Total Syntheses of (−)-Grandinolide and (−)-Sapranthin by the Sharpless Asymmetric Dihydroxylation of Methyltrans-3-Pentenoate: Elucidation of the Stereostructure of (−)-Sapranthin

Abstract

Methyl trans-3-pentenoate (7) was converted into the cis-substituted g-lactone 8 in a single step with 78 % ee. The derived enolate dilithio-8 was alkylated trans-selectively with primary iodoalkanes. with 1-iodobutane dilithio-8 afforded, after esterification with isovaleroyl chloride, the epi-blastmycinone 9. Dilithio-8 gave (À)-grandinolide (11) with 1-iodo-19-phenylnonadecane (20). A third trans-selective alkylation of dilithio-8 was undertaken with 16-iodo-1,5-hexadecadiene-7,9-diyne (21). This gave the g-lactone 12, which had the published relative configuration of (À)-sapranthin but different spectroscopic data. When the OH group of lactone 8 was inverted (to hydroxylactone 40) and the derived enolate dilithio-40 alkylated with iodide 21, lactone 41 resulted. Its 1 H and 13 C NMR spectra and the sign and value of optical rotation coincide with the data of natural sapranthin. These findings establish that (À)-sapranthin possesses the relative and absolute configuration of stereoformula 41.

A New Strategy for the Synthesis of Himbacine

“…15 We used racemic diester 7 in the hope that kinetic resolution might be achieved in the reaction with the enantioenriched Michael acceptor. Addition of two equivalents of racemic diester 7 to enantioenriched butenolide 21, followed by in situ Dieckmann reaction, gave tricyclic product 22 (46%), 16 along with two minor diastereoisomers 23 (10%) and 24 (18%).…”

Nonracemic γ‐Lactones from the Sharpless Asymmetric Dihydroxylation of β,γ‐Unsaturated Carboxylic Esters

“…Similarly, Harcken and Rank accomplished a total synthesis of (–)‐grandinolide ( 179 , Scheme ) . Most of the effort went into synthesizing 1‐iodo‐19‐phenylnonadecane ( 178 ).…”

“…Harcken's and Rank's structure‐proving total synthesis of (–)‐sapranthin ( 195 ) . Reagents and conditions : (a) NEt 3 (2.1 equiv.…”

A Practical Domino‐Claisen–Cope Sequence in the Synthesis of New Blooming Citrus and Potent Floral Rose Alcohols

“…) . Several related Ireland – Claisen–Cope and para ‐ Claisen–Cope sequences with aromatic substrates were also described.…”