A Systematic Study of Functionalized Oxiranes as Initiating Groups for Cationic Polycyclization Reactions

Abstract

Three different methods have been developed that effectively utilize chiral oxiranes derived from Katsuki-Sharpless epoxidation of allylic alcohols as initiating groups for cationic cyclization of unsaturated substrates to form chiral polycycles. This type of transformation has previously been problematic. These employ either epoxy-methoximes, vinyl-substituted oxiranes, or hydroxymethyl oxiranes. All three approaches are described in detail. In addition, this research has led to possible explanations for previously encountered difficulties in this area and provided two new insights into the Lewis acid activation of oxiranes. The methodology described herein constitutes a valuable link between two powerful synthetic constructions, enantioselective Katsuki-Sharpless epoxidation and cationic polycyclization reactions.

Tetraphenylphosphonium Tetrafluoroborate/1,1,1,3,3,3-Hexafluoroisopropanol (Ph4PBF4/HFIP) Effecting Epoxide-Initiated Cation–Olefin Polycyclizations

“…The one-step epoxide-initiated cation–olefin polycyclization of ( 3S )-2,3-oxidosqualene ( 1 ), a linear epoxy polyene, to form the polycyclic steroid lanosterol ( 2 ) is efficiently catalyzed by enzymes in living systems (Scheme ). Mimicking this process has long interested synthetic organic chemists . Pioneering work by Goldsmith and van Tamelen revealed that BF 3 ·Et 2 O catalyzes epoxide-initiated cation–olefin polycyclizations .…”

Recent Developments in Polyene Cyclizations and Their Applications in Natural Product Synthesis

“…A systematic study of using functionalized unsaturated oxiranes in Lewis acid mediated polyene cyclization was published by Corey and co-workers, providing valuable insight into the electronic effects of neighboring substituents in epoxide initiated cationic π-cyclizations (Scheme 5). 10 A. G. M. Barrett et al…”

“…Utilizing the same strategy, (-)-5epi-aureol (35) was also synthesized via alcohol 34 (91%), which was prepared from aryl enol ether 33. 10 Chang and co-workers reported that tin(II) triflate catalyzed the polyene cyclization of β-keto sulfones (Scheme 8). 13 It was found that this Lewis acid could catalyze the cy-…”

Total Synthesis of Antiproliferative Parvifloron F

“…Cyclization of 4 was successfully accomplished by the use of tin­(IV) chloride as a Lewis acid at room temperature to provide the desired product 10 in good yield (Scheme ). Other Lewis acids, such as boron trifluoride diethyl etherate and titanium­(IV) chloride, were tested under various conditions for the cyclization of (±)- 4 , which was prepared separately.…”