Temporary Silicon–Tethered Ring–Closing Metathesis Reactions in Natural Product Synthesis

Phosphate‐Tether‐Mediated Ring‐Closing Metathesis for the Preparation of Complex 1,3‐anti‐Diol‐Containing Subunits

“…In contrast to the elegant diastereoselective RCM studies by Evans and coworkers 7 using Si-tethered dienes where only cis- substituted 7-membered products were observed, RCM of phosphate trienes 18 and 20 , yielded both 7-membered products trans- 19 and cis- 21 , albeit with different reaction rates and catalyst loadings (Scheme 4). In addition, the cis -diastereomer reacted at a much faster rate and with better yields.…”

“…This stands in contrast to seminal works by Evans, Kobayashi, and others that have provided insight on the behavior of silicon tethers to RCM in a variety of systems. [4,7] Inspired by this shortcoming, as well as a surprising inability to access the targeted key fragment en route to the synthesis of dictyostatin ( 1 ) (Scheme 1), vide infra , ongoing efforts in our lab have focused on the exploration of phosphate-tether reactivity profiles across a spectrum of substrates. We herein report the preliminary results of a detailed study highlighting the stereochemical factors involved in phosphate tether-mediated diastereotopic differentiation of 1,3- anti -diol subunits (Figure 1).…”

A highly convergent synthesis of the C1–C31 polyol domain of amphidinol 3 featuring a TST-RCM reaction: confirmation of the revised relative stereochemistry

“…The masked syn -1,5-tetraol 3 would in turn be prepared by the alkylation of the Weinreb amide 6 with an organometallic reagent derived from the vinyl iodide 5 followed by an enantioselective reduction of the resulting ketone. The preparation of the cyclic silaketal 4 , which constitutes the aforementioned polyacetate/polypropionate type domain, relies on a Z -selective TST-RCM reaction for coupling 7 and 8 with concomitant diastereoselective hydroboration to facilitate the construction of the C23–C24 stereocenters using medium-ring stereocontrol 11,12…”

“…The preparation of the cyclic silaketal 4 , which constitutes the aforementioned polyacetate/polypropionate type domain, relies on a Z -selective TST-RCM reaction for coupling 7 and 8 with concomitant diastereoselective hydroboration to facilitate the construction of the C23–C24 stereocenters using medium-ring stereocontrol. 11 , 12 …”

Phosphate tether-mediated ring-closing metathesis for the generation of medium to large, P-stereogenic bicyclo[n.3.1]phosphates

“…1,2 In this regard, olefin metathesis, 3 in combination with temporary tether strategies (i.e. silicon, 4,5,6 ketal, 7 carboxylate, 8 etc. ), has provided an elegant solution to the coupling of complex tether-partners, under mild reaction conditions, to provide small, medium, and large rings.…”