Silyl ketene acetyl

Schemes 28 and 29 illustrate Curran s synthesis of ( )-hirsutene [( )-1]. Luche reduction58 of 2-methylcyclopentenone (137), followed by acetylation of the resulting allylic alcohol, furnishes allylic acetate 138. Although only one allylic acetate stereoisomer is illustrated in Scheme 28, compound 138 is, of course, produced in racemic form. By way of the powerful Ireland ester enolate Clai-sen rearrangement,59 compound 138 can be transformed to y,S-unsaturated tm-butyldimethylsilyl ester 140 via the silyl ketene acetal intermediate 139. In 140, the silyl ester function and the methyl-substituted ring double bond occupy neighboring regions of space, a circumstance that favors a phenylselenolactonization reac-...

Three years after the discovery of the asymmetric BINOL phosphate-catalyzed Mannich reactions of silyl ketene acetals or acetyl acetone, the Gong group extended these transformations to the use of simple ketones as nucleophiles (Scheme 25) [44], Aldehydes 40 reacted with aniline (66) and ketones 67 or 68 in the presence of chiral phosphoric acids (R)-3c, (/ )-14b, or (/ )-14c (0.5-5 mol%, R = Ph, 4-Cl-CgH ) to give P-amino carbonyl compounds 69 or 70 in good yields (42 to >99%), flnfi-diastereoselectivities (3 1-49 1), and enantioselectivities (72-98% ee). 

Fu has also explored intermolecular C-acetylation of silyl ketene acetals by AC2O for the formation of quaternary stereocenters catalyzed by planar chiral fer-... 

Scheme 8.21 Fu s planar chiral ferrocenyl PPY-catalyzed C-acetylation of silyl ketene acetals [60, 64].

Z-j0-keto ester 58, but proved to be unsuccessful. When 58 was treated with 2 eq. of LDA no desired product was obtained. When the silyl ketene acetal of 58 was formed and heated under reflux, only a very small amount of 56 and 57 was obtained. This mixture, when subjected to ozonolysis and acetylation, gave a 1.5 1 mixture of 52 and 54. 

Analogously, esters can be C-acetylated by conversion into the corresponding silyl ketene acetal followed by treatment with AcCl. Depending on the coupling conditions (neat AcCl or AcCl/EtsN ), either the ds -/3-siloxycrotonate ester or the corresponding /l,y-isomer is produced (eqs and ). The third possible isomer (trawy-zS-siloxycrotonate) is accessible either by sily-lation of the acetoacetic ester (TMSCl, EtsN, THE, or by HgBr2/Et3SiBr-catalyzed equilibration of the cis isomer. ... 

The silyl ketene acetal strategy can also be used to effect y-acetylation of a,/3-unsaturated esters (AcCl/cat. ZnBra, CH2CI2, rt) " and /3-ketoesters (AcCl, Et20, -78°C).i"... 

TMAL) reaction sequence for the synthesis of P-lactones. Despite the relatively high diastereoselectivity, the ZnCb mediated aldol reaction was only optimized when smaller silyl and thiol groups of the ketene acetyl were employed for the improved efficiency of the subsequent lactonization. The methodology was utilized in the synthesis of (-)-panicilin D, a pancreatic lipase inhibitor, where the ketene thioacetal 60 was added to aldehyde 59, upon which lactonization followed by deprotection yielded the 3-lactone 61 as a diastereomeric mixture (9.3 1) in modest yield. 

As outlined in the previous paragraph, chiral Brpnsted base organocatalysts appear to be most effective when equipped with an additional Brpnsted acidic moiety, for example, hydrogen bond donors like (thio)urea. Apparently, both functionalities catalyze the asymmetric Mannich reaction in a cooperative fashion, that is, simultaneous activation of both the nucleophile and the electrophile. However, activation of the electrophile can also be accomplished with a single, enantiomerically pure Brpnsted acid. In this respect, readily available chiral phosphoric acids are most commonly applied [88-90]. In 2004, the groups of Akiyama and Terada independently from each other reported the first asymmetric Mannich reaction of silyl ketene acetals or acetyl acetone with imines utilizing chiral phosphoric acid catalysts, which... 

The scope of the Brpnsted acid-catalyzed asymmetric Mannich reaction was later extended by Gong and colleagues, which used instead of silyl ketene acetals or acetyl acetone simple ketones as nucleophiles [95]. The combination of various cycloketones, phenylamines, and aldehydes in the presence of the chiral phosphoric acid catalyst 134 or 135, respectively, afforded the corresponding anti-Mamich products in high yields with good enantioselectivities (75-98% ee)... 

Activation of C-X Bonds. Even more important than carbonyl activation, ZnBr promotes substitution reactions with suitably active organic halides with a variety of nucleophiles. Alkylation of silyl enol ethers and silyl ketene acetals using benzyl and allyl halides proceeds smoothly (eq 13). Especially useful electrophiles are a-thio halides which afford products that may be desulfurized or oxidatively eliminated to result in a,p-unsaturated ketones, esters, and lactones (eq 14). Other electrophiles that have been used with these alkenic nucleophiles include Chloromethyl Methyl Ether, HC(OMe)3, and Acetyl Chloride... 

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]. 

Chiral ft-hydroxy esters The N-acetyl derivative 1 of Oppolzer s auxiliary can be converted into the 0-silyl-N,0-ketene acetal 2, which reacts with aldehydes in the presence of TiCU to afford aldols 3 or 4. These arc hydrolyzed to /3-hydroxy esters 5. The stereoselectivity depends upon the stcric demands of the aldehyde group R mainly, with... 

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