Acylsilanes, reduction

The steric bulk of the silyl groups in acylsilanes influences their asymmetric reduction to give chiral secondary alcohols by borane complexed with )-2-amino-3-... 

Cathodic reduction potentials of acylsilanes have been determined by polarography in EfitNI/DMF70 or by cyclic voltammetry in EuNClCU/MeCN using a glassy carbon cathode40 as shown in Table 17. 

TABLE 17. Cathodic reduction potentials of acylsilanes and related compounds40 70... 

Cathodic reduction of acylimidazoles in the presence of chlorotrimethylsilane gives the corresponding acylsilanes in satisfactory yields (equation 93)117. Acylsilanes having a... 

Enantioselective reduction of the prochiral cyclic acylsilane 42 with growing cells of the yeast Kloeckera corticis (ATCC 20109) yielded the optically active reduction product (R)-43 (Scheme 8)53. On a preparative scale, the l-silacyclohexan-2-ol (R)-43 was isolated in 60% yield with an enantiomeric purity of 92% ee. Repeated recrystallization of the biotransformation product from n-hexane raised the enantiomeric purity to 99% ee. 

Scheme 15)62. After terminating the reaction at a conversion of 38% (relative to total amount of substrate rac-78), the product (S)-43 was separated from the nonreacted substrate by column chromatography on silica gel and isolated on a preparative scale in 71% yield (relative to total amount of converted rac-78) with an enantiomeric purity of 95% ee. Recrystallization led to an improvement of the enantiomeric purity by up to >98% ee. The biotransformation product (S)-43 is the antipode of compound (/ )-43 which was obtained by enantioselective microbial reduction of the acylsilane 42 (see Scheme 8)53. The nonreacted substrate (/ )-78 was isolated in 81% yield (relative to total amount of nonconverted rac-78) with an enantiomeric purity of 57% ee. For further enantioselective enzymatic hydrolyses of racemic organosilicon esters, with the carbon atom as the center of chirality, see References 63 and 64. 

Reduction of the imine or oxime of an acylsilane provides an appropriate route to SMA derivatives, as several routes to acylsilanes are now available. This process is... 

If HMPA is used in stoichiometric amount in THF as the solvent, then substitution of the chlorine atom occurs providing the corresponding C-silylated imine, the precursor of the acylsilane pivaloylsilane. This imine can also be regarded as a good precursor of an SMA through its reduction. Reduction of the iminoylchloride into the non-silylated imine is a side reaction. 

Enamines have been prepared through reductive-trimethylsilylation of cyanohydrins as precursors of acylsilanes.la 192 As indicated above, these enamines are also excellent starting materials for synthesizing RSMAs via reduction of the corresponding iminium chlorides with sodium borohydride.la,lb... 

It has already been shown that aliphatic acylsilane enamines serve as precursors for RSMA (See Sections III.B.2.i and III.B.2.j) via reduction of their iminium chloride. Transformation of aromatic acylsilane enamines into the corresponding ASMA does not require a reduction step. Their protonolysis leads directly to ASMA, aromatization occurring during the process, sometimes with migration of a silyl group.180... 

Aliphatic acylsilane imines and their salts are readily accessible (see Sections III.B.21 and III.B.2.j). Their reduction by a chiral boronate provides ready access to the corresponding chiral RSMAs.310... 

S-Substituted a-lithiated silyl enol ether 557 has been prepared by reductive lithia-tion of vinyl tellurides834 and sulfides835,836 with lithium 1 -(dimethylamino)naphthalenide (LDMAN). This intermediate 557 gave, after inverse Brook rearrangement, the enolate 558 and after hydrolysis the corresponding acylsilane (Scheme 151). 

Denmark reported a protocol for the formation of 3-substituted azepines 4 from nitro acylsilanes 3, which were formed by the conjugate addition of an acylsilane-derived dienol-ether 2 to nitroalkenes 1 <07JOC7050>. The reaction of the nitro acylsilane with aluminium-amalgam gave a mixture of azepines and lactams, however, this was overcome by conversion of the acylsilane to an aldehyde prior to the reductive cyclisation. 

In this case, alkene insertion into the h-H bond is likely to occur first, producing a linear alkyl species. CO insertion would produce an acyl species, which would then be followed by reductive elimination of the acylsilane product. Enohzation, followed by rapid reaction of HSiR3 with the OH group, traps out the enol silyl ether. The Hy produced Irom this sUylation step is used to hydrogenate some of the starting alkene. Thus, the maximum yield will generally be only 66% of the enol silyl ether product. The enol silyl ethers can be readily converted into silyl ketones (equation 10). 

All biotransformations mentioned above represent enantioselective reductions. In contrast, the reduction of the cyclic chiral acylsilane vac-225 with growing cells of Kloeckera corticis (ATCC 20109) into a 1 1 mixture of (S,R)-226 and (jR,S)-226 is an example of a diastereoselective conversion (yield of reduction product 95%, diaster-eomeric excess 90% de)19,283. 

Acylsilanes arc reduced to a-alkoxysilancs by a variety of metal hydrides. Reduction with (—)-chlorodiisopinocamphcnylborane provides (R)-alcohols in >80% cc and in 30-65% yield.6... 

Radical cyclization reactions have proven to be a very efficient approach for polycyclic natural product synthesis. In many cases, the last step involves a reduction of a cyclic radical with formation of a new stereogenic center. Very good stereochemical control has been achieved with such polycyclic radicals. For example, Beckwith has reported a highly stereoselective formation of a quinolizidine ring (Scheme 19, Eq. 19.1) [41b]. This process is the key reaction in a four-step synthesis of epilupinine and the stereochemical outcome results from a stereoselective axial reduction by tin hydride of a bicyclic radical. In a related process, Tsai has prepared silylated hydroxyquinolizidine by radical cyclization to an acylsilane followed by a radical-Brook rearrangement (Scheme 19, Eq. 19.2) [42]. 

The common approach to a-silyl alcohols involves acylsilane-based processes such as nucleophilic addition of Grignard reagents, reduction, and retro-Brook rearrangement c, in a-lithio silyl ethers. 

Acylsilanes appear to be extraordinarily susceptible to reductions of this type. 

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