Organolithiums: Selectivity for Synthesis

by Clayden

• ISBN13: 9780080432618
• ISBN10: 0080432611
• Edition: 1st
• Format: Paperback
• Copyright: 2002-07-12
• Publisher: Elsevier Science

Summary

This book, Volume 23 in the Tetrahedron Organic Chemistry series, presents organolithium chemistry from the perspective of a synthetic organic chemist, drawing from the synthetic literature to present a unified overview of how organolithiums can be used to make molecules. The development of methods for the regioselective synthesis of organolithiums has replaced their image of indiscriminate high reactivity with one of controllable and subtle selectivity. Organolithium chemistry has a central role in the selective construction of C-C bonds in both simple and complex molecules, and for example has arguably overtaken aromatic electrophilic substitution as the most powerful method for regioselective functionalisation of aromatic rings. The twin themes of reactivity and selectivity run through the book, which reviews the ways by which organolithiums may be formed and the ways in which they react. Topics include recent advances in directed metallation, reductive lithiation and organ

Table of Contents

Foreword	xi
Acknowledgements	xiii
Abbreviations	xv
Introduction	1	(8)
Scope and overview	1	(1)
Organolithiums in solution	2	(7)
References	7	(2)
Regioselective Synthesis of Organolithiums by Deprotonation	9	(102)
General points	9	(1)
Lithiation α to heteroatoms	10	(18)
Lithiation α to oxygen	12	(2)
Lithiation α to nitrogen	14	(1)
Amides	15	(5)
Benzotriazoles and other 5-membered heterocycles	20	(1)
Formamidines	20	(1)
Nitrosoamines	21	(1)
Imines	22	(1)
Isocyanides	23	(1)
Lithiation of trigonal C--H α to nitrogen	23	(1)
N-oxides and amine-boron complexes	23	(1)
Lithiation α to sulfur	24	(2)
Lithiation α to silicon	26	(1)
Lithiation at unfunctionalised allylic positions	26	(2)
Ortholithiation	28	(45)
Introduction: mechanism	28	(6)
Classes of directing group	34	(2)
N+O class	36	(1)
Secondary and tertiary amides	36	(5)
α-Amino alkoxides	41	(2)
Oxazolines	43	(1)
O-Carbamates	44	(1)
Anilides and N-aryl carbamates	45	(1)
S+O class	46	(4)
N class	50	(1)
Aminomethyl groups	50	(1)
Anilines and isocyanides	51	(1)
Imines, nitriles, hydrazones and nitrogen heterocycles	51	(2)
O class	53	(1)
Ethers and alkoxides	53	(3)
Ketones, esters and carboxylates	56	(2)
X class	58	(1)
Ortholithiation of aromatic heterocycles	59	(1)
Electron-deficient heterocycles	59	(11)
Electron-rich heterocycles	70	(1)
Lithiation of metal-arene complexes	71	(1)
Chromium-arene complexes	71	(1)
Ferrocenes	72	(1)
Lateral lithiation	73	(13)
Mechanism and regioselectivity	73	(2)
Classes of directing group	75	(1)
Secondary and tertiary amides	75	(2)
Nitriles	77	(1)
Oxazolines, imidazolines and tetrazoles	77	(1)
Carboxylates	77	(1)
Carboxylic esters	78	(1)
Ketones	78	(1)
Aldehydes protected as α-amino alkoxides	79	(1)
Alcohols and phenols (cresols) and their derivatives	79	(2)
Sulfur-based functional groups	81	(1)
Aniline and aminoalkylbenzene derivatives	82	(1)
Halogens	83	(1)
Lateral lithiation of heterocycles	83	(3)
Remote lithiation, and β-lithiation of non-aromatic compounds	86	(1)
Superbases	87	(3)
Cooperation, competition and regioselectivity	90	(21)
References	96	(15)
Regioselective Synthesis of Organolithiums by X-Li Exchange	111	(38)
Halogen-lithium exchange	111	(25)
Reactivity	111	(7)
Mechanism	118	(6)
Synthesis of aryllithiums	124	(3)
Synthesis of heteroaryllithiums	127	(5)
Synthesis of vinyllithiums	132	(2)
Synthesis of alkyllithiums	134	(1)
Diastereoselective halogen-lithium exchange	135	(1)
Tin-lithium exchange	136	(3)
Chalcogen-lithium exchange	139	(3)
Selenium-lithium exchange	139	(2)
Tellurium-lithium exchange	141	(1)
Sulfur-lithium exchange	141	(1)
Phosphorus-lithium exchange	142	(7)
References	142	(7)
Regioselective Synthesis of Organolithiums by C-X Reduction	149	(20)
Reductive lithiation of alkyl and aryl halides	149	(5)
Reductive lithiation with lithium metal	149	(1)
Reductive lithiation promoted by arenes	150	(4)
Reductive lithiation of C--O bonds	154	(4)
Reductive lithiation of C--N bonds	158	(1)
Reductive lithiation of C--S bonds	159	(6)
Reduction of sulfides	159	(5)
Reduction of sulfones	164	(1)
Reductive lithiation of C--C bonds and π-bonds	165	(4)
References	165	(4)
Stereoselective and Stereospecific Synthesis of Organolithiums	169	(72)
Configurational stability of organolithiums	169	(45)
Determining configurational stability	169	(6)
Unfunctionalised organolithiums	175	(1)
Secondary organolithiums	175	(1)
Primary organolithiums	175	(1)
Solvent effects	176	(1)
Cyclopropyllithiums	176	(2)
Organolithiums α to oxygen	178	(1)
Simple acyclic α-alkoxy organolithiums	178	(2)
Cyclic α-alkoxy organolithiums	180	(3)
Oxiranyllithiums	183	(1)
Allylic and benzylic α-alkoxy organolithiums	184	(2)
Organolithiums α to nitrogen	186	(1)
Cyclic α-amino organolithiums: 3-membered rings	186	(2)
Pyrrolidinyllithiums and piperidinyllithiums: 5- and 6-membered rings	188	(3)
Lithiated formamidines	191	(1)
Acyclic α-amino organolithiums	192	(1)
Benzylic and allylic α-amino organolithiums	193	(2)
Crystallographic and theoretical data	195	(2)
Organolithiums α to halogens	197	(2)
Organolithiums α to sulfur	199	(1)
Lithiated sulfides	199	(3)
Lithiated thiocarbamates	202	(1)
Lithiated sulfones	202	(2)
Mechanism of racemisation	204	(1)
Organolithiums α to selenium	205	(2)
Organolithiums α to phosphorus	207	(1)
Organolithiums α to silicon	207	(1)
Benzyllithiums	208	(1)
Secondary benzyllithiums	208	(3)
Tertiary benzyllithiums	211	(1)
Vinyllithiums	212	(1)
Summary	213	(1)
Stereospecific synthesis of organolithiums by X--Li exchange	214	(10)
Tin-lithium exchange	214	(1)
Vinylstannanes	214	(1)
α-Heterosubstituted stannanes	214	(2)
Non-heterosubstituted stannanes	216	(6)
Halogen-lithium exchange	222	(1)
Selenium-lithium exchange	222	(1)
Sulfur-lithium exchange	223	(1)
Other metal-lithium exchanges	223	(1)
Stereospecific deprotonation	223	(1)
Diastereoselective deprotonation	224	(2)
Diastereoselective lateral lithiation	224	(1)
Diastereoselective ortholithiation	225	(1)
Enantioselective deprotonation	226	(15)
References	235	(6)
Stereospecific and Stereoselective Substitution Reactions of Organolithiums	241	(32)
Stereospecific reactions of organolithium compounds	241	(17)
Introduction	241	(1)
Vinyllithiums	242	(1)
Non-stabilised alkyllithiums	242	(1)
The general rule: retention (SE2ret)	242	(4)
The exception -- alkylation of lithiated N-alkyl pyrrolidines and piperidines: inversion (SE2inv)	246	(1)
Rearrangements ([1,2] and [2,3], except Brook rearrangements) of unstabilised organolithiums: inversion (SE2inv)	247	(2)
Stabilised alkyllithiums: retention (SE2ret) or inversion (SE2inv)?	249	(1)
Benzyllithiums	249	(7)
Allyllithiums	256	(1)
Rearrangements of stabilised organolithiums	257	(1)
Stereoselective substitution in the presence of chiral ligands	258	(15)
Introduction: Mechanisms	258	(1)
Chiral ligands	258	(2)
Enantioselective deprotonation	260	(1)
Enantioselective substitution	260	(1)
Configurational stability, stereospecificity, and dynamic resolutions	261	(1)
Dynamic thermodynamic resolution	262	(6)
Dynamic kinetic resolution	268	(1)
Summary: mechanisms of asymmetric functionalisation with (--)-sparteine	268	(1)
References	269	(4)
Regio- and Stereoselective Addition Reactions of Organolithiums	273	(64)
Intermolecular addition to π bonds: Carbolithiation	273	(9)
Carbolithiation of simple alkenes	273	(1)
Carbolithiation of conjugated alkenes and alkynes	274	(2)
Carbolithiation of functionalised alkenes	276	(4)
Enantioselective carbolithiation	280	(2)
Intramolecular addition and substitution reactions: anionic cyclisation	282	(55)
Anionic cyclisations onto carbonyl compounds and derivatives	282	(1)
Cyclisations of aryllithiums -- Parham cyclisations	282	(2)
Cyclisations of alkenyllithiums	284	(2)
Cyclisations of alkyllithiums	286	(1)
Cyclisations of alkynyllithiums	287	(1)
Anionic cyclisations onto epoxides	288	(2)
Anionic cyclisations onto alkyl halides and similar compounds	290	(3)
Anionic cyclisations onto alkenes and alkynes	293	(1)
Cyclisation onto activated alkenes	293	(1)
Cyclisation onto unactivated alkenes	294	(7)
Cyclopentanes	301	(7)
Cascade reactions	308	(2)
Tetrahydrofurans	310	(2)
Pyrrolidines	312	(2)
Tetrahydrothiophenes	314	(1)
Stereoselectivity and mechanism	314	(7)
Anionic cyclisation onto allenes	321	(1)
Anionic cyclisation onto alkynes	321	(6)
Anionic cyclisation onto aromatic rings	327	(2)
References	329	(8)
Organolithium Rearrangements	337	(28)
Shapiro Reaction	337	(3)
Brook Rearrangements	340	(6)
[1,2-]-Brook Rearrangements	342	(2)
[1,3]-Brook Rearrangements	344	(1)
(1,4]-Brook Rearrangements	345	(1)
[1,4]-Retro-Brook rearrangements	346	(1)
[1,2]-Wittig Rearrangements	346	(5)
Mechanism and scope	346	(2)
Stereospecificity	348	(2)
[1,2]-Wittig rearrangements in synthesis	350	(1)
[2,3]-Wittig Rearrangements	351	(14)
Regioselectivity	352	(2)
Diastereoselectivity	354	(1)
Double bond geometry	354	(1)
Syn/anti relative stereochemistry	355	(1)
Stereospecificity and enantioselectivity	355	(1)
Stereospecific rearrangements of chiral allyl ethers	355	(2)
Stereoselective rearrangements with chiral auxiliaries	357	(1)
Stereospecific rearrangements of chiral organolithiums	357	(2)
[2,3]-Aza-Wittig rearrangements	359	(1)
References	360	(5)
Organolithiums in Synthesis	365	(12)
Ochratoxin: ortholithiation and anionic Fries rearrangement	365	(1)
Corydalic acid methyl ester: lateral lithiation	366	(1)
Fredericamycin A: ortho, lateral and α-lithiation	367	(2)
(±)-Atpenin B: metallation of an aromatic heterocycle	369	(1)
Flurbiprofen: metallation with LiCKOR superbases	370	(1)
California Red Scale Pheromone: α- and reductive lithiation	371	(1)
C1-C9 of the Bryostatins: diastereoselective bromine-lithium exchange	372	(1)
(S)-1-Methyldodecyl acetate, a Drosophila pheromone: (--)-sparteine assisted enantioselective lithiation	373	(1)
(--)-Paroxetine: (--)-sparteine-promoted asymmetric lithiation and substitution	374	(3)
References	375	(2)
Index	377