This perspective showcases our development of benzylic and allylic amine and alcohol derivatives as electrophiles for stereospecific, nickel-catalyzed cross-coupling reactions, as well as the prior art that inspired our efforts. The success of our effort has relied on the use of benzyl ammonium triflates as electrophiles for cross-couplings via C–N bond activation and benzylic and allylic carboxylates for cross-couplings via C–O bond activation. Our work, along with others’ exciting discoveries, has demonstrated the potential of stereospecific, nickel-catalyzed cross-couplings of alkyl electrophiles in asymmetric synthesis, and enables efficient generation of both tertiary and quaternary stereocenters.

A metal-free, Lewis acid-promoted intramolecular aminocyanation of alkenes was developed. B(C6F5)3 activates N-sulfonyl cyanamides, leading an formal cleavage of the N-CN bonds in conjunction with vicinal addition of sulfonamide and nitrile groups across an alkene. This method enables atom-economical access to indolines and tetrahydroquinolines in excellent yields, and provides a complementary strategy for regioselective alkene difunctionalizations with sulfonamide and nitrile groups. Labeling experiments with 13C suggest a fully intramolecular cyclization pattern due to lack of label scrambling in double crossover experiments. Catalysis with Lewis acid is realized and the reaction can be conducted under air.

A metal-free, Lewis acid promoted intramolecular aminocyanation of alkenes was developed. B(C 6 F 5 ) 3 activates N-sulfonyl cyanamides, thus leading to a formal cleavage of the NÀCN bonds in conjunction with vicinal addition of sulfonamide and nitrile groups across an alkene. This method enables atom-economical access to indolines and tetrahydroquinolines in excellent yields, and provides a complementary strategy for regioselective alkene difunctionalizations with sulfonamide and nitrile groups. Labeling experiments with 13 C suggest a fully intramolecular cyclization pattern due to the lack of label scrambling in double crossover experiments. Catalysis with Lewis acid is realized and the reaction can be conducted under air.

The drimentine family is a class of hybrid isoprenoids derived from actinomycete bacteria. Members of this family display weak antitumor and antibacterial activity. Herein we report our efforts toward the total synthesis of drimentine C using three distinct approaches incorporating palladium-catalyzed Figure 1. General scaffold of drimentines and structure of indotertine A.[a] Scheme 2. Synthesis of terpenoid fragment 9 and attempts at organolithium coupling.

Nickel-catalyzed, stereospecific cross-couplings via activation of secondary C–O bonds has been well developed in the past few years. Meanwhile, stereospecific cross-couplings of tertiary electrophiles have been rarely explored. Herein, we describe a nickel-catalyzed, ligand-free Suzuki-Miyaura vinylation, using easily prepared, highly enantioenriched tertiary benzylic carboxylates to install all-carbon quaternary stereocenters in high yields and ee’s. In addition to allowing stereospecific vinylation of these substrates for the first time, this method overcomes the longstanding requirement for a naphthyl group on the benzylic carboxylate<br>

Nickel-catalyzed, stereospecific cross-couplings via activation of secondary C–O bonds has been well developed in the past few years. Meanwhile, stereospecific cross-couplings of tertiary electrophiles have been rarely explored. Herein, we describe a nickel-catalyzed, ligand-free Suzuki-Miyaura vinylation, using easily prepared, highly enantioenriched tertiary benzylic carboxylates to install all-carbon quaternary stereocenters in high yields and ee’s. In addition to allowing stereospecific vinylation of these substrates for the first time, this method overcomes the longstanding requirement for a naphthyl group on the benzylic carboxylate<br>

Formation of quaternary stereocenters is an essential goal for organic chemistry due to these centers' presence in numerous drugs and their importance in biological activity. Transition metal catalysis offers a unique approach to this challenge, but previous attempts have been limited in either scope or enantiomeric enrichment. We are introducing a stereospecific Suzuki cross coupling of enantioenriched benzyl alcohol derivatives via C‐O bond activation that yields quaternary stereocenters with both aryl and vinyl substituents. Using benzylic carboxylates available in high enantiopurity, an air‐stable, inexpensive nickel source, and pinacol boronates, the reaction yields products in high yield and enantioenrichment and can tolerate a wide range of functional groups, including heteroaromatics. The optimization and scope of these reactions will be presented.Support or Funding InformationThe National Institutes of Health (R01 GM111820) is gratefully acknowledged.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Geminal substitution of the alkene is required for the reaction since the allyl substrate does not react.