Solvent-Dependent Divergent Functions of Sc(OTf)₃ in Stereoselective Epoxide-Opening Spiroketalizations

Abstract

A stereocontrolled synthesis of benzannulated spiroketals has been developed using solvent-dependent Sc(OTf)3-mediated spirocyclizations of exo-glycal epoxides having alcohol side chains. In THF, the reaction proceeds via Lewis acid catalysis under kinetic control with inversion of configuration at the anomeric carbon. In contrast, in CH2Cl2, Brønsted acid catalysis under thermodynamic control leads to retention of configuration. The reactions accommodate a variety of aryl substituents and ring sizes and provide stereochemically diverse spiroketals.

A Divergent Enantioselective Strategy for the Synthesis of Griseusins

“…In contrast, the same reaction in the presence of InCl 3 in THF led to the corresponding 1,3′- epi -griseusin C precursor 18 (59% yield, 73:27 d.r.). Distinct from previous examples, [16c,d] diastereoselectivity may derive from facial selectivity of 16 epoxidation (TfOH predominantly si -face; InCl 3 re -face bias), in which the sequential cyclization follows a C 1 -inversion mechanism in both cases. For all products, the relative configuration at newly generated stereocenters was assigned by cross peaks in NOESY and other 2D NMR spectra (Scheme 3).…”

“…While few, if any, examples exist of sequential unsaturated ketone epoxidation and cyclization, the seminal work of Tan and co-workers on the stereoselectivity of allyl silyl ether-based spiroketal formation served as a basis for this strategy. [16] Subsequent screening of a range of oxidants, solvents, and Lewis or Brønsted acids revealed that the addition of dimethyldioxirane (DMDO) [17] to a 1:1 mixture of 16 and TfOH in DCM afforded the desired griseusin C-type precursor 17 (80% yield, > 98:2 d.r., Tables S6 and S7). In contrast, the same reaction in the presence of InCl 3 in THF led to the corresponding 1,3′- epi -griseusin C precursor 18 (59% yield, 73:27 d.r.).…”

Introduction of Boron Functionalities into Silsesquioxanes: Novel Independent Methodologies

“…[67][68][69][70][71][72] Therefore, an umber of experiments were performed to ascertain which specie-triflate salt or in situ formed acid-was at rue catalysti nt his transformation.D uring the course of our study, the difference in activity of Lewis acid (Sc(OTf) 3 )a nd Brønsted acid (TfOH) as catalysts in O-borylation of incompletely condensed POSS trisilanol were also investigated to unearthw hich specie was the active catalytic. Again, the only by-product formed in this reaction was an eutrala nd harmless isobutylene.…”

“…It is well known, that a metal triflate can serve as as ource of the hidden Brønsted acid (triflic acid), which may be generatedi ns itu via hydrolysis. [67][68][69][70][71][72] Therefore, an umber of experiments were performed to ascertain which specie-triflate salt or in situ formed acid-was at rue catalysti nt his transformation.D uring the course of our study, the difference in activity of Lewis acid (Sc(OTf) 3 )a nd Brønsted acid (TfOH) as catalysts in O-borylation of incompletely condensed POSS trisilanol were also investigated to unearthw hich specie was the active catalytic. First, the performance of the same loading of pure TfOH (4 mol %), insteado fS c(OTf) 3 ,w as checked as the catalyst in the O-borylation of POSS trisilanol.…”

Stereocontrolled Synthesis of Spiroketals: An Engine for Chemical and Biological Discovery

“…28 From salicylaldehydes 63 , alkyne additions afforded propargyl alcohols 64 . Au(I)-mediated cycloisomerizations 29 yielded exo -glycals 65 .…”