Palladium‐Catalyzed Asymmetric [4+3] Cyclization of Trimethylenemethane: Regio‐, Diastereo‐, and Enantioselective Construction of Benzofuro[3,2‐b]azepine Skeletons

Abstract

The palladium‐catalyzed asymmetric [4+3] cyclization of trimethylenemethane donors with benzofuran‐derived azadienes furnishes chiral benzofuro[3,2‐b]azepine frameworks in high yields (up to 98 %) with exclusive regioselectivities and excellent stereoselectivities (up to >20:1 d.r., >99 % ee). This catalytic asymmetric [4+3] cyclization of Pd‐trimethylenemethane can enrich the arsenal of Pd‐TMM reactions in organic synthesis. In addition, this strategy provides an alternative approach to chiral azepines by a transition‐metal‐catalyzed asymmetric [4+3] cyclization.

Palladium-catalyzed [4 + 2] cycloaddition of amido-tethered allylic carbonates with oxazol-5-(4H)-ones: synthesis of piperidine-2,6-dione derivatives

“…As indicated in Table 3, we set R group as tertbutyl at first and tested the effect of Ar group on the reaction. These oxazol-5(4H)-ones whether having electron-donating or electron-withdrawing groups on the benzene ring of Ar group underwent the reaction well under the standard conditions to give the corresponding products in 55-96% yield (Table 3, entries [1][2][3][4][5][6][7][8][9][10][11]. An ortho group on the benzene ring had a certain negative impact on the reactivity in comparison with meta and para groups (Table 3, entries 7-9).…”

“…[1][2][3] In particular, an array of self-deprotonated or sequentially decarboxylated/deprotonated TMM precursors such as nitrile, trifluoromethyl, aldehyde, benzophenone imine, aza-aryl, and phospha-TMM have been utilized in [3 + n] cycloaddition reactions (Scheme 1a). [4][5][6][7] These types of Pd-TMM 1,3-carbodipoles generally produced five-membered rings with few exceptions. In further exploration, Pd-stabilized all carbon-1,4-dipoles were developed by using an additional carbon atom and were used to achieve [4 + n] cycloaddition reactions, forming a variety of cyclic structures (Scheme 1a).…”

Highly Regio‐, Diastereo‐, and Enantioselective Assembly of Azepino[2,3‐b]indoles viaPalladium‐Catalyzed [4 + 3] Cycloaddition†

“…However, in contrast to the well‐developed racemic versions, [ 5 ] catalytic asymmetric [4 + 3] cycloadditions for the preparation of chiral azepines are still rather limited. [ 6‐9 ] Very recently, Trost, [ 7 ] Shao, [ 8 ] and our group [ 9 ] independently reported palladium‐catalyzed asymmetric [4 + 3] cycloadditions of trimethylenemethanes (TMM) [ 10 ] with benzofuran‐derived azadienes, furnishing benzofuro[3,2‐ b ] azepine frameworks in excellent regio‐, diastereo‐, and enantioselectivities (Scheme 1a). Encouraged by this work, and in conjunction with our continuing efforts in the diversity‐oriented synthesis of chiral polycyclic indoles, [ 11 ] we envisaged that the highly reactive Pd‐TMM species could be trapped by indoline‐derived aza‐dienes via the enantioselective [4 + 3] cycloaddition process (Scheme 1b), which would provide a straightforward approach for the synthesis of biologically important chiral azepino[2,3‐ b ]indoles.…”

Stereoselective Synthesis of Acyclic Tetrasubstituted Alkenes from Anilines by Dearomatization and Trimethylenemethane Cycloaddition

“…12 We conceived that as outlined in Scheme 2, the dearomatized intermediate of the aniline could serve as acceptor which reacts with the nitrile-substituted TMM donor, generated from 2-(cyanomethyl)allyl carbonates upon oxidative addition with Pd 0 catalysis followed by deprotonation. 13 bond. Once this cycloaddition product is formed, aromatization to release the tension in the spiro structure and restore the aromaticity might be a considerable driving force helping to trigger a rearrangement.…”