Silylketenes, synthesis

A matched pair combination of the above silylketene acetal and (/ ,if)-2,4-dimethyl-2-heptenal has been applied in a stereoselective synthesis of the C17-C25 fragment of zincophor-... 

D. A. Evans, P. H. Carter, E M. Carreira, J. A. Pmnet, A. B. Charette, M. Lautens Asymmetric Synthesis of Bryosta-tin 2 , Angew. Chem, Int. Ed. Engl. 1998,37,2354-2359. For methodological studies on asymmetric Cu-catalyzed aldol addition, see D. A. Evans, J. Murry, M. C. Koz-lowski C2-Symmetric Cu(II) Complexes as Chiral Lewis Adds. Catalytic Enantiosdective Aldol Additions of Silylketene Acetals to (Benzyloxy)acetaldehyde , J. Am Chem. Soc 1996,118,5814-5815. 

The reaction of Cjq with silylated nucleophiles [47] requires compounds such as silyl ketene acetals, silylketene thioacetals or silyl enol ethers. It proceeds smoothly and in good yields in the presence of fluoride ions (KF/18-crown-6) (Scheme 3.10). The advantage of the latter synthesis is the realization of the cyclopropanation under nearly neutral conditions, which complements the basic conditions that are mandatory for Bingel reactions. Reaction with similar silyl ketene acetals under photochemical conditions and without the use of F does not lead to methanofullerenes but to dihydrofullerene acetate [48]. 

This variation was used for an enantioselective synthesis of anti-a-methyl-p-hydroxy esters using the silylketene acetal derived from (1R, 2S)-N-methylephed-rine-O-propionate (equation II).12... 

Glycosylamines were shown efficient stereodifferentiating templates in the synthesis of enantiomerically pure P-amino acids. They react with silylketene acetals and zinc(II) chloride as the promoting Lewis acid via a Mannich-type pathway to give P-amino acid esters 12 in high yields and high diastereoselectivity [26], (Scheme 9). 

In total synthesis of the structurally unique natural product calcimycin (15), Grieco and others used Ireland-Claisen rearrangement of the ester 17 to synthesize the key intermediate (18)7 (Scheme 1.3g). Monosilylation of the diol 16 followed by treatment with propionyl chloride in pyridine gave rise to the ester 17 in 90% yield. Treatment of 17 with LDA in THF at —78 C, subsequent addition of ferf-butyldimethylsilyl chloride in HMPA, and brief heating of the resulting silylketene acetal provided the corresponding silyl ester. Subsequent hydrolysis of the silyl ester and esterification with diazomethane gave 18 in 90% yield from 17. 

The synthesis of y-lactones from acetals derived from a tartaric acid dithioester was recently reported552. Quenching the readily obtained lithium dienolate (analyzed as its bis-silylketen acetal, Scheme 111, bottom structure) with a series of aldehydes gave only one diastereomeric lactone, generally in ca 60% yield, along with a variable amount of oxidized diester depending on steric factors (Scheme 111). An intramolecular complexa-tion of the lithium atom is assumed to favor the C2-symmetric Z,Z non-planar chelated... 

Danishefsky and coworkers have demonstrated the conversion of lactones to carbocycles by the 3,3-sigmatropic shift of silylketene acetals. Jq the total synthesis of the Fusarium toxin equisetin, for example, keto lactone (138) was converted to its bissilyl derivative (139) by reaction with 2 equiv. of LDA and an excess of TMS-Cl. In situ thermolysis of ketene acetal (1 ) led to a very smooth transformation into ester (140), which was carried on to equisetin (Scheme 26). This methodology was also applied by Schreiber and Smith in the preparation of the cyclohexyl moiety of the immunosuppressive agent FK-506. Ireland-Claisen rearrangement of silylketene acetal (142), prepared by treatment with TBDMS-OTf and triethylamine at low temperature, provided, after hydrolysis of the silyl ester, the carboxylic acid (143) in 71% overall yield (Scheme 27). The strict translation of configuration via a boatlike transition state is typical for this permutation. 

In the enantioselective total synthesis of p-lactone enzyme inhibitor (-)-ebelactone A and B, I. Paterson and coworkers constructed seven stereocenters and a trisubstituted alkene plus a very sensitive p-lactone ring. The backbone of their strategy applied an aldol reaction / Ireland-Claisen rearrangement sequence and used minimal functional group manipulation. The Ireland-Claisen rearrangement was performed in the presence of an unprotected ketone moiety and set a precedent for this protocol. The diastereoselectivity was 96 4, indicating highly ( )-selective silylketene acetal formation. 

Lipstatin is a natural product that exhibits potent inhibitor activity of the pancreatic lipase, and therefore it is a potential lead for the development of antiobesity agents. P.J. Kocienski developed a synthesis for this compound that incorporates an aldehyde-ketene cycloaddition as the key step. The reaction between the aldehyde and silylketene derivative was carried out in the presence of EtAICIs that served as the Lewis acid activator. This transformation led to the formation of four diastereomers in 91% yield, but after desilylation, the desired stereoisomer could be isolated in 64% yield from the mixture. 

Marsden, S. P., Pang, W.-K. Efficient, general synthesis of silylketenes via an unusual rhodium mediated Wolff rearrangement. Chem. Common. 1999, 1199-1200. 

A comprehensive review article on 3-lactam formation via the ester enolate-imine condensation has been written by Hart and Ha. Achiwa and coworkers have published a full paper detailing their work on the synthesis of N-benzyloxy-3-lactams utilizing the reaction of N-benzyloxyimines with silylketene acetals in the presence of TMS-OTf, or with lithium ester enolates. ... 

The reaction has proved to be of synthetic value in the synthesis of silylketenes. ... 

The intramolecular cyclization route to a specific P-lactam often depends on the availability of a P-aminoester having the required stereochemistry. A review which considers the asymmetric synthesis of p-aminoesters is available (94MI475). Ytterbium promoted addition of benzylamine to 2-alkenoic esters having a stereogenic centre at the y-position (94CL827) and triphenyl borate mediated reaction of chiral imines with silylketene acetals have been utilised to give P-aminoesters stereoselectively (93BMC2337). 

The aziridination and amidation reactions of imidoiodanes can be efficiently catalyzed by Rh(II) complexes [810-815]. Dirhodium(II) tetrakis[Al-tetrafluorophthaloyl-(S)-tcrt-leucinate], Rh2(S-TFPTTL)4, has been found to be an exceptionally efficient catalyst for enantioselective aminations of silyl enol ethers 661 with imidoiodane 662 to afford a-amido ketones 663 in high yields and with enantioselectivities of up to 95% ee (Scheme 3.265). The effectiveness of this catalytic protocol has been demonstrated by an asymmetric formal synthesis of (-)-metazocine [810]. This catalyst has also been used for the asymmetric synthesis of phenylglycine derivatives by enantioselective amidation of silylketene acetals with PhINTs [811]. 

Wolff rearrangement has also been applied for the synthesis of silylketenes 25 from silyl diazoketones 24. The ketenes 25 upon further reaction with BnNH2 afforded the corresponding a-silyl benzylamides 26 in good yields. 

H- 2] Cycloaddition is one of the most convenient methods for the construction of optically active four-membered carbon- or heterocyclic rings that are useful intermediates in organic synthesis. Titanium Lewis acids have been found to promote formal [2 + 2] cycloaddition between two olefins with different electronic features [181]. The analogous hetero [2 + 2] addition of a chiral aldehyde to a silylketene can be catalyzed by TiCU to give the propiolactone with high diastereoselectivity as shown in Scheme 14.80. The silyl group in the product can be easily removed by treatment with KF [182]. 

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