Lithio sulfides

These results indicate that the a-lithio sulfides are not configurationally stable at —78 C and thus, the high diastereoselectivity reflects the thermodynamic preference of 35 A over 35B3). 

Early efforts to synthesize optically active epoxides using chiral a-lithio sulfoxide anions or chiral complexes of a-lithio sulfides have been reviewed. These approaches usually yield epoxides of low optical purity. More successful, if indirect, approaches are outlined in Section 3.2.2.7. 

A) and used in organic synthesis. a-Lithio sulfides give useful carbanion reactions and sulfur ylids can be formed (secs. 8.6, 8.8.B). The difficulties in preparing primary and secondary amines by traditional methods (from halides or tosylates via reaction with imides or azides, sec. 2.7) make the hydroboration-amination sequence a mild and useful alternative for the synthesis of amines. 

Carbon-sulfur bonds can be formed by the reaction of elemental sulfur with a lithio derivative, as illustrated by the preparation of thiophene-2-thiol (201) (700S(50)104). If dialkyl or diaryl disulfides are used as reagents to introduce sulfur, then alkyl or aryl sulfides are formed sulfinic acids are available by reaction of lithium derivatives with sulfur dioxide. 

This technique is especially useful for the preparation of a-lithio ethers, sulfides, and silanes.36 The lithium radical anions of naphthalene, 4, 4/-di-f-butyldiphenyl (DTBB) or dimethylaminonaphthalene (LDMAN) are used as the reducing agent. 

Reaction of l,3-bis(methylthio)-2-methoxypropane with 2 moles of lithium diisopropylamide5 (or w-butyllithium) effects (a) the elimination of methanol to form l,3-bis(methylthio)propene and (b) the lithiation of this propene to generate l,3-bis(methylthio)allyllithium in solution. Its conjugate acid, l,3-bis(methylthio)propene, can be regenerated by protonation with methanol, and has also been prepared (a) in 31% yield by reaction of methylthioacetaldehyde with the lithio derivative of diethyl methylthiomethylphosphonate,5 (b) in low yield by acid-catalyzed pyrolysis of l,l-bis(methylthio)-3-methoxypropane,6 and (c) in low yield by acid-catalyzed coupling of vinyl chloride with chloromethyl methyl sulfide.7... 

It is reasonable to suppose that the anti-lithio compound 4a is the precursor of 5a (reaction occurs with retention of configuration). That 4a is formed, not under kinetic but under thermodynamic control, is shown by the reaction of the diastereomeric a-stannylated sulfides 3a and 3b, giving the same diastereomeric ratio as 5. 

For 1,4 addition to enones, the cuprates of the bislactim ethers have been found to be very useful [88AG(E)1194]. These are made by reacting the lithio derivatives with CuBr SMe2 in the presence of dimethyl sulfide. 

Conversion of Sulfides to Organolithium Compounds Lithio-de-phenylthio-substitution... 

Methyl- or 2-ethyl-benzo[Z> ]thiophenes are conveniently prepared by treatment of 2-benzo[6]thienyllithium with the appropriate alkyl sulfate <70AHC(11)177). Clemmensen or Wolff-Kishner reductions of the 2-acylbenzo[Z>]thiophenes are useful, but since acylation produces a mixture of the 2- and 3-acyl isomers (Section 3.14.2.4), these must be separated. Cyclization of phenyl phenacyl sulfide with hydrofluoric acid leads exclusively to 2-phenyl-benzo[6]thiophene, and 3-phenylbenzo[6]thiophene can be rearranged to the 2-isomer in hydrofluoric acid (Section 3.15.2.3.2). Aromatization of 2-cycIohexenylbenzo[6]thiophene, obtained by condensation of the 2-lithio reagent with cyclohexanone, gives 2-phenyl-benzo[6]thiophene, and the reaction is adaptable to the 2-(l-naphthyl) derivative also. 

Bromine-lithium exchange applied to the sulfide obtained from the reaction between 2-fluorobenzonitrile and 2-bromothiophenol promotes an intramolecular attack on the nitrile function. Hydrolysis of the resulting tricyclic lithio-imine produces thioxanthone (Scheme 209). Alternatively, the imine can be trapped with electrophiles... 

By oxidising the sulfide to a sulfone, the synthetic versatility of this class of compounds is further increased. Deprotonation of either or both diastereoisomers of 98 leads, under thermodynamic control, to the equatorial organolithium 101 in which a destabilising interaction between the oxygen lone pair and the lithio substituent is avoided. However, lithium-naphthalene reduction of 102 to the organolithium 103 is axially selective because of the stabilisation afforded to the intermediate radical by the axial lone pair. Protonation of the product gives 104.88... 

The simplest compound in this series, 1-phenylthio- 1-trimethylsilyl ethylene 45, was conveniently prepared by Magnus and co-workers either by reaction of a-lithio vinyl phenyl sulfide 46 with trimethylsilylchloride,53 or by addition of arylsulfenyl-chloride to vinyl trimethylsilane followed by elimination of hydrogen chloride54... 

Allenyl sulfides have been converted into their a-lithio derivatives by deprotonation with n-BuLi in THF at —78 °C1092 or in the presence of TMEDA1093,1094. For example, compound 775 reacted with isobutylene oxide to give compound 776, after cyclization (Scheme 201). This dihydropyran 776 was transformed into atlantone 777, as a mixture of Z/E diastereomers, by treatment with HgCl2 in wet acetonitrile1092. 

Should added unsaturation be desired, the condensation of a 2-cyclopentenone with lithio cyclopropylphenyl sulfide makes possible the formation of an ally lie alcohol which can be dehydrated quantitatively (Scheme 11). Thermal rearrangement, followed by mercuric ion-promoted hydrolysis of the vinylsulfide part structure completes the synthetic transformation. 

---