Acylsilanes with nucleophiles

SYNTHETIC REACTIONS USING BROOK REARRANGEMENTS IN THE REACTIONS OF ACYLSILANES WITH NUCLEOPHILES... 

Reaction of Acylsilanes with Nucleophiles, Either of Which Contains an a-Leaving Group... 

Aryl(trimethylsiloxy)carbenes. Acylsilanes (153) undergo a photoinduced C —> O silyl shift leading to aryl(trimethylsiloxy)carbenes (154).73,74 The carbenes 154 can be captured by alcohols to form acetals (157) 73 or by pyridine to give transient ylides (Scheme 29).75 LFP of 153 in TFE produced transient absorptions of the carbocations 155 which were characterized by their reactions with nucleophiles.76 The cations 155 are more reactive than ArPhCH+, but only by factors < 10. Comparison of 154 and 155 with Ar(RO)C and Ar(RO)CH+, respectively, would be of interest. Although LFP was applied to generate methoxy(phenyl)carbene and to monitor its reaction with alcohols,77 no attempt was made to detect the analogous carbocation. 

Recently, acylsilanes have been utilized as useful intermediates in organic synthesis [57], For example, treatment of acylsilanes with the fluoride ion generates the corresponding acyl anions which react with electrophiles. On the other hand, by using the electrochemical method, acylsilanes serve as acyl cation equivalents because nucleophiles are introduced at the carbonyl carbon. Chemical oxidation of acylsilanes with hydrogen peroxide which affords the corresponding carboxylic acids has been reported [58], However, the anodic oxidation provides a versatile method for the introduction of various nucleophiles... 

The reaction of acylsilanes with appropriate carbon nucleophiles, followed by the Brook rearrangement, provides a novel source of carbanions which can be further elaborated on treatment with a reactive electrophile, allowing the formation of two carbon-carbon bonds in a one-pot reaction. 

Reactions of acylsilanes with a nucleophile (Scheme 6.4. Eq. 1) are among the most common and versatile methods for generation of an a-silyl alkoxide because various combinations of the two components for facilitating Brook rearrangement are possible. 

The equilibrium between a-silyl alkoxides and silojq carbanions can be shifted toward the carbanion side by introduction of a conjugating group into either or both the acylsilane and the nucleophile. In 1980, Reich et al. reported that treatment of all l-substituted acylsilanes with vinyllithium followed by a variety of electrophiles affords a-substituted enol silyl ethers 22 via a siloxy allyllithium intermediate 21 fScheme 8.1Similar reactions using phenyllithium give products in which electrophilic quenching occurred at the benzylic position. 

Scheme 3-147. Nucleophile-catalyzed reactions of acylsilanes with carbonyl...

Three different routes to the key compounds for the sila-Peterson elimination, the a-alkoxydisilanes 157, are described in the literature, namely A, reaction of silyllithium reagents with ketones or aldehydes B, addition of carbon nucleophiles to acylsilanes C, deprotonation of the polysilylcarbinols. In addition, method D, which already starts with the reaction of 2-siloxysilenes with organometallic reagents, leads to the same products. The silenes of the Apeloig-Ishikawa-Oehme type synthesized so far are summarized in Table 4. 

The dilithio derivative of 1,4-bisphenylsufonylbutane 61 was formed prior to the introduction of homochiral acylsilane 56 into the reaction mixture. The nucleophilic carbonyl addition/Brook rearrangement/elimination sequence delivered bis (fi)-vinyl silyl ether 64 in high yield and with very high selectivity through the putative intermediates 62 and 63. This short and effective synthesis of 55, this time made as the major isomer, was then completed as described above for 54. 

Because of the readiness with which cyclopropanes are formed from 3-halopropyl ketones, cyclization of the latter to dihydrofurans is difficult, and few examples of such cyclizations have been reported (Scheme9.18). Acylsilanes, on the other hand, are more nucleophilic at oxygen than ketones, and readily undergo intramolecular O-alkylations [73-75],... 

A third possibility of chemical modification is conversion into an acylsilane which reduces the oxidation potential of the corresponding ketone by approximately 1 V. A peak potential of 1.45 V (relative to Ag/AgCl) for the oxidation of undecanoyltrimethylsilane has been reported. Preparative electrochemical oxidations of acylsilanes proceed in methanol to give the corresponding methyl esters. A two-step oxidation process must be assumed because of the reaction stoichiometry —oxidation of the acylsilane results in the carbonyl radical cation which is meso-lytically cleaved to give the silyl cation and the acyl radical, which is subsequently oxidized to give the acyl cation as ultimate electrophile which reacts with the solvent. A variety of other nucleophiles have been used and a series of carboxylic acid derivatives are available via this pathway (Scheme 49) [198]. 

Catalytic multicomponent synthesis of highly substituted pyrroles has been described. A one-pot reaction uses DBU with the commercially available thiazolium salt 513 to produce the necessary nucleophilic zwitterionic catalyst in situ, which promotes a conjugate addition of acylsilanes (sila-Stetter) and unsaturated ketones to generate 1,4-dicarbonyl compounds in situ. Subsequent addition of various amines promotes a Paal-Knorr reaction, affording the desired polysubstituted pyrrole compounds in a one-pot process in moderate to high yields (Scheme 129) <2004OL2465>. Microwave heating dramatically reduced the reaction time (from 16 h to 30 min), but offered no improvement in yields. 

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

Although l,n-Brook rearrangements other than the 1,2-shift have been becoming increasingly important from a synthetic point of view, the main focus in this chapter will be on the 1,2-C-to-0 silyl shift because it uniquely enables a carbonyl carbon atom in acylsilanes 5 to act as a 1,1-dipole (electrophilic/nucleophilic character) 6 in combination with a nucleophile (Scheme 62). 

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. 

The nucleophilic and electron-accepting properties of heterocyclic nucleophilic carbenes 36 were also used in combination with the electrophilic/nucleophilic character of acylsilanes via Brook rearrangement, leading to the invention of a sila-Stetter reaction by Scheidt and coworkers fScheme 6.24). The iminium structure in 37, generated by addition of the carbene catalyst 36 to the acylsilanes, promotes a Brook rearrangement to afford enol silyl ether 38. The alcohol additive present in the reaction causes desilylation to produce nucleophilic enaminol 39, which adds to a,p-unsaturated ketones to give 40. The formation of aryl ketone expels the carbene catalyst and produces 1,4-diketone 41. 

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