Chiral acylsilanes

Addition to chiral acylsilanes.6 Addition of alkyllithium or Grignard reagents to a-chiral aldehydes shows only modest (about 5 1) syn-selectivity. In contrast, the same reagents add to chiral acylsilanes with high sy -selectivity to give, after... 

Stereoselectivities observed in the reactions of the a-chiral acylsilanes are explained by consideration of the the Felkin-Anh model. The conformers depicted in Figures 9 and 10 are predicted to be those through which nucleophilic addition occurs. The sterically demanding TMS group apparently differentiates between the a-hydrogen (S) and the a-methyl (M) substituents. This preference for the conformation in Figure 9 results in a highly stereoselective reaction. 

Table 10 Selectivities in the Reaction of Nucleophiles with a-Chiral Acylsilanes (36) and Aldehydes (39)...

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. 

Startg. chiral acylsilane treated with 2 eqs. -BuLi in THF at —78° for 5 min intermediate hydroxysilane (Y 92% diastereomer ratio > 100 1), treated with BU4NF in DMF at room temp. 5yn-product. Overall Y 89% (diastereomer ratio > 100 1). The diastereomer ratio is noticeably lower (5 1) by direct reaction from the corresponding aldehyde. F.e. inch reaction with allyltrimethylsilane (in the presence of TiCy and with allylmagnesium bromide s. M. Nakada et al., J. Am. Chem. Soc. 110, 4826-7 (1988) review of synthesis and synthetic potential of acylsilanes s. A. Ricci, A. DeglTnnocenti, Synthesis 1989, 647-60 review of the steric influence of the trimethylsilyl group s. J.R. Hwu, N. Wang, Chem. Rev. 89, 1599-615 (1989). 

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-... 

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. 

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... 

Notably, the asymmetric Claisen rearrangement of ci j-allylic ot-(trimethylsilyl)vinyl ethers with the chiral aluminum reagent produced optically active acylsilanes with the same absolute configuration as those from trans-allylic a-(trimethylsilyl)vinyl ethers (eq 5). ... 

There have been only a limited number of developments in this area, the majority of which involve the use of lithium diisopropylamide (LDA) with chiral l,3-dioxolan-4-ones to deprotonate the C-5 position and allow reaction with a suitable electrophile (Equation 21). Electrophiles used to alkylate the enolate include iodomethane <1996HCA1696>, ethyl crotonate <1998SL102>, a,/ -unsaturated ketones <2006T9174>, various substituted nitrostyrenes <2004T165>, substituted nitroaryl fluorides <2003SL2325> and acylsilanes <2002TA1825>. 

Acylsilanes can be reduced with the borane-oxazaborolidine system to give the corresponding silicon-containng chiral alcohols with good to excellent enanti-oselectivity [98]. 

Catalysts constituting a C2-symmetric 1,2-diamine have been used to hydrogenate a-aryl aldehydes to yield chiral alcohols, under dynamic kinetic resolution conditions. Hydrogenation of the carbonyl group of acylsilanes with 3 (presence of f-AmOK or NaBHr as activator) is apphcable to acquisition of a-silyl aUylc alcohols from conjugated acylsilanes. ... 

Acylsilanes undergo highly diastcrcoselectivc reactions with RLi and RMgX to afford rvn-adducts, particularly when the chiral center is substituted by a phenyl group.5... 

The stereoselectivity of the reaction of 1 -alkynylzinc bromides 130 (R == heptyl or Ph) with various chiral a-benzyloxy aldehydes 131 (R = Me, /-Pr or PhCH20CH2) to yield the alcohols 132 depends on the nature of the substituents R and R Regiospecific propargylation with acylsilanes is exemplified by the reaction of the organozinc bromide 133 (from 2-octynyl bromide and zinc dust in THF) with benzoyltrimethylsilane, followed by desilylation, to yield only the alcohol 134 . 

Scheme 6.19 Enantioselective cyanation/Brook rearrangement/C-acylation of acylsilanes catalyzed hy chiral metal alkoxides.

Johnson s group developed a catalytic asymmetric cyanation/1,2-Brook rearrangement/C-acylation of acylsilanes with cyanoformates (Scheme 19.14). In the presence of (i ,/ )-(salen)Al 19, the corresponding cyanohydrin trimethylsilyl ethers of a-keto esters were obtained in moderate to good enantioselectivities (61-82% enantiomeric excess). Access to chiral (silyloxy)nitrile anions is facilitated by metal cyanide-promoted Brook rearrangement reaction of acylsilanes. 

The steric bulk of the silyl groups in acylsilanes influences their asymmetric reduction to give chiral secondary alcohols by borane complexed with (5)-(-)-2-amino-3-methyl-l,l-diphenylbutan-l-ol . The enantiomeric excess increases from 50% to 94% by replacement of the PhMe2Si group with the PhsSi group. 

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... 

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