ‘direct’ arylation requires the readyavailability of functionalized arylating agent. Hence, the upsurge indehydrogenative Heck chemistry6 and dehydrogenative [hetero]arene coupling(CC32H) where neither of the reacting partners is functionalized, and wheredirecting groups and the choice of transition metal catalyst are often critical(cf. 72, 496s81). Here, the inexpensive copper-catalyzed C2-arylation ofindoles with 1,3-azoles (and air as terminal oxidant!) is a notable highlight,made possible by the placement of a readily removable pyrimidyl-directinggroup on indole nitrogen7. The Ru/Cu-catalyzed dehydrogenative o-vinylationof aryl carbamates with alkenes is notable for the incorporation of a removableO-directing group (again with air as oxidant)8, while a tandem Pd-catalyzedmethodology is based on in situ-dehydrogenative generation ofβ-functionalized enones (from the parent ketone) prior to dehydrogenativeα-vinylation or β-arylation9. In the same playing field is dehydrogenativeamination (NC32H), represented by a new copper-catalyzed coupling ofelectron-poor anilines with unactivated C-H bonds (using di-tert-butylperoxide as terminal oxidant)10. A mild, friendly, metal-free oxidative

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Trends XII

α-amination of aldehydes has also been reported, based on in situ-generationof hypoiodite as oxidant11, while N-direct o-amination of benzamides oraryl ketoximes can be effected without oxidant by denitrogenous couplingwith aryl azides under rhodium(III) catalysis12. More remarkable, however,is iron-catalyzed denitrogenous coupling of aryl azides with alkylarenesproviding diarylamines via C-cleavage of the alkyl group13.

Capturing the energy of the photon in a chemical reaction is as old as lifeitself, but incorporating this energy in a catalytic cycle through electrontransfer is rather special, and has led, arguably, to the emergence of themethodology of the moment: visible-light photoredox catalysis, throughwhich reactive intermediates (radicals, radical cations, iminium ions ...) canbe simply and efficiently generated14. The light-sensitive ruthenium(II)complex, Ru(bpy)3Cl2, has led the way as electron carrier with air as terminaloxidant, exemplified recently by the C-cleavage of 1,2-diamines with thesimultaneous generation of robust azomethinum ions and amine radicals15.Similarly, N-arylindoles are obtainable directly from o-styrylanilines viadehydrogenative coupling with [Ru(bpz)3](PF6)2 (where bpz = 2,2′-bipyraz-inyl) as electron carrier16, whereas [Ir(ppy)2(bpy)]PF6 facilitates Friedel-Craftsα-aminoalkylation with glycinamides via an oxygen-intercepted aminylcation and a Lewis acid-activated α-iminoacetamide17. By the same token,trifluoromethyl iodide can participate in the catalytic cycle with generationof a trifluoromethyl radical, leading to trifluoromethylarenes by subsequentcopper-catalyzed coupling with arylboronic acids18. The concept of visible-light photoredox asymmetric organocatalysis has also materialized, asrepresented by a mild, benign, metal-free enantioselective α-alkylation ofaldehydes with rose Bengal as catalytic sensitizer in the presence of a chiral4-oxazolidone19; photocatalytic intramolecular [2+2]-cycloaddition hasfeatured twice: in one instance with an iridium(III) polypyridyl complex ascatalyst, although here photosensitization is thought to involve energytransfer, rather than electron transfer20; in the other, however, molecularoxygen serves as redox catalyst in the presence of an antioxidant [BHT]21.Photoinduction of reactions by fluorescent light or with a mercury lamp isnot remarkable in itself, but the effect on classical copper-catalyzed UllmannN-arylation (and potentially other transition metal-catalyzed reactions) is soprofound as to suggest a quite distinct mechanistic scenario – possiblyinvolving photon-activation of the catalyst prior to single electron transferto the aryl halide22. UV-initiation of electron transfer within semiconductingtitanium dioxide has also been extended in decarboxylative C-alkylationand annulation with aliphatic carboxylic acids23.

Microporous metal-organic frameworks [MOFs] made headlines initially

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XIII Trends

in their capacity to store and separate small hydrocarbons24, but more recentlythey have come to the fore as reusable heterogeneous catalysts in the field ofliquid phase acid catalysis and aerobic oxidation25. Multifunctional MOFsbearing ordinarily incompatible active sites, have also emerged, as for examplethe MOF, PCN-124, which can effect one-pot deacetalation-Knoevenagelcondensation courtesy of active copper(II) sites and basic amide functionsattached to the organic framework26. Readily prepared silver(I)-containingMOFs with embedded chiral organocatalysts (e.g. cinchonine) have alsobeen designed for asymmetric [3+2]-cycloaddition with azomethine ylids27,while [returning to the field of visible-light photoredox catalysis] amine-functionalized zirconium(IV)-containing MOFs have proven to be highlyefficient and selective in aerobic reactions – seemingly bridging the gapbetween the classical transition metal-mediated and semiconducting protocolsas described above28.

Gold catalysis has lately escalated, as evident with abundant references inthe reviews literature29. Novel syntheses with gold nanoparticles are aparticular bonus30, and catalysis with ‘small gold clusters’ even more so.Here, cluster complexes with 3-10 gold atoms are reported to be astonishinglyactive in alkyne hydration with TON and TOF values of ca. 10 million and100,100/h, respectively31, while the recyclable ceria-supported gold-sulfurnanocluster complex, Au25(SR)18-on-CeO2, exhibits high activity in Ullmann-type homocoupling of aryl iodides32. In the field of asymmetric catalysis, anachiral gold(I) N-heterocyclic carbene [NHC] complex has been linked witha chiral 1,1′-binaphthyl-2,2′-diyl hydrogen phosphate in a new transfer-hydrogenation of quinolines, wherein both chiral anion and achiral NHCligand are central to high enantioselectivity at the 0.01 mol% level33. Inasymmetric transfer-hydrogenation of aliphatic ketones, however, a chiralsurfactant-tagged rhodium(III) 1,2-diamine complex is catalyst of choicefor a highly efficient and enantioselective conversion in water34. Chiralrhodium complexes have also been designed as artificial enzymes, and readily‘engineerable’ to maximize activity: here, a streptavidin-anchored complexwith a biotin bridge is both mild and active with tolerance of sensitivefunctional groups35, while a low-loading chiral cyclopentadienylrhodium(I)complex is remarkable in that the design leaves essential coordination siteson the metal open to effect asymmetric C-H bond functionalization36.Asymmetric [3+2]-cycloaddition with trimethylenemethane equivalents,however, benefits from the development of chiral bis(phosphorodiamidites)as ligand under the conventional palladium catalysis37.

With carbene chemistry one automatically defaults to rhodium-catalyzedreactions of diazo compounds where carbene insertion is still at a premium38,

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Trends XIV

and notably elaborated in a new pyridine synthesis from δ-diazoalkoximesvia intramolecular carbene insertion into N-O bonds39. Carbene transfer canalso be effected [from pre-formed or in situ-generated diazo compds.] withthe highly stable, electron-rich iron complex, Bu4N[Fe(CO)3(NO)], ascatalyst, the method being recently applied to a tandem allylic sulfenylation-Doyle-Kirmse reaction40. More significantly, however, are alternative non-metal procedures: in one, an organocatalyzed carbene insertion into N-Hbonds has been reported via activation of α-diazonitro compds. with ureas(and subsequent nucleophilic displacement of the nitro group)41; and inanother, reductive cleavage of the keto group in α-keto-esters generates anα-carbalkoxycarbenoid which effectively inserts into both N-H and O-Hbonds42. Developments in organometallic chemistry have been equallynotable. Thus, a veritable toolbox of alkyl- and fluoroalkyl-zinc sulfinates,impervious to impurities, is now available, notably useful for direct[fluoro]alkylation of N-heteroarenes43; a cobalt(II)-catalyzed carbozincationof alkynes has also been effected, thereby initiating a new stereoselectiveroute to tri- and tetra-substituted alkenes via vinylzinc compds.44, while noveliron(I) bis[o-di(phosphino)benzene] complexes have been devised for afriendly Negishi coupling45. The magnesium equivalent [Kumada coupling]is also in the news with the announcement of nickel-catalyzed coupling ofaliphatic or aromatic Grignard compounds with benzyl alcohols (rather thanthe customary, less convenient benzyl halides)46; so, too, an alternativestereoselective route to di- and tri-substituted (Z)-alkenes via vinylmagnesiumhalides, simply obtainable via FeCl2-catalyzed magnesiation of alkynes withethylmagnesium bromide47. In the sphere of organocopper(I) chemistry,ordinarily sensitive to moisture, it is now possible to effect classical 1,4-addition in water via Zn5Cu transmetalation in the presence of AuCl3 asLewis acid and TPGS-750-M as surfactant48; trifluoromethylation, of ever-increasing significance in pharmaceutical chemistry, has been elaboratedwith the simple generation of CuCF3 from fluoroform49, while the moreestablished trifluoromethylation with Me3SiCF3 has been adapted in a newsynthesis of α-(trifluoromethyl)- from α-diazo-esters50. In the arena of directfluorination, note, in particular, an efficient and general copper(I)-catalyzedfluorination of hydrocarbons with Selectfluor in the presence of N-hydroxy-phthalimide and an anionic phase transfer catalyst51, as well as a mildmanganese-catalyzed alternative with AgF/Bu4NF as fluorinating agent andiodosobenzene as oxidant52. The latter is potentially applicable to the rapidpreparation of medicinally important 18F-labelled fluorides, although a simplenickel-mediated oxidative route with aqueous 18F-fluoride ion, achievablein seconds, is already in the media53.

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XV Trends

Cooperative and bifunctional catalysis are a small subset of catalysis ingeneral, and each enjoying diversification. With the first, note especiallyasymmetric condensations of enals with activated ketones where the formeris activated by a chiral NHC (à la Stetter) while a Lewis acid cooperates byactivation of the ketone54; on the other hand, asymmetric α-vinylation ofaldehydes is effected by classical activation of the latter with a chiral amine(à la aldol condensation) while the copper catalyst facilitates the subsequentvinylation with a vinyliodonium triflate55. Bifunctional catalysis withderivatized MOFs has already been highlighted, inspired no doubt by theactivity of functionalized mesoporous silicas, such as chiral amine-graftedSBA-15, with which an asymmetric Henry reaction-Michael addition hasbeen realized via amine-activation of the starting aldehyde and supported byacidic hydroxylic sites on the silica surface56. Chiral bifunctional bis(ureas)are also notable in this respect, as reflected in a formal carbonyl-ene reactionwith formaldehyde tert-butylhydrazone, where one of the urea residuesactivates the carbonyl partner via hydrogen bonding with N-H bonds whilethe hydrazone group is activated by hydrogen bonding to the carbonyl groupof the second urea residue57.

Remote functionalization is ordinarily difficult to effect cleanly, efficientlyand with high selectivity. However, palladium catalysis has come to therescue (yet again!) in various contexts: thus, N-protected α-amino-esterswith unfunctionalized alkyl chains can be arylated at the terminal site (up tothe ζ-site) in the presence of a lithium amide58, while β-arylation of carboxylicacid amides can be achieved with Pd(OCOCF3)2 ligated to 2-isobutoxy-quinoline as directing ligand59. Remote control of an asymmetric Heckarylation has also been recorded under palladium catalysis with a bulky (∆2-oxazo-lin-2-yl)pyridine as chiral ligand, wherein a homoallyl alcohol is convertedto a chiral γ-aryloxo compound via a palladium migration along the chain60.

In catalysis, chemoselectivity issues invariably prevail in one shapeor another. Ligand effects can be significant but homing in on the optimumone for a given transformation can be matter of chance. However, for peptide-mediated epoxidation at the allylic site of a polyenol [with carbodiimide/H2O2], a combinatorial assay of various peptides quickly revealed theimportance of an Asp residue in dictating the desired regioselectivity61. Thenature of a catalytic support can also be critical. Thus, gold nanoparticles-on-NiO selectively catalyze the oxidation of primary alcohols to carboxylicacids in water, while carboxylic acid esters are obtained uniquely with CeO2

as support62. Remarkedly, the oxidation of benzyl alcohols on TiO2 can beentirely shape-dependent. Here, the trick is to cover the oxide surface with aporous layer of alumina and create holes of a particular size to permit (or

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Trends XVI

prevent) substrates reaching the TiO2 surface63. Solvent, too, is often at apremium, as evident in Lewis acid-catalyzed aldol-type condensations with2-siloxyfurans, where aqueous media favor classical substitution at C2 whiledry media effect vinylogous aldol-type condensation64; solvent-dictatedchemoselectivity has also been observed with Kumada coupling of Grignardreagents with tosylhydrazones: cyclohexane favoring classical coupling, whileTHF alters the course to provide alkenes for the first time65. Interestingly,alkene synthesis from tosylhydrazones has also been forged under metal-free conditions by coupling with α,β-ethyleneboronic acids in the presenceof base66, while a metal-free ‘click’ synthesis of 1,2,3-triazoles has beenrealized by simply coupling α,α-dichlorinated tosylhydrazones with primaryamines67,67a.

In conclusion, a few recent highlights: palladium-catalyzed 1,4-additionof arylsulfinic acids68, supplementing the gathering arsenal of desulfitativeconversions69; further novel syntheses with DMF, such as iron-catalyzedoxidative methylenation of heteroaromatic methyl groups70; metal-free1,4-addition of cyanide ion, generated by C-cleavage of malononitrile71, andcopper-catalyzed N-directed oxidative o-cyanation based on initial oxidativeC-cleavage of benzyl cyanide72; alternative, eco-friendly aromatizing routesto phenolethers and aniline derivs. from 2-cyclohexenones73; furtherdevelopments in flow chemistry, with particular reference to combining flowreactions with continuous product purification74, and the prospect of includingmicrowave enhancement in flow75; in the field of mechanochemistry, ball-milling has been usefully adapted in an eco-friendly and clean carbodiimide-mediated amidation (avoiding preactivation of the reactants)76, and as an aidto optical resolution by co-crystallization77; and the emergence of ‘covalent’mechanochemistry where polymer-tagged reactants can be effectivelycontorted under ultrasonication to deliver anomalous reactivity: even ‘click’cycloaddition can be reversed by this technique!!78.

1 J. Wang, S. Wang, G. Wang, J. Zhang, X.-Q. Yu, Chem. Commun. 2012, 48 (96), 11769-71[DOI: 10.1039/c2cc35468c].

2 L.T. Ball, G.C. Lloyd-Jones, C.A. Russell, Science 2012, 337 (6102), 1644-8 [DOI: 10.1126/science.1225709]; for a review on non-directed C-H activation of arenes s. N. Kuhl, M.N.Hopkinson, J. Wencel-Delord, F. Glorius, Angew. Chem., Int. Ed. 2012, 51 (41), 10236-54[DOI: 10.1002/anie.201203269]; for the palladium-catalyzed m-directed arylation of electron-deficient arenes with aryl bromides s. Y.-N. Wang, X.-Q. Guo, X.-H. Zhu, R. Zhong, L.-H.Cai, X.-F. Hou, Chem. Commun. 2012, 48 (84), 10437-9 [DOI: 10.1039/c2cc34949c].

3 W. Song, L. Ackermann, Angew. Chem., Int. Ed. 2012, 51 (33), 8251-4 [DOI: 10.1002/anie.201202466].

4 K. Amaike, K. Muto, J. Yamaguchi, K. Itami, J. Am. Chem. Soc. 2012, 134 (33), 13573-6[DOI: 10.1021/ja306062c].

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5 S.W. Youn, B.S. Kim, A.R. Jagdale, J. Am. Chem. Soc. 2012, 134 (28), 11308-11 [DOI: 10.1021/ja304616q].

6 For palladium-catalyzed (Z)-selective dehydrogenative β-arylation of enacylamines s. S.Pankajakshan, Y.-H. Xu, J.K. Cheng, M.T. Low, T.-P. Loh, Angew. Chem., Int. Ed. 2012, 51(23), 5701-5 [DOI: 10.1002/anie.201109247]; for ruthenium- or rhodium-catalyzeddehydrogenative β-vinylation of α,β-ethylenecarboxamides s. J. Zhang, T.-P. Loh, Chem.Commun. 2012, 48 (91), 11232-4 [DOI: 10.1039/c2cc36137j]; for the rhodium-catalyzeddehydrogenative coupling of alkenes with aldehydes via activation of the formyl C-H bond s.Z. Shi, N. Schröder, F. Glorius, Angew. Chem., Int. Ed. 2012, 51 (32), 8092-6 [DOI: 10.1002/anie.201203224].

7 M. Nishino, K. Hirano, T. Satoh, M. Miura, Angew. Chem., Int. Ed. 2012, 51 (28), 6993-7[DOI: 10.1002/anie.201201491].

8 J. Li, C. Kornhaaß, L. Ackermann, Chem. Commun. 2012, 48 (92), 11343-5 [DOI: 10.1039/c2cc36196e]; for an example of using an in situ-generated, recyclable N-directing group s.Z. Wang, B.J. Reinus, G. Dong, J. Am. Chem. Soc. 2012, 134 (34), 13954-7 [DOI: 10.1021/ja306123m].

9 Y. Moon, D. Kwon, S. Hong, Angew. Chem., Int. Ed. 2012, 51 (45), 11333-6 [DOI: 10.1002/anie.201206610].

10 R.T. Gephart III, D.L. Huang, M.J.B. Aguila, G. Schmidt, A. Shahu, T.H. Warren, Angew.Chem., Int. Ed. 2012, 51 (26), 6488-92 [DOI: 10.1002/anie.201201921]; for the copper-catalyzed synthesis of acridones by dehydrogenative intramolecular o-arylamination s. W. Zhou,Y. Liu, Y. Yang, G.-J. Deng, Chem. Commun. 2012, 48 (86), 10678-80 [DOI: 10.1039/c2cc35425j].

11 J.-S. Tian, K.W.J. Ng, J.-R. Wong, T.-P. Loh, Angew. Chem., Int. Ed. 2012, 51 (36), 9105-9[DOI: 10.1002/anie.201204215].

12 J. Ryu, K. Shin, S.H. Park, J.Y. Kim, S. Chang, Angew. Chem., Int. Ed. 2012, 51 (39), 9904-8[DOI: 10.1002/anie.201205723]; for rhodium-catalyzed o-directed sulfonylamination withsulfonyl azides s. J.Y. Kim, S.H. Park, J. Ryu, S.H. Cho, S.H. Kim, S. Chang, J. Am. Chem.Soc. 2012, 134 (22), 9110-3 [DOI: 10.1021/ja303527m]; for palladium-catalyzed o-carbalkoxy-amination of lithium benzoates s. K.-H. Ng, F.-N. Ng, W.-Y. Yu, Chem. Commun. 2012, 48(95), 11680-2 [DOI: 10.1039/c2cc36502b].

13 C. Qin, T. Shen, C. Tang, N. Jiao, Angew. Chem., Int. Ed. 2012, 51 (28), 6971-5 [DOI: 10.1002/anie.201202464].

14 Review s. J. Xuan, W.-J. Xiao, Angew. Chem., Int. Ed. 2012, 51 (28), 6828-38 [DOI: 10.1002/anie.201200223]; s.a. the Reviews Section 18 (p. 496).

15 S. Cai, X. Zhao, X. Wang, Q. Liu, Z. Li, D.Z. Wang, Angew. Chem., Int. Ed. 2012, 51 (32),8050-3 [DOI: 10.1002/anie.201202880].

16 S. Maity, N. Zheng, Angew. Chem., Int. Ed. 2012, 51 (38), 9562-6 [DOI: 10.1002/anie.201205137]; for indole synthesis by palladium-catalyzed dehydrogenative ring closureof N-arylazomethines s. Z. Shi, F. Glorius, ibid. 2012, 51 (37), 9220-2 [DOI: 10.1002/anie.201205079]; s.a. Y. Wei, I. Deb, N. Yoshikai, J. Am. Chem. Soc. 2012, 134 (22), 9098-101 [DOI: 10.1021/ja3030824]; by a 3-component synthesis under dual palladium catalysisfrom o-dihalides, ketones and prim. amines s. J.M. Knapp, J.S. Zhu, D.J. Tantillo, M.J. Kurth,Angew. Chem., Int. Ed. 2012, 51 (42), 10588-91 [DOI: 10.1002/anie.201204633].

17 S. Zhu, M. Rueping, Chem. Commun. 2012, 48 (98), 11960-2 [DOI: 10.1039/c2cc36995h].18 Y. Ye, M.S. Sanford, J. Am. Chem. Soc. 2012, 134 (22), 9034-7 [DOI: 10.1021/ja301553c].19 K. Fidaly, C. Ceballos, A. Falguières, M.S.-I. Veitia, A. Guy, C. Ferroud, Green Chem. 2012

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20 Z. Lu, T.P. Yoon, Angew. Chem., Int. Ed. 2012, 51 (41), 10329-32 [DOI: 10.1002/anie.201204835].

21 D.P. Kranz, A.G. Griesbeck, R. Alle, R. Perez-Ruiz, J.M. Neudörfl, K. Meerholz, H.-G. Schmalz,Angew. Chem., Int. Ed. 2012, 51 (24), 6000-4 [DOI: 10.1002/anie.201201222].

22 S.E. Creutz, K.J. Lotito, G.C. Fu, J.C. Peters, Science 2012, 338 (6107), 647-51 [DOI: 10.1126/science.1226458].

23 D.W. Manley, R.T. McBurney, P. Miller, R.F. Howe, S. Rhydderch, J.C. Walton, J. Am. Chem.Soc. 2012, 134 (33), 13580-3 [DOI: 10.1021/ja306168h].

24 Review s. Y. He, W. Zhou, R. Krishna, B. Chen, Chem. Commun. 2012, 48 (97), 11813-31[DOI: 10.1039/c2cc35418g].

25 Review s. A. Dhakshinamoorthy, M. Alvaro, H. Garcia, Chem. Commun. 2012, 48 (92), 11275-88 [DOI: 10.1039/c2cc34329k].

26 J. Park, J.-R. Li, Y.-P. Chen, J. Yu, A.A. Yakovenko, Z.U. Wang, L.-B. Sun, P.B. Balbuena,H.-C. Zhou, Chem. Commun. 2012, 48 (80), 9995-7 [DOI: 10.1039/c2cc34622b].

27 X. Jing, C. He, D. Dong, L. Yang, C. Duan, Angew. Chem., Int. Ed. 2012, 51 (40), 10127-31[DOI: 10.1002/anie.201204530].

28 J. Long, S. Wang, Z. Ding, S. Wang, Y. Zhou, L. Huang, X. Wang, Chem. Commun. 2012, 48(95), 11656-8 [DOI: 10.1039/c2cc34620f]; for the visible-light photocatalytic activity of a zinc-containing porphyrin-type MOF as used for the sacrificial hydrogen evolution from water s.A. Fateeva, P.A. Chater, C.P. Ireland, A.A. Tahir, Y.Z. Khimyak, P.V. Wiper, J.R. Darwent, M.J.Rosseinsky, Angew. Chem., Int. Ed. 2012, 51 (30), 7440-4 [DOI: 10.1002/anie.201202471].

29 For recent review literature on gold catalysis s. Reviews Section 4 (p. 482)30 For recent review literature on gold nanoparticles s. Reviews Section 3 (p. 482)31 J. Oliver-Meseguer, J.R. Cabrero-Antonino, I. Domínguez, A. Leyva-Pérez, A. Corma, Science

2012, 338 (6113), 1452-5 [DOI: 10.1126/science.1227813]; preparation of NHC-ligated trigoldcluster complexes s. T.J. Robilotto, J. Bacsa, T.G. Gray, J.P. Sadighi, Angew. Chem., Int. Ed.2012, 51 (48), 12077-80 [DOI: 10.1002/anie.201206712].

32 G. Li, C. Liu, Y. Lei, R. Jin, Chem. Commun. 2012, 48 (98), 12005-7 [DOI: 10.1039/c2cc34765b];for the catalytic activity gold nanoparticles-on-TiO2 in the dehydrogenative solvolysis ofdisilanes s. C. Gryparis, M. Stratakis, ibid. 48 (87), 10751-3 [DOI: 10.1039/c2cc35116a].

33 X.-F. Tu, L.-Z. Gong, Angew. Chem., Int. Ed. 2012, 51 (45), 11346-9 [DOI: 10.1002/anie.201204179].

34 J. Li, Y. Tang, Q. Wang, X. Li, L. Cun, X. Zhang, J. Zhu, L. Li, J. Deng, J. Am. Chem. Soc.2012, 134 (45), 18522-5 [DOI: 10.1021/ja308357y].

35 T.K. Hyster, L. Knörr, T.R. Ward, T. Rovis, Science 2012, 338 (6106), 500-3 [DOI: 10.1126/science.1226132]; for a one-pot chemoenzymatic cascade synthesis promoted sequentiallyby an enzyme and a streptavidin-protected iridium complex s. V. Köhler, Y.M. Wilson, M.Dürrenberger, D. Ghislieri, E. Churakova, T. Quinto, L. Knörr, D. Häussinger, F. Hollmann,N.J. Turner, T.R. Ward, Nat. Chem. 2013, 5 (2), 93-9 [DOI: 10.1038/nchem.1498].

36 B. Ye, N. Cramer, Science 2012, 338 (6106), 504-6 [DOI: 10.1126/science.1226938].37 B.M. Trost, T.M. Lam, J. Am. Chem. Soc. 2012, 134 (28), 11319-21 [DOI: 10.1021/ja305717r].38 For a recent reference to rhodium(II)-catalyzed o-directed carbene insertions s. W.-W. Chan,

S.-F. Lo, Z. Zhou, W.-Y. Yu, J. Am. Chem. Soc. 2012, 134 (33), 13565-8 [DOI: 10.1021/ja305771y].

39 X. Qi, L. Dai, C.-M. Park, Chem. Commun. 2012, 48 (91), 11244-6 [DOI: 10.1039/c2cc36009h];for a new pyridine synthesis from N-allylynamines s. W. Gati, M.M. Rammah, M.B. Rammah,F. Couty, G. Evano, J. Am. Chem. Soc. 2012, 134 (22), 9078-81 [DOI: 10.1021/ja303002a].

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40 M.S. Holzwarth, I. Alt, B. Plietker, Angew. Chem., Int. Ed. 2012, 51 (22), 5351-4 [DOI: 10.1002/anie.201201409].

41 S.S. So, A.E. Mattson, J. Am. Chem. Soc. 2012, 134 (21), 8798-801 [DOI: 10.1021/ja3031054].42 E.J. Miller, W. Zhao, J.D. Herr, A.T. Radosevich, Angew. Chem., Int. Ed. 2012, 51 (42), 10605-

9 [DOI: 10.1002/anie.201205604].43 Y. Fujiwara, J.A. Dixon, F. O′Hara, E.D. Funder, D.D. Dixon, R.A. Rodriguez, R.D. Baxter,

B. Herlé, N. Sach, M.R. Collins, Y. Ishihara, Nature 2012, 492 (7427), 95-9 [DOI: 10.1038/nature11680].

44 M. Corpet, C. Gosmini, Chem. Commun. 2012, 48 (94), 11561-3 [DOI: 10.1039/c2cc36676b].45 C.J. Adams, R.B. Bedford, E. Carter, N.J. Gower, M.F. Haddow, J.N. Harvey, M. Huwe, M.Á.

Cartes, S.M. Mansell, C. Mendoza, D.M. Murphy, E.C. Neeve, J. Nunn, J. Am. Chem. Soc.2012, 134 (25), 10333-6 [DOI: 10.1021/ja303250t].

46 D.-G. Yu, X. Wang, R.-Y. Zhu, S. Luo, X.-B. Zhang, B.-Q. Wang, L. Wang, Z.-J. Shi, J. Am.Chem. Soc. 2012, 134 (36), 14638-41 [DOI: 10.1021/ja307045r].

47 L. Ilies, T. Yoshida, E. Nakamura, J. Am. Chem. Soc. 2012, 134 (41), 16951-4 [DOI: 10.1021/ja307631v].

48 B.H. Lipshutz, S. Huang, W.W.Y. Leong, G. Zhong, N.A. Isley, J. Am. Chem. Soc. 2012, 134(49), 19985-8 [DOI: 10.1021/ja309409e].

49 For the synthesis of α-(trifluoromethyl)ketones s. P. Novák, A. Lishchynskyi, V.V. Grushin,J. Am. Chem. Soc. 2012, 134 (39), 16167-70 [DOI: 10.1021/ja307783w]; for recent reviewsof trifluoromethylation s. the Reviews Section 6 (p. 484); for copper-catalyzed asymmetricα-(trifluoromethyl)ation of β-keto-esters s. Q.-H. Deng, H. Wadepohl, L.H. Gade, ibid. 134(26), 10769-72 [DOI: 10.1021/ja3039773]

50 M. Hu, C. Ni, J. Hu, J. Am. Chem. Soc. 2012, 134 (37), 15257-60 [DOI: 10.1021/ja307058c].51 S. Bloom, C.R. Pitts, D.C. Miller, N. Haselton, M.G. Holl, E. Urheim, T. Lectka, Angew.

Chem., Int. Ed. 2012, 51 (42), 10580-3 [DOI: 10.1002/anie.201203642].52 W. Liu, X. Huang, M.-J. Cheng, R.J. Nielsen, W.A. Goddard III, J.T. Groves, Science 2012, 337

(6100), 1322-5 [DOI: 10.1126/science.1222327]; for the synthesis of fluorides by iron-catalyzedradical hydrofluorination of alkenes s. T.J. Barker, D.L. Boger, J. Am. Chem. Soc. 2012, 134(33), 13588-91 [DOI: 10.1021/ja3063716]; for a silver-catalyzed decarboxylative synthesis offluorides s. F. Yin, Z. Wang, Z. Li, C. Li, ibid. 134 (25), 10401-4 [DOI: 10.1021/ja3048255]; fornucleophilic fluorination of diazo compds. with HBF4 s. R. Pasceri, H.E. Bartrum, C.J. Hayes,C.J. Moody, Chem. Commun. 2012, 48 (99), 12077-9 [DOI: 10.1039/c2cc37284c].

53 E. Lee, J.M. Hooker, T. Ritter, J. Am. Chem. Soc. 2012, 134 (42), 17456-8 [DOI: 10.1021/ja3084797]; alternative method for the synthesis of 18F-labelled 4-fluorophenols s. Z. Gao,Y.H. Lim, M. Tredwell, L. Li, S. Verhoog, M. Hopkinson, W. Kaluza, T.L. Collier, J. Passchier,M. Huiban, V. Gouverneur, Angew. Chem., Int. Ed. 2012, 51 (27), 6733-7 [DOI: 10.1002/anie.201201502].

54 For the asymmetric synthesis of oxindole-based spirocyclic γ-lactones s. J. Dugal-Tessier,E.A. O′Bryan, T.B.H. Schroeder, D.T. Cohen, K.A. Scheidt, Angew. Chem., Int. Ed. 2012, 51(20), 4963-7 [DOI: 10.1002/anie.201201643]; of trifluoromethylated α,β-ethylene-δ-lactoness. J. Mo, X. Chen, Y.R. Chi, J. Am. Chem. Soc. 2012, 134 (21), 8810-3 [DOI: 10.1021/ja303618z].

55 E. Skucas, D.W.C. MacMillan J. Am. Chem. Soc. 2012, 134 (22), 9090-3 [DOI: 10.1021/ja303116v]; for the asymmetric dehydrogenative α-vinylation of tert. amines by the samemethodology s. G. Zhang, Y. Ma, S. Wang, Y. Zhang, R. Wang, ibid. 134 (30), 12334-7 [DOI:10.1021/ja303333k]

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56 S. Yang, J. He Chem. Commun. 2012, 48 (83), 10349-51 [DOI: 10.1039/c2cc35110b].57 A. Crespo-Peña, D. Monge, E. Martín-Zamora, E. Álvarez, R. Fernández, J.M. Lassaletta,

J. Am. Chem. Soc. 2012, 134 (31), 12912-5 [DOI: 10.1021/ja305209w].58 S. Aspin, A.-S. Goutierre, P. Larini, R. Jazzar, O. Baudoin, Angew. Chem., Int. Ed. 2012, 51

(43), 10808-11 [DOI: 10.1002/anie.201206237].59 M. Wasa, K.S.L. Chan, X.-G. Zhang, J. He, M. Miura, J.-Q. Yu, J. Am. Chem. Soc. 2012, 134

(45), 18570-2 [DOI: 10.1021/ja309325e].60 E.W. Werner, T.-S. Mei, A.J. Burckle, M.S. Sigman, Science 2012, 338 (6113), 1455-8 [DOI:

10.1126/science.1229208]; for an interesting palladium migration in the allylic cross-couplingof homoallylic electrophiles with arylboronic acids s. B.J. Stokes, S.M. Opra, M.S. Sigman,J. Am. Chem. Soc. 2012, 134 (28), 11408-11 [DOI: 10.1021/ja305403s].

61 P.A. Lichtor, S.J. Miller, Nat. Chem. 2012, 4 (12), 990-5 [DOI: 10.1038/nchem.1469].62 T. Ishida, Y. Ogihara, H. Ohashi, T. Akita, T. Honma, H. Oji, M. Haruta, ChemSusChem 2012,

5 (11), 2243-8 [DOI: 10.1002/cssc.201200324].63 C.P. Canlas, J. Lu, N.A. Ray, N.A. Grosso-Giordano, S. Lee, J.W. Elam, R.E. Winans, R.P. Van

Duyne, P.C. Stair, J.M. Notestein, Nat. Chem. 2012, 4 (12), 1030-6 [DOI: 10.1038/nchem.1477].64 M. Woyciechowska, G. Forcher, S. Buda, J. Mlynarski, Chem. Commun. 2012, 48 (89), 11029-

31 [DOI: 10.1039/c2cc36656h].65 J.-C. Wu, L.-B. Gong, Y. Xia, R.-J. Song, Y.-X. Xie, J.-H. Li, Angew. Chem., Int. Ed. 2012, 51

(39), 9909-13 [DOI: 10.1002/anie.201205969].66 M.C. Pérez-Aguilar, C. Valdés Angew. Chem., Int. Ed. 2012, 51 (24), 5953-7 [DOI: 10.1002/

anie.201200683].67 S.S. van Berkel, S. Brauch, L. Gabriel, M. Henze, S. Stark, D. Vasilev, L.A. Wessjohann,

M. Abbas, B. Westermann, Angew. Chem., Int. Ed. 2012, 51 (22), 5343-6 [DOI: 10.1002/anie.201108850]; for the direct synthesis of azides from tosylhydrazones, and application tothe direct conversion of oxo compds. to 1,2,3-triazoles s. J. Barluenga, M. Tomás-Gamasa,C. Valdés, ibid. 51 (24), 5950-2 [DOI: 10.1002/anie.201200313].

68 H. Wang, Y. Li, R. Zhang, K. Jin, D. Zhao, C. Duan, J. Org. Chem. 2012, 77 (10), 4849-53[DOI: 10.1012/jo300654s].

69 Recent methods s. 80, 463s81; for the direct palladium-catalyzed substitution of allylic prim-amino groups by Na-sulfinates to give β,γ-ethylenesulfones (with retention of configuration)s. X.-S. Wu, Y. Chen, M.-B. Li, M.-G. Zhou, S.-K. Tian, J. Am. Chem. Soc. 2012, 134 (36),14694-7 [DOI: 10.1021/ja306407x].

70 S.-J. Lou, D.-Q. Xu, D.-F. Shen, Y.-F. Wang, Y.-K. Liu, Z.-Y. Xu, Chem. Commun. 2012, 48(98), 11993-5 [DOI: 10.1039/c2cc36708d]; for a metal-free synthesis of α-ketocarboxamidesfrom methyl ketones with formamides s. W.-P. Mai, H.-H. Wang, Z.-C. Li, J.-W. Yuan, Y.-M.Xiao, L.-R. Yang, P. Mao, L.-B. Qu, ibid. 48 (81), 10117-9 [DOI: 10.1039/c2cc35279f]; for areview of syntheses with DMF s. the Reviews Section 19 (p. 496).

71 S. Lin, Y. Wei, F. Liang, Chem. Commun. 2012, 48 (79), 9879-81 [DOI: 10.1039/c2cc35528k].72 J. Jin, Q. Wen, P. Lu, Y. Wang, Chem. Commun. 2012, 48 (79), 9933-5 [DOI: 10.1039/

c2cc35046g].73 For the copper-catalyzed formation of phenolethers s. M.-O. Simon, S.A. Girard, C.-J. Li,

Angew. Chem., Int. Ed. 2012, 51 (30), 7537-40 [DOI: 10.1002/anie.201200698]; of anilinesand p-iodoanilines s. M.T. Barros, S.S. Dey, C.D. Maycock, P. Rodrigues, Chem. Commun.2012, 48 (88), 10901-3 [DOI: 10.1039/c2cc35801h].

74 A.G. O′Brien, Z. Horváth, F. Lévesque, J.W. Lee, A. Seidel-Morgenstern, P.H. Seeberger,Angew. Chem., Int. Ed. 2012, 51 (28), 7028-30 [DOI: 10.1002/anie.201202795].

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75 For an overview of laboratory applications of microwave reactors s. S.K. Ritter, Chem. Eng.News 2012, 90 (39), 32-4.

76 V. Štrukil, B. Bartolec, T. Portada, I. Dilovic, I. Halasz, D. Margetic, Chem. Commun. 2012,48 (99), 12100-2 [DOI: 10.1039/c2cc36613d]; s.a. T.-X. Métro, J. Bonnamour, T. Reidon,J. Sarpoulet, J. Martinez, F. Lamaty, ibid. 48 (96), 11781-3 [DOI: 10.1039/c2cc36352f].

77 M.D. Eddleston, M. Arhangelskis, T. Frišcic, W. Jones, Chem. Commun. 2012, 48 (92), 11340-2 [DOI: 10.1039/c2cc36130b].

78 For an overview of covalent mechanochemistry s. B. Halford, Chem. Eng. News 2012, 90(40), 55-7.

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Systematic Survey

OC8C 45

OC8CC 45

OC1HC 55

OC1CC 56

OC32H 58

OC32O 66

OC32N 70

OC32Hal 73

OC32S 75

OC32Rem 76

OC32C 77

OC7H 83

OC7O 88

OC7N 91

OC7Hal 92

OC7Rem 93

OC7C 93

NN32H 94

NC8HN 95

NC8ON 95

NC8OC 95

NC8NN 97

NC8NC 98

NC8CC 100

NC1HC 111

NC1ON 112

NC1CC 112

NC32H 116

NC32O 126

NC32N 144

NC32Hal 149

NC32S 158

NC32Rem 159

NC32C 162

NC7H 166

NC7O 171

NC7N 174

NC7Hal 175

NC7S 176

NC7C 176

HalS32H 177

HalS32O 177

HalS32Hal 177

HalS32S 177

HalC8NC 178

HalC8CC 178

HalC1CC 181

HalC32H 182

HalC32O 187

HalC32N 189

HalC32Hal 189

HalC32S 189

HalC32Rem 191

HalC32C 191

SS32H 193

SRem32H 194

SC8NC 195

SC8CC 195

SC32H 198

SC32O 199

SC32N 201

SC32Hal 202

SC32S 206

SC32Rem 208

Reaction symbol Page

HO32Rem 1

HO32C 2

HN32O 4

HN32N 7

HN32C 8

HC8OC 10

HC8NC 16

HC8CC 18

HC32O 26

HC32N 29

HC32Hal 30

HC32S 31

HC32Rem 31

HC7O 32

HC7N 33

HC7C 34

OO8CC 35

ON8N 35

OS8S 35

ORem8HRem 37

ORem8OC 37

ORem8Rem 38

ORem32O 38

ORem32N 39

ORem32Hal 40

ORem32C 40

OC8HC 41

OC8ON 42

OC8OC 42

OC8NC 44

XXII

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Reaction symbol Page

SC32C 209

SC7H 209

SC7C 210

RemC8OC 211

RemC8NC 211

RemC8CC 212

RemC1CC 215

RemC32H 216

RemC32O 218

RemC32N 219

RemC32Hal 219

RemC32S 221

RemC32Rem 221

RemC32C 226

RemC7H 227

RemC7C 227

CC8HC 227

CC8OC 228

CC8NC 241

CC8SC 252

CC8RemC 252

CC8C 253

CC8CC 253

CC1HC 306

CC1OC 315

CC1NS 321

CC1NC 321

CC1SC 323

CC1CC 324

CC32H 326

XXIII Systematic Survey

CC32O 343

CC32N 377

CC32Hal 388

CC32S 415

CC32Rem 420

CC32C 450

CC7H 464

CC7O 466

CC7N 468

CC7Hal 470

CC7Rem 475

CC7C 476

ElS7O 477

ElRem7O 477

Res 478

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XXIV

Abbreviations and Symbols

abs. ............................................................ absolutealc. ............................................................ alcoholicaq. ............................................................. aqueousar. .............................................................. aromaticatm. ........................................................... atmosphere(s)compd(s). .................................................. compound(s)deriv(s). .................................................... derivative(s)e.e. ............................................................ enantiomeric excesseq(s). ......................................................... equivalent(s)E. ............................................................... ExampleF.e.s. .......................................................... Further example(s) seeM ............................................................... molarprepn. ........................................................ preparationprim. ......................................................... primarys80 ............................................................ supplementary reference in Volume 81sec. ............................................................ secondarystartg. m.f. ................................................ starting material for (the preparation of …)subst. ......................................................... substitutedsym. .......................................................... symmetricaltert. ........................................................... tertiaryv.i. ............................................................. via intermediatesw.a.r. ......................................................... without additional reagentsY * ............................................................ Yield

E .............................................................. ElectrolysisI .............................................................. Irradiation[\\\\] ........................................................... Microwave irradiationB .............................................................. Ring closureC .............................................................. Ring contractionD .............................................................. Ring expansionF .............................................................. Ring openingG .............................................................. Ring hydrogenation4 .............................................................. ‘see title or reagent on the left half of the page’

* Yields in parentheses refer to the immediately preceding step of a multi-step reaction

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