2,6-Disubstituted Tetrahydropyrans by Domino Meyer-Schuster Rearrangement-Hetero-Michael Addition of 6-Alkyne-1,5-diols

Abstract

LETTER 1523 2,6-Disubstituted Tetrahydropyrans by Domino Meyer-Schuster Rearrangement-Hetero-Michael Addition of 6-Alkyne-1,5-diols S y n t h e s i s o f 2 , 6 -D i s u b s t i t u t e d T e t r a h y d r o p y r a n s Abstract: Starting from pentanediol various oct-6-yne-1,5-diols were prepared. In the presence of catalytic amounts of an Au(I) or Pt(II) catalyst transformation to cis-2,6-tetrahydropyrans was observed. It is assumed that this novel domino sequence proceeds via an initial Meyer-Schuster rearrangement of the propargylic alcohol yielding a hydroxyenone that undergoes an intramolecular oxaMichael addition through a chairlike transition state to the tetrahydropyran system.

An Efficient Stereoselective Synthesis of cis-2,6-Disubstituted Tetrahydropyrans via Gold-Catalyzed Meyer–Schuster Rearrangement/Hydration/oxa-Michael Addition Sequence

“…For example, heating propargylic alcohols 1 with an oxophilic gold (III) catalyst (5 mol% AuBr 3 ) results in cyclization to afford cyclic ethers 4 bearing an acetylene moiety due to activation of the propargylic position by coordination (a) of gold (III) (Scheme 1, route A) [16]. On the other hand, in the presence of a π-philic gold (I) catalyst (2 mol% Ph 3 PAuNTf 2 ), propargylic alcohols 1 undergo Meyer-Schuster rearrangement [19,20] to afford α,β-unsaturated ketones 7, which in turn undergo gold (III)-catalyzed intramolecular oxa-Michael addition [21][22][23][24] to afford cyclic ethers 10 bearing a carbonyl group [16]. In this case, the Meyer-Schuster rearrangement reaction involves activation of the triple bond by coordination (b) of gold (I), and the subsequent addition reaction involves activation of the carbonyl group by coordination (c) of gold (III) (Scheme 1, route B).…”