Reactive Dicarbon as a Flexible Ligand for Transition-Metal Coordination and Catalysis.

Dicarbon is a reactive carbon allotrope that naturally exists only in the high-temperature medium of stellar space. We report the successful preparation of a series of bottleable phosphine-stabilized dicarbon (PDC) molecules. We explore the use of these molecules as a new complementary class of carbene-like ligands featuring strong σ-donor (>NHCs and CAAcs) but weak π-acceptor properties. Steric map analysis of PDC based on Cavallo's SambVca program reveals comparable steric volume bulk of 32.5%, similar to the conventional IMes carbene. However, our PDCs exhibit dynamic steric flexibility modulated by the nature of the metal complexes and catalytic reaction environment. We demonstrate the catalytic utility of the PDC framework by its successful implementation for Suzuki-Miyaura cross-coupling and the reductive coupling reaction of an aldehyde and alkyne. Detailed investigations of the reductive coupling reaction reveal an important secondary interaction between PDC and metal complexes, which plays a critical role in the catalytic system.

Directing Group-Promoted Inert C-O Bond Activation Using Versatile Boronic Acid as a Coupling Agent.

A simple Ni(cod)2 and carbene mediated strategy facilitates the efficient catalytic cross-coupling of methoxyarenes with a variety of organoboron reagents. Directing groups facilitate the activation of inert C-O bonds in under-utilized aryl methyl ethers enabling their adaptation for C-C cross-coupling reactions as less toxic surrogates to the ubiquitous haloarenes. The method reported enables C-C cross-coupling with readily available and economical arylboronic acid reagents, which is unprecedented, and compares well with other organoboron reagents with similarly high reactivity. Extension to directing group assisted chemo-selective C-O bond cleavage, and further application towards the synthesis of novel bifunctionalized biaryls is reported. Key to the success of this protocol is the use of directing groups proximal to the reaction center to facilitate the activation of the inert C-OMe bond.

Formal syntheses of (-)-isoretronecanol, (+)-laburnine, and a concise enantioselective synthesis of (+)-turneforcidine.

The synthesis of functionalized pyroglutamates 15 and 16 could be achieved by the application of recently developed diastereodivergent asymmetric Michael addition reaction of iminoglycinate 7 to ethyl γ-silyloxycrotonate with >98:<2 diastereoselectivity followed by hydrolysis and lactamization. Formal syntheses of (-)-isoretronecanol and (+)-laburnine as well as a concise enantioselective synthesis of (+)-turneforcidine could be achieved from functionalized pyroglutamates 15 or 16.

Total Syntheses of (+)-α-Allokainic Acid and (-)-2- epi-α-Allokainic Acid Employing Ketopinic Amide as a Chiral Auxiliary.

Asymmetric Michael reaction of iminoglycinate 4 to α,ß-unsaturated esters had been developed with >98:<2 diastereoselectivity. A reverse of diastereoselectivity for Michael reaction could be achieved by the replacement of lithium enolate with magnesium enolate. This methodology was applied to the total syntheses of (+)-α-allokainic acid 1 and (-)-2- epi-α-allokainic acid 6 each in 11 synthetic steps starting from 4 in 17.8 and 18.0% yields, respectively.