Acylsilanes with lithium enolates

Scheme 3-62. [3 + 4] cycloaddition reaction of flf,/0-unsaturated acylsilanes with lithium enolates of a,y0-unsaturated ketones. 

Scheme 3-153. Sequential reactions of acylsilanes with lithium enolates and...

Murai and coworkers reported on operationally simple aldol reactions with lithium enolates generated from carbonylation of silylmethyl lithium species [57]. Upon 1,2-silicon shift, a-silyl acyllithium species can be stereo-selectively converted to (E) lithium enolates that undergo addition to aldehydes to give /3-hydroxy acylsilanes (Scheme 14). 

Anionic 1,2-silyl migrations from C to O were applied to the [3 + 2] annulations of /J-X-substituted a,/J-unsaturated acylsilanes (X=SPh and SiMe3) 153 with lithium enolates 154,... 

The addition of carbonyl compounds towards lithiated 1-siloxy-substituted allenes does not proceed in the manner described above for alkoxyallenes. Tius and co-work-ers found that treatment of 1-siloxy-substituted allene 67 with tert-butyllithium and subsequent addition of aldehydes or ketones led to the formation of ,/i-unsaturated acyl silanes 70 (Scheme 8.19) [66]. This simple and convenient method starts with the usual lithiation of allene 67 at C-l but is followed by a migration of the silyl group from oxygen to C-l, thus forming the lithium enolate 69, which finally adds to the carbonyl species. Transmetalation of the lithiated intermediate 69 to the corresponding zinc enolate provided better access to acylsilanes derived from enolizable aldehydes. For reactions of 69 with ketones, transmetalation to a magnesium species seems to afford optimal results. 

Even the starting acylsilane 39 can be easily prepared via a Brook isomerization by the reaction of silylmethyllithium 41 with carbon monoxide " °. Initially, the reaction gives the corresponding unstable acyllithium 42 which underwent the Brook isomerization affording the stable lithium enolate (equation 16). 

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). 

Acylsilanes. Carbonylation of trimethylsilylmethyllithium (1) in ether at 15° followed by quenching with ClSilCH,), results in the trimethylsilyl enolate (2) of acetotri-methylsilane. The reaction evidently involves insertion of CO to give an acyllithium (a), which undergoes a 1,2-silicon shift to give the lithium enolate (b) of an acylsilane. 

The McCoy method also allows the preparation of cyclopropylacylsilanes 33. Treatment of a-haloacylsilanes with lithium diisopropylamide (LDA) or with lithium tetramethylpiperidide (LUMP) affords enolates which combine with a variety of electrophilic olefins to produce cyclopropane derivatives33. The major diastereomers formed in the reactions of 2-chloro-l-(/er/-butyldimethylsilyl)ethanone are usually the civ-compounds, while the corresponding a-bromo acylsilane exhibits a higher degree of trans selectivity. 

Enol silyl ethers of acylsilanes. On treatment with butyllithium and trimethyl-silyl chloride, these compounds undergo enol silylation, tellurium-lithium exchange, and O — C silyl migration. The lithium enolates are further silylated. 

Reich et al. also reported a similar elimination strategy that involves a combination of acylsilanes bearing an a-leaving group and an alkyllithium. Thus, reaction of a-phenylthioacylsilane 17, derived from the corresponding lithium enolate, with a variety of nucleophiles proceeded smoothly at lower temperatures to give an enol silyl ether 18 in a stereochemically defined manner tScheme 6.121. 

When lithium enolates derived from amides react with acylsilanes, the resulting /ff-lithioamides or homoenolates are stabilized by intramolecular coordination of a amide carbonyl group and react with electrophiles such as allyl bromide and imines to give y hydroxy yff-substituted amides (Scheme 3-153). 

Transition metal-catalyzed silicon-based cross-coupling reaction has emerged as a versatile carbon-carbon bond-forming process with high stereocontrol and excellent functional group tolerance [35], For example, (a-benzoyloxy)alkenylsilanes 105, prepared as a pure -isomer by 0-acylation of a lithium enolate derived from the corresponding acylsilane, reacts with carboxylic acid anhydrides in the presence of [RhCl(CO)2]2, giving rise to a-acyloxy ketones 106, which are then converted into 1,2-diketones by acidic workup (Scheme 5.27) [36]. 

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>. 

The synthetic use of acylsilanes depends to a large extent on the ease of migration of Si to an alternative site in the molecule after addition of a suitable nucleophile. For instance, enolate anions add to the carbonyl carbon atom of a-chloroacyltrimethylsilanes, the McsSi unit migrating to the a-C atom with displacement of Cl. In this case, the product can be desilylated to give a /8-diketone. Alternatively, the Si can migrate to the carbonyl O atom, as in Scheme 14, where either a homoenolate ion is set up for further alkylation or, in the case of 2-furyl-lithium addition, the furyl ring opens to give a cumulated dienolate system. 

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