Recent Advances in Stereoselective [2+2+2] Cycloadditions

Abstract

The [2+2+2] cycloaddition reaction is considered one of the most efficient methods for the rapid and straightforward preparation of complex polycyclic (and heterocyclic) compounds in a highly selective and atom‐economical fashion. Over the last half‐century, remarkable advances in terms of chemo‐ and regioselectivities have been realized, endowing this reaction with attractive features as a key step in the synthesis of various biologically active molecules and materials. The development of stereoselective methodologies is more recent. In this field, asymmetric transition‐metal catalysis has emerged as the most convenient tool with which to perform these [2+2+2] cycloadditions in their enantio‐ and diastereoselective variants. All the catalytic systems that have been developed so far are based on very close association of a transition metal (Co, Ni, Ir, Rh, ...) with a chiral ligand. The success of these reactions is then related to the reaction pattern involved (inter‐ and intramolecular), implying an efficient substrate/active species interaction. Thus, judicious design both of chiral ligands and of unsaturated substrates is necessary. In light of these aspects, numerous stereoselective cycloadditions have been reported; these allow the construction in one‐step fashion of central, axial, planar, and helical chiralities. This review details the recent advances in this area, with specific attention to catalysts and reaction scope.

Rhodium‐Catalyzed [2+2+2] Cycloaddition Reactions of Linear Allene–Ene–Ynes to afford Fused Tricyclic Scaffolds: Insights into the Mechanism

“…This was based on the nucleophilic substitution of bromoallyl derivatives (1) with N-tosylallenes (2)u sing potassium carbonatea sabase in refluxing acetonitrile (Scheme 2). This was based on the nucleophilic substitution of bromoallyl derivatives (1) with N-tosylallenes (2)u sing potassium carbonatea sabase in refluxing acetonitrile (Scheme 2).…”

“…1 Ha nd 13 CNMR spectra were measured on a4 00 or a3 00 MHz NMR spectrometer. All reactions requiring anhydrous conditions were conducted in oven-dried glassware under ad ry nitrogen atmosphere.…”

“…The transition-metal-catalyzed [2+ +2+ +2] cycloaddition reaction of three unsaturated partners [1] offers efficient, atom-economical pathwayst oavariety of complex carbocyclic and heterocyclic derivatives. The transition-metal-catalyzed [2+ +2+ +2] cycloaddition reaction of three unsaturated partners [1] offers efficient, atom-economical pathwayst oavariety of complex carbocyclic and heterocyclic derivatives.…”

Unpredictable cycloisomerization of 1,11-dien-6-ynes by a common cobalt catalyst

“…In particular, cycloisomerization of enynes allows one to prepare compounds with exocyclic double bonds and cyclopropanes in a highly selective manner [5–7]. While catalytic transformations of enynes have been investigated in detail, there are only a few examples of similar reactions of dienynes [8–14].…”

Asymmetric Synthesis of Protected Cyclohexenylamines and Cyclohexenols by Rhodium‐Catalyzed [2+2+2] Cycloaddition

“…[3] In 2005, the groups of Evans and Shibata independently reported the rhodium(I)catalyzed enantioselective [2+ +2+ +2] cycloaddition of 1,6enynes with alkynes. [5][6][7][8][9] We anticipated that if high reactivity and selectivity of the reactions using acrylamides arise not from their electron-deficient nature but high coordination ability, highly coordinative electron-rich enamides [10] would also be suitable cycloaddition partners toward 1,6-enynes.Herein, we disclose the cationic rhodium(I) complex catalyzed regio-, diastereo-, and enantioselective [2+ +2+ +2] cycloaddition of 1,6enynes (1)with enamides and vinyl carboxylates (2). [5][6][7][8][9] We anticipated that if high reactivity and selectivity of the reactions using acrylamides arise not from their electron-deficient nature but high coordination ability, highly coordinative electron-rich enamides [10] would also be suitable cycloaddition partners toward 1,6-enynes.Herein, we disclose the cationic rhodium(I) complex catalyzed regio-, diastereo-, and enantioselective [2+ +2+ +2] cycloaddition of 1,6enynes (1)with enamides and vinyl carboxylates (2).…”