Ketene reaction with aldehyde

TABLE 3-4. Reaction of Silyl Ketene Acetals with Aldehydes... 

Ketene dithioketals,1 The reagent undergoes Wittig-Horner reactions with aldehydes or ketones to give 2-alkylidene-l,3-dithianes in 80-100% yield. The corresponding P=S analog reacts with aldehydes in only moderate yield (25-65% yield). 

This topological rule readily explained the reaction product 211 (>90% stereoselectivity) of open-chain nitroolefins 209 with open-chain enamines 210. Seebach and Golinski have further pointed out that several condensation reactions can also be rationalized by using this approach (a) cyclopropane formation from olefin and carbene, (b) Wittig reaction with aldehydes yielding cis olefins, (c) trans-dialkyl oxirane from alkylidene triphenylarsane and aldehydes, (d) ketenes and cyclopentadiene 2+2-addition, le) (E)-silyl-nitronate and aldehydes, (f) syn and anti-Li and B-enolates of ketones, esters, amides and aldehydes, (g) Z-allylboranes and aldehydes, (h) E-alkyl-borane or E-allylchromium derivatives and aldehydes, (i) enamine from cyclohexanone and cinnamic aldehyde, (j) E-enamines and E-nitroolefins and finally, (k) enamines from cycloalkanones and styryl sulfone. 

Scheme 8.8 Mukaiyama aldol reactions of silyl ketene acetals with aldehydes.

Table 11 Reaction of O-silacyclobutyl A/.O-ketene acetals with aldehydes...

Because tin(ll) enolates of thioesters are generated upon reaction of tin(ll) thiolates with ketenes, the optically active p-hydroxy thioesters are also easily synthesized by way of the aldol reaction with aldehydes in the presence of tin(Il) trifluoromethanesulfonate and chiral diamine 1 (eq 7)7... 

This reaction of silyl ketene acetals with aldehydes, using 29 as a stoichiometric chiral reagent (Eq. 46), was reported by Reetz et al. [42]. The aldol addition of l-(trimethyl-siloxy)-l-methoxy-2-methyl-l-propene and 3-methylbutanal provides the aldol in only 57 % yield, but with 90 % ee. 

Evans et al. recently reported the use of structurally well-defined Sn(II) Lewis acids for the enantioselective aldol addition reactions of a-heterosubstituted substrates [47]. These complexes are readily assembled from Sn(OTf)2 and C2-symmetric bis(oxazoline) ligands. The facile synthesis of these ligands commences with optically active 1,2-diamino alcohols, which are themselves readily available from the corresponding a-amino acids. The Sn(II)-bis(oxazoline) complexes were shown to function optimally as catalysts for enantioselective aldol addition reactions with aldehydes and ketone substrates that are suited to putatively chelate the Lewis acid. For example, use of 10 mol % Sn(II) catalyst, thioacetate, and thiopropionate derived silyl ketene acetals added at -78 °C in dichloromethane to glyoxaldehyde to give hydroxy diesters in superb yields, enantioselectivity, and diastereoselectivity (Eq. 27). The process represents an unusual example wherein 2,3-ant/-aldol adducts are obtained stereoselec-tively. 

Another highly fluorinated rare earth y9-diketonate, 21 (Ln = Pr, Eu, Ho dppm = di(perfluoro-2-propoxypropionyl)methanate), showed itself to be a delicate reagent, not only for accomplishing high chemoselectivity in Mukaijama aldol reactions with aldehydes and ketene silyl acetals (KSA) [123], for it was attributed with a mode of stereomodulating catalysis in the aldol reaction of alkoxy aldehydes with KSA (eqs. (12) and (13)). 

Condensations. The reaction of silyl ketene acetals with aldehydes favors enals over saturated aldehydes, when promoted by BUjSnClO. The catalyst is obtained from reaction of trityl perchlorate and tributyltin hydride. 

Exquisite diastereochemical control is attained by tuning the relative bulk of the two alkoxy groups in ketene silyl acetals derived from a-alkoxyacetic esters, during aldol reaction with aldehydes. A chiral version is promoted SiCU in the presence of the phos-photriamide 5. The same set of reaction conditions is also applicable to create asymmetric quaternary carbon centers, for example, in the reaction of Al-silyl ketenimines with ArCHO. °... 

Aldol-type reaction. The low-temperature-catalyzed condensation of O-silyl ketene acetals with aldehydes leads to /3-hydroxy esters. The same catalyst also mediates allylation of aldehydes. 

Catalyzed Mukaiyama-type aldol reactions of silyl enol ethers or silyl ketene acetals with aldehydes lead to the same products. For recent advances see a) G. E. Keck, D. Krishnamurthy, J. Am. Chem. Soc. 1995, 117, 2363 b) M. Sato, S. Sunami, Y. Sugita, C. Kaneko, Heterocycles 1995, 41, 1435, and references therein. 

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