Diastereoselective Temporary Silicon‐Tethered Ring‐Closing‐Metathesis Reactions with Prochiral Alcohols: A New Approach to Long‐Range Asymmetric Induction

Abstract

The ability to control stereochemistry in substrates where the reactive elements are distal represents a fundamentally important area of investigation that is commonly referred to as long-range asymmetric induction. [1,2] Although there are numerous examples of this phenomenon, a significant limitation with this type of process is the ability to predict the manner in which the chiral group attains proximity to the reactive site in order to translate stereochemical information. The inherent challenge associated with this requirement provided the incentive for the development of a new process where the elements of stereocontrol could be conserved in a predictable manner.[1, 2] Herein, we describe a new approach to long-range asymmetric induction using the diastereoselective temporary silicon-tethered (TST) ring-closing-metathesis (RCM) reaction of mixed bisalkoxy silanes 1, derived from an allylic and prochiral alcohol, for the construction of cis-1,4-silaketals 2 (Scheme 1; n = 0). This methodology was also extended to higher homologues (where n = 1-4), which resulted in the formation of the opposite trans diastereoisomer.

Unusual E‐Selective Ring‐Closing Metathesis To Form Eight‐Membered Rings

“…This result was surprising because we had expected the exclusive formation of the Z olefin by analogy to the results of Evans [4] and Harvey. [5] To the best of our knowledge, there is only one reported example of a RCM giving an eightmembered ring that selectively generates an E olefin (Prunet et al).…”

“…[3] In particular, Evans et al reported a diastereomer-discriminating RCM to form Z olefins containing eight-membered rings using silicontethered substrates. [4] Harvey et al also recently applied a similar RCM to the study of natural product synthesis. [5] Herein we report an unusual E-selective RCM to form an eight-membered ring from a silicon-tethered diene, wherein we identified several factors that dictate the preferred formation of the E olefin.…”

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…”

Metathesereaktionen in der Totalsynthese

“…Diese Beobachtung war für die Gruppe wenig überraschend, da ihnen der Aufbau von trans-1,4-Silaketalen durch Ringschlussmetathese bereits zuvor oft Probleme bereitet hatte. [58] Dennoch erhielten sie das cyclisierte (oder gekuppelte) Produkt 20 in guter Ausbeute (83 %), ohne dass unerwünschte Konkurrenzreaktionen an der Alkin-oder der Butenolidgruppe auftraten. Nachdem sie beispielhaft ihre unterschiedlichen Zwecke erfüllt hatten, wurden die drei Silylgruppen von Verbindung 20 durch Einwirkung von Fluorwasserstoff abgespalten.…”