Ladder Polyether Synthesis via Epoxide-Opening Cascades Directed by a Disappearing Trimethylsilyl Group

Abstract

Epoxide-opening cascades offer the potential to construct complex polyether natural products expeditiously and in a manner that emulates the biogenesis proposed for these compounds. Herein we provide a full account of our development of a strategy that addresses several important challenges of such cascades. The centerpiece of the method is a trimethylsilyl (SiMe 3 ) group that serves several purposes and leaves no trace of itself by the time the cascade has come to an end. The main function of the SiMe 3 group is to dictate the regioselectivity of epoxide opening. This strategy is the only general method of effecting endo-selective cascades under basic conditions.

One‐Pot Synthesis of 2,7‐Dioxabicyclo[2.2.1]heptanes from Oxoallylsilanes

“…Jamison and co-workers [26] have reported that the regiochemical outcome of the cyclization of poly(α,β-silyl epoxides) is dependent on the nature of the catalyst used and the number of silyl epoxide units on the substrate.…”

Synthetic and biosynthetic methods for selective cyclisations of 4,5-epoxy alcohols to tetrahydropyrans

“…Jamison used this chemistry to good effect in iterative cascades, creating fused THP rings in excellent stereoselectivities and yields (Scheme 17). 56,57 It was found that while BF 3 •Et 2 O was effective in the synthesis of isolated tetrahydropyrans, poor selectivity was obtained in cascade reactions. In contrast, the use of mildly basic conditions (Cs 2 CO 3 and CsF in MeOH) facilitated the formation of fused THPs with concomitant deprotection of the silyl directing groups via a homo-Brook rearrangement (Scheme 17).…”

Ring Expansions of Oxiranes and Oxetanes

“…This section covers recent contributions toward accessing multiple oxygen heterocycles via oxirane-initiated ring-expansion cascades. In 2006, Professor Jamison reported how a strategically placed oxirane silyl substituent could serve the role of a traceless directing group to form fused Scheme 10 Carbonylation of cis-epoxides to give enantioenriched and desymmetrized β-lactones tetrahydropyran products (Scheme 11) [13,14]. All the ethereal ring junctions in this creative cascade are trans to each other.…”