Carbanions a to

The big difference between the extent of asymmetric induction on the addition to a prostereogenic carbonyl group of simple carbanions a to a chiral sulfoxide on the one hand and enolates of sulfinyl esters on the other, can be attributed to the capacity of the ester function to chelate magnesium in the transition states and intermediates. The results already described for the addition of chiral thioacetal monosulfoxide to aldehydes (see Section 1.3.6.5.) underscore the importance of other functions, e.g., sulfide, for the extent of asymmetric induction. 

Normally, reactive derivatives of sulfonic acids serve to transfer electrophilic sulfonyl groups259. The most frequently applied compounds of this type are sulfonyl halides, though they show an ambiguous reaction behavior (cf. Section III.B). This ambiguity is additionally enhanced by the structure of sulfonyl halides and by the reaction conditions in the course of electrophilic sulfonyl transfers. On the one hand, sulfonyl halides can displace halides by an addition-elimination mechanism on the other hand, as a consequence of the possibility of the formation of a carbanion a to the sulfonyl halide function, sulfenes can arise after halide elimination and show electrophilic as well as dipolarophilic properties. 

Formation of /3 C—C bonds is also known, but generally requires the generation of a carbanion a to sulfur and its interaction with a carbonyl centre. Dieckmann cyclization of (136) readily affords ethyl 3-oxo-3,4,5,6-tetrahydro-2F/-thiin-2-carboxylate, while the presence of a sulfone group renders a methyl substituent sufficiently acidic to react as in equation (75) (78JCS(Pl)l32l). Sulfur alone is apparently not sufficiently activating for this method to be useful for the preparation of unfunctionalized molecules. 

Many examples of the nucleophilic attack of organometallic compounds at the sulfur atom of thiocarbonyl groups were reported in the 1970s by Beak, Vialle, Ohno, Schaumann and their co-workers [119, 120, 327-329]. This thiophilic addition opens the way for a new method of preparation of carbanions a to sulfur. 

The stabilized carbanion a to a sulfonyl group has been used mainly for carbon-carbon bond-forming purposes by reactions with electrophiles [109, 110, 386]. Their importance is based on the efficiency of their preparation, of their use particularly for alkylation procedures and on the elaboration of reliable methods for sulfonyl group elimination. One example is shown here, with a synthesis of fl//-trans-squalene [396] close to the Biellman synthesis (see Section 4.2.1.4). 

Base is used in a second step to generate a carbanion a to the sulfonyl group. 

The stability of carbanions a to silicon facilitates nucleophilic attack on vinylsilanes (see p. 78). 

The most utilized Umpolung strategy is based on formyl and acyl anion equivalents derived from 2-lithio-l,3-dithiane species. These are readily generated from 1,3-dithianes (thioacetals) because the hydrogens at C(2) are relatively acidic (p f 31). In this connection it should be noted that thiols (EtSH, pi 11) are stronger acids compared to alcohols (EtOH, 16). Also, the lower ionization potential and the greater polarizability of the valence electrons of sulfur compared to oxygen make the divalent sulfur compounds more nucleophilic in Sj,2 reactions. The polarizability factor may also be responsible for the stabilization of carbanions a to sulfur. ... 

Typical examples of the reactions of carbanions a to dithiane are shown in Scheme 2. 

Finally, zearalenone was obtained by intramolecular alkylation of the carbanion a to the benzylic sulfide, which occurs readily with potassium hexamethyldisilazane. After cyclization, the double bond was created by oxidation of sulfide to sulfoxide followed by pyrolytic elimination, a technique described in more detail in the next section (Scheme 12). 

Other applications of carbanions a to a sulfone in total syntheses have recently been reported. Most of them used allylic sulfones or allylic halides. Two examples are reported here. In the synthesis of a precursor of cembranolides, a sulfone derived from geranyl bromide was coupled with an allylic alcohol epoxide (Scheme 65). An interesting point was that the coupling reaction gave high yields only when the lithiated sulfone was allowed to react with the epoxymagnesio alkoxide (the lithium salt of the epoxy alcohol did not react at all with the lithiated sulfone). 

The second mechanistic paper involved the reactivity of carbanions a to pentaco-ordinated phosphorus in spirooxyphosphoranes." In particular, the reaction of 39 with benzaldehyde at — 78 °C was studied in detail. The products were 40 and a mixture of E and Z alkenes (41 a,b). The preliminary mechanistic results suggested that the E,Z selectivity was determined by a combination of kinetic and thermodynamic control. 

Carbanions a to silicon are stabilized by the overlap of the filled 2p orbital on carbon with the vacant antibonding orbital of carbon-silicon bond ((a -p)K conjugation) (Scheme 1 A). For example, the a-carbanions of allylsilanes or similar compounds are easily generated by base removal of a proton (eq (9)) [6]. 

Ester-based chiral auxiliaries have also beat used in other settings. P-Alk-oxyesters 1.27 of (R)-1 -phenylethanol 1.1 (R = Me, Ar = Ph) or (5)-1-naphthyl-ethanol 1.1 (R = Me, Ar = 1-Np) are transformed into dural synthons by reactions with a lithiated carbanion a to phosphorous followed by hydrogenolysis [194], Ethers 1.28 of chiral alcohols 1.1 undergo selective alkylations or hydroxyalkyla-tions [169]. The auxiliaries can be removed by hydrogenolysis. Enol or dienol ethers 1.29 and 1 JO suffer [2+2] [195, 196] or [4+2] cycloadditions [49, 197,198, 199], The best stereoselectivities are obtained when the chiral auxiliary is 1.1 (R = r-Pr, Ar=Ph), 1.4 (R=Ph), 1.5 (R = Ph), 1.10 or 1.13. These auxiliaries are cleaved either by acid treatment [199] or by other means in subsequent steps. Acetylene ethers G OC=CR derived from 1.5 (R=Ph) [199a] can undergo stereoselective Pauson-Khand reactions [200, 201], The auxiliaries are removed by treatment of the products with Sml2 in THF-MeOH. 

Several heterocyclic rings promote the formation of lithium carbanions a- to their heteroatoms. These carbanions can be stabilized by dipolar interactions [982], and pyramidalization of the anionic carbon center may sometimes occur [400],... 

In 1992, Ito et al. reported the possibility of replacing THF by tetrahydropyran (THP) in some reactions induced by Sml2 [19,20]. These authors wanted to prepare carbanions a to an amino nitrogen, through the strategy depicted in Scheme 1. The reactions were performed in the mixture THP/HMPA, since the... 

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