Phosphate-tether-mediated ring-closing metathesis for the preparation of complex 1,3-anti-diol-containing subunits

Abstract

An array of examples of diastereoselective, phosphate-tether-mediated ring-closing metathesis reactions, which highlight the importance of product ring size and substrate stereochemical compatibility, as well as complexity, is reported. Studies focus primarily on the formation of bicyclo[n.3.1]phosphates, involving the coupling of C₂-symmetric dienediol subunits with a variety of simple, as well as complex, alcohol partners.

Figure 1

C₂-symmetric 1,3-anti-diol substrates

Figure 2

Proposed transition states and accessible products.

Scheme 1

Proposed retrosynthesis of dictyostatin via a phosphate tether-mediated desymmetrization approach.

Scheme 2

RCM to bicyclo[5.3.1]phosphate intermediates en route to key fragments of dictyostatin.

Scheme 3

RCM to bicyclo[7.3.1]phosphate intermediates en route to key fragments of dictyostatin.

Scheme 4

Bicyclo[4.3.1]phosphate series.

Scheme 5

Kinetic control to bicyclo[4.3.1]phosphate.

Scheme 6

Bicyclo[5.3.1]phosphate series.

Scheme 7

Effect of methyl substitution in RCM to bicyclo[5.3.1]phosphates.

Scheme 8

Experimental confirmation for above proposed intermediate exo,endo-H.

Scheme 9

RCM to bicyclo[5.3.1]phosphates with homologated 1,3-anti-dienediol.