Asymmetric Synthesis

1 Chirality.- 1.1 The phenomenon of chirality.- 1.2 The biological significance of chirality: the need for asymmetric synthesis.- 1.3 The selective synthesis of enantiomers.- 1.4 The enantiomeric purity of natural products.- 1.5 The stereogenic unit and types of chiral compound.- 1.6 Centrally chiral compounds of carbon and silicon.- 1.7 Centrally chiral compounds of nitrogen and phosphorus.- 1.8 Centrally chiral compounds of sulphur.- 1.9 Axially chiral compounds.- 1.10 Chiral molecules with more than one stereogenic unit: diastereomers.- 1.11 The selective synthesis of diastereomers.- 1.12 Prochirality: enantotopic and diastereotopic groups.- 1.13 Absolute configuration 20 Reference and notes.- 2 The description of stereochemistry.- 2.1 Compounds with one stereogenic centre.- 2.2 Axially chiral compounds.- 2.3 Compounds with more than one stereogenic unit.- 2.4 The topicity of enantioselective reactions.- 2.5 The relative topicity of diastereoselective reactions.- 2.6 Further points on correct terminology.- References and notes.- 3 Analytical methods: determination of enantiomeric purity.- 3.1 Polarimetric methods.- 3.2 Gas chromatography methods.- 3.3 Liquid Chromatographic methods.- 3.4 NMR spectroscopy.- 3.4.1 Chiral derivatising agents (CDAs).- 3.4.2 Chiral solvating agents (CSAs).- 3.4.3 Chiral lanthanide shift reagents (CLSRs).- 3.5 Concluding remarks.- References and notes.- 4 Sources and strategies for the formation of chiral compounds.- 4.1 Chiral starting materials.- 4.1.1 Amino acids and amino alcohols.- 4.1.2 Hydroxy acids.- 4.1.3 Alkaloids and other amines.- 4.1.4 Terpenes.- 4.1.5 Carbohydrates.- 4.2 Methods for the formation of chiral compounds.- 4.2.1 Use of naturally occurring chiral compounds as building blocks.- 4.2.2 Resolution.- 4.2.3 Methods of asymmetric synthesis.- 4.2.4 Special methods.- 4.3 Mechanistic considerations.- References and notes.- 5 First- and second-generation methods: chiral starting materials and auxiliaries.- 5.1 Non-stereodifferentiating methods.- 5.1.1 Classical resolution ((lR)-cis -permethric acid).- 5.1.2 Resolution using a chiral auxiliary.- 5.1.3 Sulphoximines.- 5.1.4 Methods using enantiomerically pure building blocks.- 5.2 First-generation methods.- 5.2.1 Sugars.- 5.2.2 Amino acids.- 5.2.3 Terpenoids.- 5.2.4 Hydroxy acids.- 5.3 Second-generation methods: nucleophiles bearing a chiral auxiliary.- 5.3.1 General principles.- 5.3.2 Chiral enolate and aza-enolate equivalents.- 5.3.3 Asymmetric aldol reactions.- 5.3.4 Asymmetric ?-amino anions.- 5.3.5 Chiral sulphoxides.- 5.4 Electrophiles bearing chiral auxiliaries.- 5.4.1 Asymmetric Michael additions.- 5.4.2 Chiral acetals.- 5.4.3 Asymmetric additions to carbonyl compounds.- 5.5 Chiral auxiliaries in concerted reactions.- 5.5.1 Diels-Alder cycloaddition.- 5.5.2 The Claisen-Cope rearrangement.- References.- 6 Third- and fourth-generation methods: asymmetric reagents and catalysts.- 6.1 C—C bond-forming reactions.- 6.1.1 Asymmetric alkylation.- 6.1.2 Asymmetric Michael reaction.- 6.1.3 Asymmetric nucleophilic additions to carbonyl compounds.- 6.1.4 Asymmetric [2 + 2] cycloadditions.- 6.1.5 Asymmetric Diels-Alder reaction.- 6.1.6 Crotylboranes.- 6.1.7 Asymmetric formation of alkene double bonds.- 6.2 Chiral acids and bases.- 6.3 Asymmetric oxidation methods.- 6.3.1 Asymmetric epoxidation of alkenes.- 6.3.2 Asymmetric oxidation of sulphides.- 6.3.3 Asymmetric dihydroxylation.- 6.3.4 Chiral oxaziridines and their uses.- 6.4 Asymmetric reduction, double bond isomerisation and hydroboration.- 6.4.1 Catalytic hydrogenation with chiral transition metal complexes.- 6.4.2 Asymmetric double bond isomerisation.- 6.4.3 Asymmetric hydroboration of alkenes.- 6.4.4 Asymmetric reduction using chiral boranes and borohydrides.- 6.4.5 Chirally modified LiAlH4.- 6.5 Enzymatic and microbial methods.- 6.5.1 Enzymatic reduction.- 6.5.2 Enantioselective microbial oxidations.- 6.5.3 Esterases and lipases.- References.- 7 Asymmetric total synthesis.- 7.1 First-generation methods.- 7.1.1 (R)-(+)-Frontalin.- 7.1.2 (-)-Prostaglandin E1.- 7.1.3 The Merck synthesis of (+)-thienamycin.- 7.2 Second-generation methods.- 7.2.1 Prelog-Djerassi lactone.- 7.2.2 (R)-Muscone.- 7.2.3 (-)-Podophyllotoxin.- 7.2.4 (-)-Steganone.- 7.2.5 (+)-?-Allokainic acid.- 7.2.6 Leiobunum defence secretion.- 7.3 Third-generation methods.- 7.3.1 Carbocyclic iododeoxyuridine.- 7.4 Fourth-generation methods.- 7.4.1 A tricyclic analogue of indacrinone.- 7.4.2 (S)-(-)-Propranolol.- 7.4.3 Takasago (-)-menthol synthesis.- 7.4.4 (-)-Prostaglandin E1.- 7.4.5 Compactin and mevinolin analogues.- References.