Four-Step One-Pot Catalytic Asymmetric Synthesis of Polysubstituted Tricyclic Compounds: Lipase-Catalyzed Dynamic Kinetic Resolution Followed by an Intramolecular Diels–Alder Reaction

Abstract

Starting from readily available tertiary alcohols, four different reactions (a 1,3-migration of a hydroxy group, kinetic resolution, racemization, and an intramolecular Diels–Alder reaction) took place under co-catalysis by lipase and oxovanadium compounds in a one-pot process to produce polysubstituted tricyclic carbon frameworks in high yields and with high enantioselectivities. The key to the success of this process was the discovery that a silyl group attached to the terminal carbon of the vinyl moiety completely controls the direction of hydroxy group migration

Lipase/H2SO4‐Cocatalyzed Dynamic Kinetic Resolution of Alcohols in Pickering Emulsion

“…Compartmentalization by immobilizing racemization catalysts and/or lipases inside mesoporous materials has also been reported, [24–26] including our original mesoporous silica‐supported oxovanadium catalyst (V‐MPS4), in which an oxovanadium species was covalently bound to the surface of the 4‐nm‐sized pores in mesoporous silica [27–29] . However, although highly compatible with lipases, V‐MPS4 is prone to side reactions such as ether formation during the racemization process [30–33] . In addition, its racemization profile is limited by the electronic nature of the substrates, with slow racemization observed for simple 1‐phenylethanol ( 1 a : R 1 =Ph, R 2 =Me, Table S2).…”

“…[27][28][29] However, although highly compatible with lipases, V-MPS4 is prone to side reactions such as ether formation during the racemization process. [30][31][32][33] In addition, its racemization profile is limited by the electronic nature of the substrates, with slow racemization observed for simple 1-phenylethanol (1 a: R 1 = Ph, R 2 = Me, Table S2).…”

Expanding the Synthetic Toolbox through Metal–Enzyme Cascade Reactions

“…In a subsequent contribution, a lipase−oxovanadium combination was implemented to perform the DKR of a series of cyclic tertiary allylic alcohols followed by an intramolecular Diels−Alder transformation to synthesize tricyclic compounds in a diastereoselective manner (Scheme 13a). 56 The key of this one-pot process was the use of an α,β-unsaturated ester as an acylating agent in the lipase-catalyzed reaction, so this intermediate further reacted in order to provide the desired product. Thus, after reaction optimization, CAL-B and VO(OSiPh 3 ) 3 were selected as the most suitable catalysts in dichloromethane at 35 °C.…”

Predicting the Conformation of Organic Catalysts Grafted on Silica Surfaces with Different Numbers of Tethering Chains: The Silicopodality Concept

“… 12 − 17 Even more interesting is the possibility of using active inorganic surfaces, for instance silica with suitable concentrations of silanol groups, or silica–alumina surfaces with Brönsted and Lewis acid sites, which can in turn act as cocatalysts in cascade reactions. 18 − 22 …”

“…Hybrid catalysts, formed by organic moieties anchored onto inorganic matrices, are interesting for their capacity to combine enormous varieties of organic functional groups with a solid support with superior mechanical and thermal stabilities. − Such materials offer the advantages of homogeneous catalysis, as high yields, selectivities and possible stereoselectivity, along with those of heterogeneous catalysis, with easily separable products, reduced volume of solvents and so on. − Even more interesting is the possibility of using active inorganic surfaces, for instance silica with suitable concentrations of silanol groups, or silica–alumina surfaces with Brönsted and Lewis acid sites, which can in turn act as cocatalysts in cascade reactions. − …”