Elimination hemithioacetals

Elimination of thiamin diphosphate ylide from the hemithioacetal intermediate yields acetyl dihydrolipoamide. .. 

Step 4 of Figure 29.11 Elimination of Thiamin Diphosphate The product of the HETPP reaction with lipoamide is a hemithioacetal, which eliminates thiamin diphosphate vlide. This elimination is the reverse of the ketone addition in step 1 and generates acetyl dihydrolipoamide. 

Racemization of some substrates can take place through reversible formation of the substrate via an addition/elimination process. The racemization can be acid or base catalyzed. In this section we vill discuss DKR of cyanohydrins and hemithioacetals. 

As in the case discussed above, hemithioacetals can be racemized by elimination/ addition of a small molecule (a thiol in this case) under weak acidic conditions. Rayner et al. reported the first example of DKR of this kind of substrates yielding homochiral a-acetoxysulfides (Figure 4.24) [49]. 

To direct a solvolytic ring opening, 2-methoxycyclopropyllithium (6) was developed as a chain extension conjunctive reagent. The failure of P-elimination to occur in 6 presumably derives from the high strain of cyclopropene and poor orbital overlap for elimination. The aldehyde adducts smoothly solvolyze to give p,Y unsaturated aldehydes (Eq. 22) 23) which are best initially isolated as their hemithioacetals. 

Addition of hydrogen sulfide and thiols is qualitatively similar to reaction with alcohols in that there are two stages, formation of hemithioacetal (or hemithio-ketal) followed by acid-catalyzed elimination of the hydroxy group and substitution of a second —SR (Equations 8.47 and 8.48). The transformation has been studied less extensively than hydration and acetal formation, and relatively little information on mechanism is available. The initial addition appears to be specific base-catalyzed, an observation that implies that RS is the species that adds. The situation is thus similar to cyanide addition. General acid catalysis has, however, been found at pH 1 to 2 for addition of weakly acidic alkyl thiols, and the reaction rate as a function of pH has a minimum and rises both on the... 

When the hemiaminals A (Figure 7.15, Nu = NR3R4) are formed in a neutral or weakly basic solution, they also have the possibility to react further by an SN1 reaction albeit in a different manner than just described for the corresponding hemiacetals (Nu = OR3) and hemithioacetals (Nu = SR3) The OH group of hemiaminals A is then ejected without prior protonation (i.e., simply as an OH ion). This is possible because an especially well-stabilized carbocation is produced at the same time, that is, the iminium ion C (Nu = NR3R4). It finally reacts with the second equivalent of the N nucleophile. The excess proton is eliminated whereupon the V,lV-acetal B (Nu = NR3R4) has been formed. 

Connective Pummerer reactions are transformations where the thionium ion is generated by the addition of a thiol 158 to an aldehyde 157, generating a hemithioacetal 159, which undergoes elimination, yielding the corresponding thionium ion 160. This ion can be trapped by a nucleophile as already described tScheme 20.30). The nucleophile can be introduced by an inter- or intramolecular process, thereby increasing the applicability of this methodology. 

Racemization via a reversible addition/elimination process under mild conditions can be used, with for example cyanohydrins, hemiacetals, hemiaminals and hemithioacetals. SiUca-supported benzyltrimethylammonium hydroxide (BTAH) was used to racemize cyanohydrins and effected an efficient DKR process in tandem with porous ceramic-immobilized lipase (lipase PS-C II) (Scheme 4.22) [57]. 

Hemithioacetals are configurationally unstable due to the elimination-addition of thiols (Scheme 5.33) [8d]. However, irreversible acetylation of hemithioacetals can be achieved using a lipase-catalysed vinyl acetate DKR process to afford essentially a single enantiomeric product in up to 85% yield. Furthermore, the DKR efficiency is increased in the presence of silica gel, which enhances the rate of racemization. 

---