Silyl diastereoselective addition

This isomerization was used in the heteroconjugate addition to the acyclic system. Therefore, the substituted olefin 72, in which the double bond is conjugated with both sulfone and silicon atoms, undergoes a diastereoselective addition of CHsLi. The resulting lithium alcoholate is quantitatively converted into the silyl ether dianion 73 and the addition of deuterium oxide afforded the functionalized product 74 in excellent yield (equation 16. 

Scheme 1.19. Diastereoselective addition of a Danishefsky diene derivative (216) to (V,o- The product distribution is indicative of a stepwise reaction, because the major diastereoisomer (( )-217) obtained after hydrolysis of the silyl enol ether function of the primary adduct cannot result from a concerted [4 + 2] cycloaddition.

In a separate, elegant use of 165, Rychnovsky and coworkers have carried out a diastereoselective addition of methyl acetate-derived silyl ketene acetal to aldehyde 174 to afford adduct 175 in high diastereomeric purity (Scheme 15) [102]. Hydroxy ester 175 was subsequently employed as an intermediate in the total synthesis of the polyene macrolide antibiotic Roflamycoin. This work highlights a novel application of the chiral catalyst system in reagent-controlled coupling of chiral functionahzed substrates which by themselves display only mod-... 

Diastereoselective Additions of Chiral Silyl Ketene Acetals to Imines... 

Diastereoselective addition of chiral (E)-crotylsilanes to RCHO tetrahydrofurans.1 BFj etherate is the most efficient Lewis acid promotor for diastereoselective addition of a-substituted /3-silyl-(E)-crotylsilancs (1) to a- and /3-benzyloxy aldehydes to form... 

Highly diastereoselective addition of silyl enol ethers and silyl ketene acetals to aryl aldimines complexed with tricarbonylchromium in the presence of 5 mol% Sc(OTf)3 gave -amino ketones and P-amino esters in good to excellent yields [108]. 

Highly diastereoselective addition of a chiral ketene silyl acetal (70) to nitrones (71) to give products (72) has been reported (Scheme 7). The stereochemistry has been rationalized in terms of si-face approach by nitrone (73) and by the open transition state (74). ... 

Products 4 and 9 have adjacent stereogenic centers. Hisashi Yamamoto of the University of Chicago has introduced J. Am. Chem. Soc. 2007,129,2762) the linchpin reagent acetaldehyde super silyl enol ether 11. Diastereoselective addition of 11 to the enantiomerically-pure aldehyde 10, with concomitant silyl transfer, followed by the addition of allyl magnesium bromide delivered the protected triol 12 in high de and ee. 

An interesting example of a diastereoselective addition of a phosphorus nucleophile to imines is the reaction used for the preparation of iminosugar phosphonates (Scheme 47.23). In this synthetic protocol, imine 101 reacted with a silylated P(III) derivative with high diastereoselectivity, producing intermediate 102 that upon deprotection was... 

Helmchen [67] and Oppolzer [68] investigated and documented the use of camphor-derived auxiliaries in Mukaiyama aldol reactions. Silyl ketene acetals 106 and 108 participate in diastereoselective additions to aldehydes in the presence of TiCl4, affording adducts with up to 99 1 diastereoselectivity (Equations 7 and 8). 

The first catalytic enantioselective Mannich reaction was documented by Kobayashi, using the conveniently assembled BINOL-derived Zr catalyst 212 (Scheme 11.32) [150]. This catalyst was highly effective in enantioselective additions of silyl ketene acetals to N-(o-hydroxyphenyl)-aldimines such as 210. In a further expansion of the reaction scope, ( )- and (Z)-substituted a-alkoxy silyl enol ethers were observed to undergo diastereoselective additions to aldimines, giving syn and anti amino alcohols, respectively [151]. These processes were utilized in the rapid assembly of (2R,3S)-3-phenyliso-serine (214), a precursor of the C,3 side chain of paclitaxel, known to be essential for its anticancer activity. 

Carreira has reported that N-acylated camphorsultams such as 85 undergo stereoselective cycloaddition with TMSCHN2 (Scheme 18.18) [81-83]. Treatment of the initial cycloadduct 86 with acid provided the corresponding A -pyrazoline 87 (dr=90 10) [81]. In general, the isolated pyrazolines serve as versatile synthetic intermediates for further elaboration. In the depicted example, N-acetylation and subsequent diastereoselective addition of the silyl ketene acetal 88 furnish methyl ester 89 as a single diastereomer [82]. 

The synthetic problem is now reduced to cyclopentanone 16. This substance possesses two stereocenters, one of which is quaternary, and its constitution permits a productive retrosynthetic maneuver. Retrosynthetic disassembly of 16 by cleavage of the indicated bond furnishes compounds 17 and 18 as potential precursors. In the synthetic direction, a diastereoselective alkylation of the thermodynamic (more substituted) enolate derived from 18 with alkyl iodide 17 could afford intermediate 16. While trimethylsilyl enol ether 18 could arise through silylation of the enolate oxygen produced by a Michael addition of a divinyl cuprate reagent to 2-methylcyclopentenone (19), iodide 17 can be traced to the simple and readily available building blocks 7 and 20. The application of this basic plan to a synthesis of racemic estrone [( >1] is described below. 

In addition to the boron trifluoride-diethyl ether complex, chlorotrimcthylsilanc also shows a rate accelerating effect on cuprate addition reactions this effect emerges only if tetrahydrofuran is used as the reaction solvent. No significant difference in rate and diastereoselectivity is observed in diethyl ether as reaction solvent when addition of the cuprate, prepared from butyllithium and copper(I) bromide-dimethylsulfide complex, is performed in the presence or absence of chlorotrimethylsilane17. If, however, the reaction is performed in tetrahydrofuran, the reaction rate is accelerated in the presence of chlorotrimethylsilane and the diastereofacial selectivity increases to a ratio of 88 12 17. In contrast to the reaction in diethyl ether, the O-silylated product is predominantly formed in tetrahydrofuran. The alcohol product is only formed to a low extent and showed a diastereomeric ratio of 55 45, which is similar to the result obtained in the absence of chlorotrimethylsilane. This discrepancy indicates that the selective pathway leading to the O-silylated product is totally different and several times faster than the unselective pathway" which leads to the unsilylated alcohol adduct. A slight further increase in the Cram selectivity was achieved when 18-crown-6 was used in order to increase the steric bulk of the reagent. 

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