Stereoselective Syntheses of Enantiomerically Pure 2,5-disubstituted Dihydropyrans Based on Olefin Metathesis

Abstract

A short synthesis of 2,5-disubstituted dihydropyrans starting from d-mannitol as a chiral building block is described. Our synthetic approach combines ruthenium-catalyzed ring closing olefin metathesis and palladium-catalyzed nucleophilic substitution.

Synthesis of Dihydrofurans and Dihydropyrans with Unsaturated Side Chains Based on Ring Size‐Selective Ring‐Closing Metathesis

“…Such a sequence is a convenient entry into the stereoselective synthesis of 2,5-cisdisubstituted dihydropyrans. [69,70] …”

Desymmetrization of (R,R)-Hexa-1,5-diene-3,4-diol via Monofunctionalization and Rhodium-Catalyzed Allylic Substitution

“…Polar functional groups, in particular protic groups, often exert a significant effect on the reactivity and selectivity of transition metal-catalyzed reactions . Therefore, we also included the unprotected carbonates 3g and 3h in this study. These were selectively synthesized from diol 1 and anhydrides 6a , b , respectively, using Clarke’s method .…”

“…The title compound was obtained from 1 (5.00 g, 43.2 mmol) and Boc 2 O (6a, 87.6 mmol, 19.7 g) following the previously published procedure. 19 Yield of 3g: 8.00 g (85%). All analytical data match those previously reported in the literature.…”

“…Over the past few years, we − and others − reported a number of examples for the successful application of the C 2 -symmetric building block 1 or ent - 1 in stereoselective synthesis. Normally, a desymmetrization of 1 is required, which is in most cases achieved by selective monofunctionalization, e.g.…”

Ring-Size-Selective Enyne Metathesis as a Tool for Desymmetrization of an Enantiopure C2-Symmetric Building Block

“…In this Note we present results that indicate not only a remarkable rate-accelerating but also a strong selectivity-controlling effect of an allylic alcohol in ring-closing enyne metathesis reactions. This work was inspired by ongoing target molecule projects in our group, which aim at the enantioselective synthesis of natural products with a 2,5-disubstituted tetrahydropyran core . The envisaged enantiomerically pure starting materials are either the C 2 -symmetrical hexadienediol 1 , , conveniently available from d -mannitol, or ent - 1 , which is synthesized from l -tartrate.…”