Spirotryprostatin 1,3-dipolar cycloaddition

Azomethine ylides derived from (55,6/ )-2,3,5,6-tetrahydro-5,6-diphenyl-1,4-oxazin-2-one (53) and various aldehydes have been prepared by Williams and co-workers (87,88) (Scheme 12.19). In a recent communication they reported the application of the azomethine ylide 54 in the asymmetric total synthesis of spirotryprostatin B 56 (88). The azomethine ylide 54 is preferentially formed with ( )-geometry due to the buLkiness of the aldehyde substituent. The in situ formed azomethine ylide 54 reacted with ethyl oxindolylidene acetate to give the 1,3-dipolar cycloaddition adduct 55 in 82% yield as the sole isomer. This reaction, which sets four contiguous stereogenic centers, constmcts the entire prenylated tryprophyl moiety of spirotryprostatin B (56), in a single step. 

Sebahar, P.R. et al.. Asymmetric, stereocontroUed total synthesis of (+) and (-)-spirotryprostatin B via a diastereoselective azomethine ybde [l,3]-dipolar cycloaddition reaction. Tetrahedron, 58, 6311, 2002. 

M. N. Cheng, H. Wang, L.-Z. Gong, Org. Lett. 2011, 13, 2418-2421. Asymmetric organocatalytic 1,3-dipolar cycloaddition of azomethine ylide to methyl 2-(2-nitrophenyl)acrylate for the synthesis of diastereoisomers of spirotryprostatin A. 

Williams has reported a MCR in the synthesis of spirotryprostatin B 50, a spirooxindole-substituted diketo-piperazine with a prenylsubstituent at C-18 (Scheme 6.7). In the key step, diphenylmorphoUnone 66 reacts with isovaleraldehyde 67 to form azomethine ylide 69, which is attacked by the oxindole 68 to build the latter 70 in a [3+2]-dipolar cycloaddition [24]. 

The spirocyclic oxindole core structure was constructed by an asymmetric 1,3-dipolar cycloaddition in the total synthesis of (—)-spirotryprostatin B. A reaction of oxazi-none 137 with aldehyde 138 and oxindole 139 resulted in spirooxindole 141 via the chiral azomethine yhde 140, simultaneously creating three bonds and four stereogenic centers in one step (Scheme 16.20). ... 

SCHEME 16.20. An asymmetric 1,3-dipolar cycloaddition used for the synthesis of (—)-spirotryprostatin B. 2000 American Chemical Society. All rights reserved. 

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