Catalytic Enantioselective Construction of 6‐4 Ring‐Junction All‐Carbon Stereocenters and Mechanistic Insights

Abstract

Comprehensive Summary Developing reactions for the synthesis of 6‐6‐4 and 6‐4 carbocyclic scaffolds with a chiral quaternary center at the bridgehead position is highly desired, considering the existence of such skeletons in natural products with biological activities and the potential of using these molecules for downstream studies in chemical biology and medicinal chemistry. Report here is accessing these target skeletons with high chemo‐, regio‐ and enantio‐selectivities through Pd(II)/chiral N,N’‐disulfonyl bisimidazoline (Bim) ligand‐catalyzed asymmetric reaction of yne‐allenones and arylboronic acids. Realization of 6‐6‐4 skeleton with a ring‐junction all‐carbon stereocenter is a one‐step process while synthesizing 6‐4 skeleton is a two‐step process, which begins with intramolecular [2 + 2] reaction of allenes with alkynes, followed by Pd‐catalyzed asymmetric addition of arylboronic acids to cyclic enones generated in the first step. Noteworthy is that chiral Bim ligand as a C2‐symmetric N,N’‐bidentateanionic ligand, designed by us, in coordinating with Pd catalyst was first applied to catalyze asymmetric 1,4‐conjugate addition reaction with the high catalytic performance (the reaction can be carried out in air). DFT calculations have been applied to understand how these reactions take place, the origins of enantioselectivity, and relative reactivities of different substrates.

Lewis Acid-Catalyzed Remote Site-Selective Ring Deconstruction of Cyclobuteno[a]naphthalene-4-ones to Access Unsymmetric 1,1-Diarylated Olefins

“…X-ray crystallographic analysis was performed with a Siemens SMART CCD and a Siemens P4 diffractometer. Compounds 1 were prepared according to the reported procedures . All starting materials are known.…”

“…Compounds 1 were prepared according to the reported procedures. 16 All starting materials are known.…”

“…In recent years, our group has demonstrated the feasible application of in situ generated tricyclic cyclobutenes from intramolecular [2 + 2] cycloaddition of yne-allenones through selective cleavage of carbon–carbon bonds of four-membered ring . Very recently, we reported a Pd(II)/chiral N , N ′-disulfonyl bisimidazoline (Bim) ligand-catalyzed asymmetric reaction of yne-allenones and arylboronic acids, resulting in a series of cyclobuta[ a ]naphthalen-4(2 H )-ones with high enantioselectivity . Along this line, we reasoned that under suitable catalytic conditions, a highly strained four-membered ring that exists in these cyclobutenes could undergo a selective ring-opening process to access 1,1-diarylated olefins.…”

“…15 Very recently, we reported a Pd(II)/chiral N,N′disulfonyl bisimidazoline (Bim) ligand-catalyzed asymmetric reaction of yne-allenones and arylboronic acids, resulting in a series of cyclobuta[a]naphthalen-4(2H)-ones with high enantioselectivity. 16 Along this line, we reasoned that under suitable catalytic conditions, a highly strained four-membered ring that exists in these cyclobutenes could undergo a selective ring-opening process to access 1,1-diarylated olefins. Herein, we report our achievement in realizing this concept by carrying out a Sc(OTf) 3 -catalyzed remote site-selective ring deconstruction of racemic cyclobuteno[a]naphthalene-4-ones with various cheap and easily available alcohols, delivering a wide range of unsymmetric 1,1-diarylated olefins with broad substrate scope and good functional group tolerance (Scheme 1c).…”

Highlighting the Rich Chemistry of the Allenone Moiety

“…[74] Similarly, 1,4-conjugate addition of aryl boronic acids to alkynyl allenones 93 in the presence of palladium complexes has generated the corresponding compounds 95 c with good yields and exhibiting high functional group tolerance (Scheme 18c). [75] Also, the methodology has been extended to alkyl-tethered yne-allenones. Chiral ligand L6 designed by Jiang and collaborators has provided excellent enantiomeric excess up to 99% (Scheme 18c).…”