Silyl enol esters

Silyl enolates react with acyl cation equivalents to give the C- and/or O-acylated products (Equation (90)).333 Fluoride-catalyzed reaction using acyl fluorides is valuable for O-acylation of silyl enolates derived from aldehydes and ketones.334 CuCl also promotes the 0-acylation with acyl chlorides.335 The CuCl-promoted reaction of ester silyl enolates results in exclusive (7-acylation. Combined use of BiCfl and Znl2 (or Nal) effects catalytic (7-acylation of ketone silyl enolates with acyl chlorides. 

Lewis acid-catalyzed tandem Michael imino-aldol reactions enable the one-pot synthesis of 7-acyl-(5-lactams from a, j6-unsaturated thio-esters, silyl enolates and imines [15]. For the initial Michael addition, the combination of SbClj with Sn(OTf>3 (5 mol %) proved to be efficient. However, after the addition of the imino compound the iminoaldol product was isolated in moderate yield. For the enhancement of turnover and yield, Sc(OTf)3, once again proved to be the Lewis acid of choice (Scheme 4, 15 16 = 81 19, 94%). 

Mukaiyama Aldol Condensation. As expected, the chiral titanium complex is also effective for a variety of carbon-carbon bond forming processes such as the aldol and the Diels-Alder reactions. The aldol process constitutes one of the most fundamental bond constructions in organic synthesis. Therefore the development of chiral catalysts that promote asymmetic aldol reactions in a highly stereocontrolled and truly catalytic fashion has attracted much attention, for which the silyl enol ethers of ketones or esters have been used as a storable enolate component (Mukaiyama aldol condensation). The BINOL-derived titanium complex BINOL-TiCl2 can be used as an efficient catalyst for the Mukaiyama-ty pe aldol reaction of not only ketone si ly 1 enol ethers but also ester silyl enol ethers with control of absolute and relative stereochemistry (eq 11). ... 

Several synthetic methods employ the 3-halo indolenine intermediates generated by halogenations as intermediates. Danishefsky and coworkers found that the chlor-oindolenine from the methyl ester of W, W -dibenzyltryptophan can be converted to 2-substituted products using a variety of nucleophiles, including allylic boranes and staimanes, enamines and ester silyl enol ethers [68]. 

In a total synthesis of ( )-widdrol (151), Danishefsky and Tsuzuki have set up the necessary stereochemical detail by using a variation of Irelands allylic ester silyl enolate rearrangement [i.e. (149) -> (150)]. 

The stereochemistry of the ester silyl enol ether Claisen rearrangement can be controlled not only by the stereochemistry of the double bond in the allylic alcohol, but also by the stereochemistry of the silyl enol ether. The chair transition state predicts that the configuration at the newly formed C—C bond will be determined by the E- or Z-configuration of the silyl enol ether. 

Unlike the chiral, neutral N-F reagents, the [N-F] ammonium salts of cinchona alkaloids are employed for the fluorination of a number of substrates ketone and ester enolates, (3-keto esters, a-cyano esters, a-nitro esters, a-amino esters, silyl enol ethers, enol acetates, nitrile anions, and... 

Difunctional target molecules are generally easily disconnected in a re/ro-Michael type transform. As an example we have chosen a simple symmetrical molecule, namely 4-(4-methoxyphenyl)-2,6-heptanedione. Only p-anisaldehyde and two acetone equivalents are needed as starting materials. The antithesis scheme given helow is self-explanatory. The aldol condensation product must be synthesized first and then be reacted under controlled conditions with a second enolate (e.g. a silyl enolate plus TiCl4 or a lithium enolate), enamine (M. Pfau, 1979), or best with acetoacetic ester anion as acetone equivalents. 

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

This effect is the basis of the synthetic importance of ester enolate Claisen rearrangements in which enolates or silyl enol ethers of allylic esters are rearranged into 4-pentenoate esters. 

The (acyloxy)borane complex 9, readily available from tartaric acid derivative 8, also catalyzes aldol additions of silyl enol ethers34 and silylketene acetals3 5 in an enantioselective manner. Thus,. u -ketones 10 and /Thydroxy esters 12 are available34, as well as a-unsubstituted ketones 1135. 

As an alternative to lithium enolates. silyl enolates or ketene acetals may be used in a complementary route to pentanedioates. The reaction requires Lewis acid catalysis, for example aluminum trifluoromethanesulfonate (modest diastereoselectivity with unsaturated esters)72 74 antimony(V) chloride/tin(II) trifluoromethanesulfonate (predominant formation of anti-adducts with the more reactive a,/5-unsaturated thioesters)75 montmorillonite clay (modest to good yields but poor diastereoselectivity with unsaturated esters)76 or high pressure77. 

Enolizable compounds can be used for Meerwein reactions provided that the keto-enol equilibrium is not too far on the side of the ketone for example, P-dicar-bonyl compounds such as acetylacetone are suitable (Citterio and Ferrario, 1983). The arylation of enol esters or ethers (10.12) affords a convenient route for arylating aldehydes and ketones at the a-carbon atom (Scheme 10-48). Silyl enol ethers [10.12, R = Si(CH3)3] can be used instead of enol ethers (Sakakura et al., 1985). The reaction is carried out in pyridine. 

Silyl enol ethers and ketene acetals derived from ketones, aldehydes, esters and lactones are converted into the corresponding o/i-unsaturated derivatives on treatment with allyl carbonates in high yields in the catalytic presence of the palladium-bis(diphenylphosphino)ethane complex (32). A phosphinc-free catalyst gives higher selectivity in certain cases, such as those involving ketene acetals. Nitrile solvents, such as acetonitrile, are essential for success. 

Ketones and carboxylic esters can be a hydroxylated by treatment of their enolate forms (prepared by adding the ketone or ester to LDA) with a molybdenum peroxide reagent (MoOs-pyridine-HMPA) in THF-hexane at -70°C. The enolate forms of amides and estersand the enamine derivatives of ketones can similarly be converted to their a hydroxy derivatives by reaction with molecular oxygen. The M0O5 method can also be applied to certain nitriles. Ketones have also been Qc hydroxylated by treating the corresponding silyl enol ethers with /n-chloroperoxy-... 

Okazoe, T. Takai, K. Oshima, K. Utimoto, K. J. Org. Chem., 1987, 52, 4410. This procedure is also successful for silyl esters, to give silyl enol ethers Takai, K. Kataoka, Y. Okazoe, T Utimoto, K. Tetrahedron Lett, 1988, 29, 1065. 

Addition of silyl enol ethers or silyl ketene acetals to unsaturated ketones or esters... 

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