Controlled diastereoselection in 2-lithio-1,3-dithiane additions onto α-substituted γ-lactols. Model studies toward bryostatins from (R)-pantolactone

Abstract

RENB ROY and ALLAN W. REY. Can. J. Chem. 69, 62 (1991). Homochiral a-substituted y-lactols 3 and 4 derived from (R)-pantolactone 1 were used in 2-lithio-1,3-dithiane additions to afford very high controls in diastereoselectivities arising from 1,2-asymmetric inductions. Thus non-chelation controlled nucleophilic addition on 3 gave the anti diastereomer 5 as the major product (92% de), while the chelation controlled addition on 4 furnished the syn diastereomer 7 (96% de) as the almost exclusive product. The stereochemical outcomes of these reactions were proven unambiguously by locking the conformation of the syn-and anti-trio1 adducts 7 and 8 through their respective acetonides and by nuclear Overhauser enhancement measurements. The lack of 1,3-dioxolane formation in the case of the anti-trio1 8 was taken as a further confirmation of the absolute configuration at the newly created stereocenter.Key words: byrostatin, pantolactone, a-hydroxylactol, dithiane.RENB ROY et ALLAN W. REY. Can. J. Chem. 69, 62 (1991). Les y-lactols homochirals 3 et 4 a-substituts dtrivts de la (R)-pantolactone 1 ont Ctt utilisCs dans des rtactions d'additions avec le carbanion lithit du 1,3-dithiane pour fournir un trks haut contr6le diasttrtostlectif provenant d'une induction asymttrique-1,2. Le sttrtocontr6le de I'addition nucltophilique sur 3 en l'absence de phtnomkne de chtlatation a donne le diastertomkre anti 5 c o m e produit majeur tandis que la chtlatation cornrne moyen de sttrtocontr6le de I'addition nucltophilique sur 4 a conduit presque exclusivement au diasttrtomkre syn 7 c o m e produit final. Les rtsultats sttriochimiques de ces rtactions ont t t t prouvts de f a~o n non-ambigiie en fixant la conformation des adduits syn-et anti-trio1 7 et 8 par la formation de leurs dtrivts acttals respectifs et par des mesures d'effets nOe. L'absence de formation de 1,3-dioxolane dans le cas du triol-anti 8 a t t i considtrte comme preuve suppltmentaire de la configuration absolue au nouveau centre sttrtogtnique form6 .Mots cle's : byrostatine, pantolactone, a-hydroxylactol, dithiane. IntroductionDuring synthetic endeavors (1-3) toward the construction of the antineoplastic macrolides bryostatins (4), chiral fragments containing quaternary gem-dimethyl carbon centers were required. Within the chiral pool, (R)-pantolactone 1 was sought as a useful chiral template. As such, 1 has scarcely been utilized for the enantiomeric synthesis of complex natural products (5, 6). On the other hand, 1 and its (S)-enantiomer (7) have received increased interest as chiral auxiliaries in asymmetric Diels-Alder cycloadditions (7,8) and in diastereoselective ketene protonations (9).Although there have been numerous examples of 1,2-induction in acyclic stereoselections (lo), examples of similar or remote inductions in y-or 6-lactols have received limited attention (1 1). We wish to describe herein the results obtained with 2-lithio-l,3-dithiane additions onto a-substituted y-lactols. The effects of 1,2-chelation and non-chelation on the diastereoselectivitie...

Collective Synthesis of Humulanolides Using a Metathesis Cascade Reaction

“…The synthesis began with the asymmetric preparation of tetraene 21 (Scheme ). The Wittig olefination of the readily available starting material 16 gave known diol 11 {[α] D 26 −23.5 ( c 2.0, CHCl 3 ); lit . [α] D 25 −20.5 ( c 0.74, CHCl 3 )}, which was oxidized with TEMPO/BAIB to give aldehyde 17 in 75% yield (22.1 g scale).…”

Ruthenium-Catalyzed Metathesis Cascade Reactions in Natural Products Synthesis

“…Our synthetic work started with the commercial available compound D‐pantolactone, which was subjected to sequential reduction and Wittig olefination reaction to give the known diol 96 , which was oxidized with TEMPO/BAIB to give aldehyde 97 in 75 % yield (22.1 g scale). Aldehyde 97 was found to be unstable under basic conditions, but reacted cleanly with the Wittig reagent 98 to give the desired diene 99 in 75 % yield (13.0 g scale).…”