Enantioselective cyanation via radical-mediated C\u2013C single bond cleavage for synthesis of chiral dinitriles

Tao Wang,Xi-Sheng Wang,Rui Wang,Yan-Lin Li,Yi-Ning Wang,Bo-Chao Zhang,Chi Yang

doi:10.1038/s41467-019-13369-x

Tao Wang, Xi-Sheng Wang + Show 5 more

Open Access

https://doi.org/10.1038/s41467-019-13369-x

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Abstract

Ring-opening reaction via selective cleavage of C–C bond is known as a powerful strategy for construction of complex molecules. Complementary to the ionic process focusing on mostly small ring systems, radical-mediated C–C bond cleavage offers a solution for further diverse enantioselective functionalization benefited from its mild conditions, whereas such asymmetric transformations are still limited to three-membered rings so far. Herein, we describe radical-mediated ring-opening and enantioselective cyanation of four- and five-membered cycloketone oxime esters to access chiral 1,5- and 1,6-dinitriles. Employment of dual photoredox/copper catalysis is essential for the asymmetric ring-opening cyanation of cyclopentanone oxime esters. Both reactions proceed under mild conditions giving chiral dinitriles in high yields and enantioselectivity with low catalyst loading and broad substrate scope. The products dinitriles can be converted to valuable optically active diamides and diamines. Mechanistic studies indicate that the benzylic radical generated via C–C single bond cleavage is involved in the catalytic cycle.

Highlights

Ring-opening reaction via selective cleavage of C–C bond is known as a powerful strategy for construction of complex molecules
It is worthy of note that C–C single bond cleavage and asymmetric radical cyanation of less strained 5-membered cycloketone oxime ester can be expediently achieved by merging photoredox catalysis with copper catalysis
Our studies commenced with cyclopentanone oxime ester 1a used as the pilot substrate, and trimethylsilyl cyanide (TMSCN) as the coupling partner in the presence of a catalytic amount of Cu (MeCN)4PF6 (10 mol%) at room temperature

Summary

Introduction

Ring-opening reaction via selective cleavage of C–C bond is known as a powerful strategy for construction of complex molecules. According to the pioneering discoveries of Zard[56,57] and recent works from other groups[58,59], iminyl radical-mediated ring-opening of cyclic oxime derivatives is an efficient pathway to cleave C–C single bond via β-scission As such transformation generates cyanoalkyl radical in situ, we envision this radical could be further trapped by chiral transitionmetal catalyst, followed by reductive elimination from the metal cyanide complex to furnish corresponding optically active dinitrile[60,61,62,63,64,65,66]. It is worthy of note that C–C single bond cleavage and asymmetric radical cyanation of less strained 5-membered cycloketone oxime ester can be expediently achieved by merging photoredox catalysis with copper catalysis Under mild conditions, both asymmetric transformations demonstrate high catalytic reactivity, excellent enantioselectivity, low catalyst loading and broad substrate scope. The key to success is the capture of the cyanoalkyl radical in situ generated via ring-opening C–C cleavage with chiral copper catalyst resulting in an enantioselective cyanation through stereoselective reductive elimination

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Conclusion