A-Thio carbanions

The pioneering work on thia-[2,3]-Wittig rearrangement was reported by Rautenstrauch in 1971 °. The reaction of allyl sulfides 137 with n-BuLi at —30°C for 1.5-4 h gave homoallyl sulfide or thiol 138 ([2,3]-product) exclusively (equation 81). In contrast, a similar reaction of vinyl sulfide 139 gave no [1,2]-rearrangement product 141 albeit a-thio-carbanion was generated as shown by its methylation to 140 (equation 82) °. 

The most popular method for generation of a-thio-carbanion (migration terminus) is direct lithiation (deprotonation) with alkyllithium or lithium amide. These deprotonation methods are widely applicable to various substrates, not only benzyl or allyl sulfides , but also dithioacetals 142 which form 143 (equation 83), and a phosphonate substituted system 144 which gives 145 (equation 84). ... 

Taking an example of a sulfur-stabilized benzyllithium compound, Hoffmann and coworkers performed two reactions of the racemic a-thio carbanion with a racemic or a chiral aldehyde [Eq. (3)] [17-19], and found that both reactions afford an identical diastereomeric ratio of the product. From these results, they have concluded that the sulfur-stabilized benzyllithium compound epimerizes faster than it reacts with the aldehyde, i.e., it is configurationally labile in THF at -78°C. 

On the other hand, the a-thio carbanion of butyl phenyl sulfide was estimated to be stable in 2-methyl-THF at -120°C [17,18].The a-selenobenzyllithium [19] and the lithiated phosphine oxide [20, 21] are labile in THF at -78°C (Fig. 7), whereas the a-selenobutyllithinm and the a-sulfonylbenzyUithiiun are stable in Et20/THF at-105 C [22] and in THF at-78°C, respectively [19].Thea-silylben-zyllithium is configurationally labile at 0°C in THF [19], the a-bromopentyllith-iiun being stable in Trapp-solvent at -110°C [17]. 

Hoppe and coworkers showed that the lithiated (S)-l-phenylethyl thiocar-bamate (Fig. 10a) and the lithiated (S)-cyclohex-2-enyl thiocarbamate (Fig. 10b) are configurationally stable in THF at 0°C and at -70°C, respectively [32,33]. They assumed that this is so because these resonance-stabiUzed tertiary carbanions have pronounced tendency to form solvent-separated ion pairs in THF. A silyl substituent makes the a-thio carbanion configurationally more stable than the parent thiocarbamate without the trimethylsilyl group (Fig. 10c) [34]. 

Most a-thio carbanions are configmationally labile and racemize rapidly even at low temperature as shown in the preceding section. This may be the reason why the asymmetric reaction of a-lithiated thiocarbamates reported by Hoppe and coworkers does not show such high enantioselectivity [34] as attained in the reaction of similar dipole-stabilized a-oxy organolithium compounds [Eq. (4)] [2, 39]. Note that the stereochemistry of the products obtained from a-lithiated thiocarbamates is different from that obtained in the a-lithiated carbamate [Eq.(5)]. 

Inversion of configuration in the above reaction is in contrast to retention of stereochemistry generally observed in the enantioselective reaction with carbonyl compounds. There are a few reports on the Sg2 reaction with a carbonyl compound proceeding with inversion [32,44]. Recently, Hoppe and coworkers have observed that the configurationally stable chiral a-thio carbanion derived from chiral thiocarbamates reacted with carbonyl compounds to create the quaternary center with complete inversion of the carbanionic center [Eq. (8)] [32], whereas the reaction of the corresponding a-oxy carbanion with electrophiles (including carbonyl compounds) proceeds with retention of configuration [45]. 

The Sg2 reaction on the 5p -like hybridized carbanion tends to proceed with inversion of the stereochemistry [45]. It is reasonable that a-thio carbanions, having higher s character than a-oxy carbanions, more frequently invert the stereochemistry on the anionic carbon in the reaction with electrophiles. As in the case of a-lithiated benzyl 2-pyridyl sulfide, the reaction of a-lithiated benzyl 2-quinolyl sulfide also proceeds through a dynamic thermodynamic resolution pathway. The quinolyl group is an excellent protecting group of thiols [46] and can be removed to yield the corresponding chiral thiols without racemization (Tables) [47]. 

Carbanions a to the sulfonyl group can be easily prepared due to their high acidity in comparison with a-Aio carbanions. Although a-sulfonyl carbanions have a more sp -hybridized character than a-thio carbanions [24,56], a-sulfonyl carbanions have been shown by Gais and coworker to have a somewhat higher inversion barrier to racemization than a-thio carbanions [35]. For example, when an enantiomerically pure trifluoromethyl sulfone was first deprotonated with n-BuLi and subsequently protonated with trifluoroacetic acid, the sulfone was recovered with 90% ee [Eq. (12)]. 

Raubenheimer HG, Kruger GJ, Lombard AA, Linford L, Vdjoen JC. Sulfar-containing metal complexes. 12. Reactions of a-thio carbanions with carbene complexes of the type [M(CO)5 0(alkyl)Ar ] and with the carbyne [(f -MeC5H4)-Mn(CO)2(CPh)][BCl4]. Organometallics. 1985 4 275-284. 

A recent paper [44] shows that the treatment of silyl thioketones 68 with lithium diethylphosphite proceeds via a thiophiUc attack followed by a thio-phosphate mercaptophosphonate (69 70) carbanionic rearrangement and the migration of the silyl group from the carbon to the sulfur atom leading to the S-silylated sulfanylphosphonate carbanion 71. The last step represents the first example of the thia-Brook rearrangement (Scheme 18). 

The synthetic utility of a-phosphorus- and a-thio-stabilized carbanions is the subject of numerous reviews.21 Notable are additions of phosphonium ylides (237),183 sulfonium ylides (238),l84 ° oxosulfo-nium ylides (239)184 " and sulfoximine ylides (240)184,1 to electron-deficient alkenes which afford nucleophilic cyclopropanation products. In contrast, with a-(phenylthio)-stabilized carbanions, which are not acyl anion equivalents, either nucleophilic cyclopropanation or retention of the hetero substituent occurs, depending on the acceptor and reaction conditions used. For example, carbanion (241) adds to 1,1-... 

Surprisingly, for jp -hybridized carbanionic centers the reverse order of stabilization is found. The seleno moiety is now more stabilizing than a thio moiety (Scheme 7, cf. Scheme 3). ... 

REACTIONS OF a-THIO- AND a-SELENO-ALKYLLITHIUMS BEARING HYDROGENAND/OR HYDROCARBON SIDE CHAINS ON THEIR CARBANIONIC CENTER... 

This chapter is devoted exclusively to the alkylation of the above mentioned organometallic reagents with alkyl halides, epoxides and oxetanes. It includes a large variety of organosulfur- and organoselen-ium-stabilized carbanions derived from saturated and unsaturated sulfides, selenides, sulfoxides, selen-oxides and sulfones as well as those carbanions bearing another heteroatomic moiety. The chapter excludes, however, those organometallics which can be viewed as a-thio and a-seleno enolates. 

The nucleophilicity of sulfur and its ability to stabilize a-carbanions provide sulfur compounds with unique opportunities for sigmatropic processes consecutive rearrangements are no exception. The formation of salt (140) via Sn2 alkylation of ( )-2-butenyl bromide (139) followed by deprotonation leads to the intermediate allyl vinyl ether (141) which, under the conditions of the deprotonation, undergoes a thio-Claisen rearrangement to afford thioamide (143 Scheme 10). Thermolysis of (143) at elevated temperature affords the Cope product (142) in addition to some of its deconjugated isomer. Several unique characteristics of the thio-Claisen sequence should be noted first, the heteroatom-allyl bond is made in the alkylation step, this connection teing not notrtudly practised in the parent Claisen reaction ... 

An a-sulfonyl carbanion (and other stabilized carbanions, e.g., phosphorus ylides) can add to a thio-substituted triple bond to furnish 5-membered ring products. The corresponding alkoxy compound behaves similarly. 

This test showed that a-amino- [7] and a-oxy- [8] alkyllithium compounds except for their benzyl- or allyllithium compounds are configurationally highly stable, and a-thio-[9], a-selenoalkyllithium compounds [10], and lithiated phosphine oxides [11] are labile. Thus, this test proves that lithium carbanions are either configurationally stable or labile and affords reliable evidence to de-... 

Fig. 7. Configurational stability of a-thio-, a-seleno-, a-phosphono-, a-sulfonyl, a-silyl and a-bromo carbanions estimated by the Hoffinaim test...

Interestingly, the stereochemical outcome in the reaction of a-Hthiated benzyl phenyl sulfide is different from that in the reaction of a-hthiated benzyl methyl ether which proceeds through a dynamic thermodynamic resolution pathway [Eq. (7)] [15,43]. Taking account of Wiberg s results, namely, that the a-oxy carbanion of dimethyl ether places the lone pair of carbanion syn to the methyl group by the electron repulsive effect [25], the difference in the stereochemical outcome between a-thio and a-oxy carbanions would be ascribed to their different preferred conformations. A similar change in the stereochemical outcome has been observed in reactions of dipole-stabilized a-thio and a-oxy organoUth-ium compound, as shown in Eqs. (4) and (5). 

A new thiophen synthesis is based on deprotonation and cyclization of the resultant carbanion (65) of a keten dimethylthioacetal. Other applications of cr-(phenylthio)- or cr-(alkylthio)-alkyl-lithiums include preparations of disparlure (the sex pheromone of the gypsy moth) and other chiral epoxides,of an anti-peptic-ulcer diterpene from Croton sublyratus, of carbene-thiometal chelates through reaction with fCr(CO)gl or fW(CO)jl, of olefins via )ff-hydroxy-sulphides, and of Michael adducts of enones. In other work, the chiral solvent l,4-dimethylamino-2,3-dimethoxybutane is employed in enantioselective addition reactions of cr-thio-carbanions with ketones and Michael acceptors. a,P -Elimination of cr-thio-carbanions such as (66) provides a useful synthesis of olefins, and a 2-(lithiomethylthio)-A -oxazoline (67) has been used to prepare a C-labelled thiiran for a microwave study of the valence tautomerism of allene episulphide. ... 

Carbanions stabilized by phosphorus and acyl substituents have also been frequently used in sophisticated cyclization reactions under mild reaction conditions. Perhaps the most spectacular case is the formation of an ylide from the >S-lactam given below using polymeric Hflnig base (diisopropylaminomethylated polystyrene) for removal of protons. The phosphorus ylide in hot toluene then underwent an intramolecular Wlttig reaction with an acetyl-thio group to yield the extremely acid-sensitive penicillin analogue (a penem I. Ernest, 1979). 

The pA of 1,3-dithiane is 36.5 (Cs" ion pair in THF). The value for 2-phenyl-1,3-dithiane is 30.5. There are several factors which can contribute to the anion-stabilizing effect of sulfur substituents. Bond dipole effects contribute but carmot be the dominant factor because oxygen substituents do not have a comparable stabilizing effect. Polarizability of sulfur can also stabilize the carbanion. Delocalization can be described as involving 3d orbitals on sulfur or hyperconjugation with the a orbital of the C—S bond. MO calculations favor the latter interpretation. An experimental study of the rates of deprotonation of phenylthionitromethane indicates that sulfur polarizability is a major factor. Whatever the structural basis is, there is no question that thio substituents enhance... 

Freparatively useful induced diastereoselectivities have been reported mainly for 1,1-di-substituted allyllithium derivatives which bear carbanion-stabilizing substituents. l-[Methyl-thio-l-(trimethylsilyl)-2-propenyl]lithium106 and the appropriate 1-phenylthio107 derivative, generated from the allylic sulfide with sec-butyllithium, in the reaction with tetrahydropyranyl-protected pregnolone, furnish a single diastereomer. 

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