Inter- and Intramolecular [4 + 3] Cycloadditions Using Epoxy Enol Silanes As Functionalized Oxyallyl Cation Precursors

Abstract

Using epoxy enol triethylsilanes as oxyallyl cation precursors, [4 + 3] cycloadditions with various dienes occur under catalysis by silyl triflates and acids in good yields. The intramolecular [4 + 3] cycloaddition proceeds under mild conditions and generate hydroxylated cycloadducts with high diastereoselectivity and yields. Enantiomerically pure epoxy enol silanes have been shown to give excellent yields of the optically pure cycloadduct bearing multiple stereocenters.

Formal Total Synthesis of (+)‐Cortistatins A and J

“…Our studies of this cycloaddition showed that it was both high‐yielding and diastereoselective for the synthesis of carbobicyclic [5.4.0] systems (Scheme ) 8a. Substituents at various positions are compatible, and the absolute stereochemistry of the epoxide determined the facial selectivity of the cycloaddition.…”

“…[4h, 5d, 6f-h] Following our first work on ap artial structure, [6k] herein we report the asymmetric formal total synthesis of cortistatins A( 1)a nd J (2), intercepting advanced intermediates in the Nicolaou-Chen total synthesis [4c-d] and the Yamashita-Hirama total synthesis. [4g] This approach featured ahighly diastereoselectiveintramolecular [4+ +3] cycloaddition of epoxy enolsilanesw ith furan, ar eaction developed in our group, to construct the key oxygenbridged ring Bc oncomitantly with ring C. [7,8] Our synthesis of key cycloaddition precursor 11 commenced from the commercially available cyclopentanedione 4,w hich is destined to be ring Do fc ortistatins Aa nd J, and to serve as the chiral linker to unite the diene and the dienophile for the key intramolecular [4+ +3] cycloaddition. An umber of reactions were examined to achievethe desymmetrizing reduction of cyclopentanedione 4,i ncluding aC BS-reduction, [6k] but asymmetric transfer hydrogenation was ultimately found to be the most robust transformation for scale-up.…”

Ring Expansions of Oxiranes and Oxetanes

“…Professor Chiu has designed a very clever system to form fused ring oxatropane products from electron-rich vinyl oxiranes tethered to furans (Scheme 28) [42]. This approach proceeds via an oxyallyl cation, which engages in an [4+3] cycloaddition with the furan moiety.…”

Five‐Membered Heterocycles: Furan

“…The [4 þ 3] cycloaddition of furans with epoxy enol silane derived oxyallyl cations (Scheme 6.117) has been rendered a viable process by optimization of the reaction conditions and use of a bulky triethylsilyl group [233]. Dioxines were used as oxyallyl cation equivalents in a Au/Ag-catalyzed [4 þ 3] cycloaddition with furan [234].…”