Modular access to substituted cyclohexanes with kinetic stereocontrol

Abstract

Substituted six-membered cyclic hydrocarbons are common constituents of biologically active compounds. Although methods for the synthesis of thermodynamically favored, disubstituted cyclohexanes are well established, a reliable and modular protocol for the synthesis of their stereoisomers is still elusive. Herein, we report a general strategy for the modular synthesis of disubstituted cyclohexanes with excellent kinetic stereocontrol from readily accessible substituted methylenecyclohexanes by the implementation of chain-walking catalysis. Mechanistically, the initial introduction of a sterically demanding boron ester group adjacent to the cyclohexane is key to guiding the stereochemical outcome. The synthetic potential of this methodology has been highlighted in late-stage modification of complex bioactive molecules and in comparison with current cross-coupling techniques.

Recent progress in nickel-catalyzed carboboration of alkenes

“…Very recently, Yin and co-workers 40 developed a general strategy of chain-walking Ni-catalyzed 1,1-benzylboration of readily accessible substituted methylene cyclohexanes with benzyl chlorides and B 2 pin 2 to synthesize various disubstituted cyclohexanes with excellent kinetic stereocontrol (Scheme 33). This reaction had a wide substrate range and good functional group tolerance, including aryl bromide, ester, amine, amide, imide, and α,β-unsaturated ketone functionalities.…”

“…25 A broad range of olefins and aryl bromides could be tolerated well in this system to produce a diverse assortment of products. The synthesis of diarylquaternary carbons could be achieved with cyclic substrates including piperidinyl (36), tetrahydrofuran (37), benzocyclohexenyl (40) and so on. In addition, the acyclic substrates could also give the target products with diarylquaternary carbons in excellent yields.…”

“…Very recently, Yin and co-workers 40 developed a general strategy of chain-walking Ni-catalyzed 1,1-benzylboration of…”

Nickel-Catalyzed Regio- and Enantioselective Borylative Coupling of Terminal Alkenes with Alkyl Halides Enabled by an Anionic Bisoxazoline Ligand

“…As an extension of our interest in the catalytic alkene transformations, particularly after the success of asymmetric borylative coupling of terminal alkenes with sp 2 -carbon electrophiles, we turned our attention to more challenging sp 3 -carbon electrophiles. , The oxidative addition of sp 3 -carbon electrophiles is more difficult and probably requires new, structurally different ligands to modulate the multicomponent reaction chemoselectivity. Moreover, chain-walking can not only occur on the olefin part but also on the alkyl electrophile part.…”

Versatile electrooxidative amino- and oxyselenation of alkenes

“…Compared with the extensively studied difunctionalisation of activated alkenes, the conversion of inactive aliphatic olefins has rarely been researched and the general and green protocol for the difunctionalisation of activated alkenes [58][59][60][61][62][63] and challenging 1-aryl-1,3-dienes 64,65 is far from established. Based on our previous work on the electrooxidative trifunctionalisation of styrenes, 66 we herein present a universal methodology for the regioselective aminoselenation reaction of alkenes including activated arylalkenes, challenging 1-aryl-1,3dienes, and non-activated aliphatic alkenes, and excitingly the oxyselenation of inert alkenes was also successful from diversified carboxylic acids (Scheme 1).…”