Reduction of acylsilanes

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... 

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. 

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]. 

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

Acylsilanes are yet another class of valuable synthetic intermediates, and new methods for their synthesis are always welcome. In the first of several examples reported this year, the silyl allene (168) has been used as a common intermediate for the preparation of a diverse range of acylsilanes with a,p-olefinic, a,p-acetylenic, and a-keto substituents. Alkyl-substituted acylsilanes are now available via a high-yielding process in which an acyl-lithium (generated in situ from an alkyl-lithium and CO) is trapped by MeaSiCl. Cyclic acylsilanes have been prepared from cyclic vinylsilanes by way of an epoxidation-reductive ringopening-oxidation sequence. ... 

Two alternative routes to (+)-swainsonine (ent-37S) developed by Chen and Tsai, Hke that used in their synthesis of lentiginosine (c Scheme 47 Section 3.3.2), created the bond to C-8a by means of free radical cycUzations onto an acylsilane. The first approach entailed the creation of the C-l/C-8a bond (Scheme 86). Amide formation between the amine 638 and the acid chloride prepared in situ from the chiral lactone-acid 639 yielded (—)-640, which was cyclized with base to the imide (—)-641 in 91% yield. Chemoselective reduction of the C-2 carbonyl group, acid-catalyzed reaction with thiophenol, and protection of the hydroxyl substituent as the benzoate gave 642 as a mixture of isomers. After hydrolysis of the dithiane to the acylsilane 643 with iodobenzene bis(trifluoroacetate), treatment with tri-butyltin hydride and l,lCazobis(cyclohexane-l-carbonitrile) (ACCN) as radical initiator produced the indohzidin-5-one 644 in 86% yield as a... 

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-... 

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). 

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