Tetrasubstituted ketene acetals

Yet another version of the Zr-catalyzed Mannich process developed by the Kobayashi group is summarized in Scheme 6.29 [78], In this instance, the chiral catalyst (94) is proposed to bear a single binol molecule, where the 2,2 -dibromobinol proves to be the superior choice. Once again, protic additives, particularly H20, prove to be beneficial (see Scheme 6.29). This particular class of catalytic C—C bond formations is not limited to tetrasubstituted ketene acetals as illustrated in Scheme 6.29, less substituted thioace-tals prove to be effective reaction partners as well. 

Further investigation with various silyl ketene acetals is summarized in Table 6. Silyl ketene acetals derived from various esters were reacted with /V-benzyloxy-carbonylamino sulfones 1 in the presence of 0.5-1 mol% Bi(0Tf)3-4H20. The corresponding (3-amino esters 24 were obtained in moderate to good yields (Table 6). Silyl enolates derived from esters as well as thioesters reacted smoothly to give the adducts. The /V - be n z v I o x v c ar bo n v I a m i n o sulfone derived from n-butvraldehyde lp led to moderate yields of (3-amino esters when reacted with (thio)acetate-derived silyl ketene acetals (Table 6, entries 1 and 2). A very good yield was obtained when the same sulfone was subjected to a tetrasubstituted silyl ketene acetal (Table 6, entry 3). The latter afforded moderate to good yields of (3-amino esters 24 with phenylacetaldehyde, / -tolu aldehyde, and o-tolualdehyde-derived sulfones (Table 6, entries 4-6). 

In spite of the impressive variety of studies on the Ireland-Claisen rearrangement, several significant Hmitations to the reaction remain. A general solution to the problem of stereocontrolled formation of Cl,Cl-disubstituted silyl ketene acetals has yet to be reported. There is as yet no general catalytic enantioselective variant of the Claisen rearrangement There are as yet no reports of stereoselective generation of acyclic tetrasubstituted alkenes. 

Cycloaddition of dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate with EWG-substituted primary ketene N,0-acetals provides a tetrasubstituted pyridazine, methyl 4-amino-5,7-dioxo-6,7-dihydro-5/7-pyrrolo[3,4-4pyridazine-3-carboxylate <200681513>. 

A route involving annulation of ketene-AiA-acetals has been developed, as illustrated by the transformation of the substrate 143 into the tetrasubstituted pyrrole 144 (Equation 41). This methodology was used for the synthesis of some key pyrrole intermediates toward the alkaloids lukianol A and lamellarin Q <2005TL475>. 

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