ContentsI. Introduction 31 II. Background 32 A. Addition of Crotylstannanes to Aldehydes 32 B. γ-Silyloxy and Alkoxy Allylic Stannanes 32 III. Enantioenriched R-Alkoxy Allylic Stannanes 33 A. Synthesis 33 B. Additions to Achiral Aldehydes 33 C. Additions to Chiral Aldehydes 35 IV. Enantioenriched γ-Alkoxy and γ-Silyloxy Allylic Stannanes 35 A. Synthesis 35 B. Additions to Achiral Aldehydes 36 C. Additions to R-Alkoxy Aldehydes 38 D. Additions to R-Amino Aldehydes 39 V. Transmetalations 40 A. With SnCl 4 40 B. With InCl 3 41 VI. Allenic Stannanes 42 A. Synthesis 42 B. Additions to Achiral Aldehydes 42 C. Additions to Chiral Aldehydes 42 D. Transmetalations with SnCl 4 43 VII. Propargylic Stannanes 44 A. Synthesis 44 B. Additions to Aldehydes 45 VIII. Future Directions 45 A. Chiral Catalysis 45 B. γ-Functionalized R-Alkoxy Allylic Stannanes 46 IX. Conclusions 46 R-position) aldehyde.

No abstract

The total synthesis of (+)-discodermolide is described. The approach involves assemblage of three key stereotriad subunits through addition of nonracemic allenyltin, -indium, and -zinc reagents to (S)-3-silyloxy-2-methylpropanal derivatives, followed by reduction of the resulting anti,syn- or syn,syn-homopropargylic alcohol adducts to the (E)-homoallylic alcohols and subsequent Sharpless epoxidation. Addition of methyl cuprate reagents or Red-Al to the resultant epoxy alcohols yielded the key precursors, alkyne 4, aldehyde 9, and alcohol 24. Addition of alkyne 4 (as the lithio species 10) to aldehyde 9 afforded the propargylic alcohol 11 as the major stereoisomer. Lindlar hydrogenation and installation of appropriate protecting groups led to aldehyde 17. This was converted to the (Z)-vinylic iodide 18 upon treatment with α-iodoethylidene triphenylphosphorane. Suzuki coupling of this vinylic iodide with a boranate derived from iodide 25 led to the coupled product 27 with the complete carbon backbone of (+)-discodermolide and the correct stereochemistry. The synthesis was completed by cleavage of the cyclic PMP acetal at C1 with i-Bu2AlH and three-step oxidation−esterification to the ester 31. Cleavage of the C19 Et3Si ether and C19 carbamate formation followed by cleavage of the remaining alcohol protecting groups, first with DDQ and then aqueous HCl, afforded (+)-discodermolide (36).

ChemInform Abstract (39 refs.).

This account traces the evolution of our work on the synthesis of chiral allylic and allenic organometal compounds of tin, silicon, zinc, and indium and their application to natural product synthesis over the past quarter century.