Mechanistic investigation of Rh(i)-catalysed asymmetric Suzuki–Miyaura coupling with racemic allyl halides

Understanding how catalytic asymmetric reactions with racemic starting materials can operate would enable new enantioselective cross-coupling reactions that give chiral products. Here we propose a catalytic cycle for the highly enantioselective Rh(I)-catalysed Suzuki–Miyaura coupling of boronic acids and racemic allyl halides. Natural abundance 13C kinetic isotope effects provide quantitative information about the transition-state structures of two key elementary steps in the catalytic cycle, transmetallation and oxidative addition. Experiments with configurationally stable, deuterium-labelled substrates revealed that oxidative addition can happen via syn- or anti-pathways, which control diastereoselectivity. Density functional theory calculations attribute the extremely high enantioselectivity to reductive elimination from a common Rh complex formed from both allyl halide enantiomers. Our conclusions are supported by analysis of the reaction kinetics. These insights into the sequence of bond-forming steps and their transition-state structures will contribute to our understanding of asymmetric Rh–allyl chemistry and enable the discovery and application of asymmetric reactions with racemic substrates

Transition Metal-Mediated Synthesis and Functionalization of Macrocycles

Transition metal-mediated synthesis and functionalization of macrocycles were investigated. A novel synthetic strategy was discovered to build macrocyclic enynes; vic-dibromo tetrasubstituted alkenes were utilized as highly effective protected alkyne groups in selective ene-ene ring closing metathesis reactions of (E)-dibromotrienes. Macrocyclic enynes with varied sizes and functionality were synthesized in excellent yields by facile Zn-promoted deprotection of (E)-dibromodiene rings. The new strategy circumvented high catalyst loadings and reaction condition restrictions; thus, was proven superior to traditional alkyne protection methods employing dicobalt octacarbonyl complexations. Cyclic enynes were obtained in a more step-economic and efficient manner compared to classical SN2 ring closing processes. The reactivity and utility of enyne rings were showcased by platinum(II)-catalyzed transannular cyclopropanations. The first dicobalt hexacarbonyl-promoted transannular [4+2] cycloaddition reactions were demonstrated. Optimized cycloadditions for macrocyclic dicobalt-dienyne complexes afforded target tricyclic scaffolds in a more effective manner than thermal transannular Diels-Alder reactions of metal-free dienyne rings. Further, dicobalt hexacarbonyl complexes of unactivated dienophiles underwent intermolecular room temperature-[4+2] cycloadditions with unactivated dienes leading to products that are inaccessible by thermal Diels-Alder reactions. Cycloaddition reactions of complexes were highly selective; [4+2] reaction adducts were obtained stereospecifically and competing Pauson-Khand reactions were not detected. Functionalizations of enyne macrocycles through intermolecular and transannular reactions of their corresponding dicobalt complexes were studied. Novel complex polycycles were prepared by intramolecular and intermolecular [2+2+2], [2+2+1+1], [2+2+1] cycloadditions. The chemoselectivity of dicobalt-promoted cycloadditions was altered by varying the promoter and solvents utilized. The first transannular Pauson-Khand reaction was discovered. The novel synthetic method was optimized and structural requirements for reaction substrates were investigated

Transannular [4 + 2] Cycloaddition Reactions of Cobalt-Complexed Macrocyclic Dienynes.

The first transannular [4 + 2] cycloaddition reactions of macrocyclic dicobalt hexacarbonyl-dienyne complexes were demonstrated. Complexes were conveniently prepared through palladium(II)-catalyzed intramolecular oxidative cyclization of bis(vinylboronate esters) followed by complexation with dicobalt octacarbonyl. Transannular [4 + 2] cycloaddition reactions of the complexes occurred at lower temperatures and shorter times than transannular Diels-Alder reactions of metal-free dienynes. Intermolecular control reactions confirmed the effect of cobalt complexation on [4 + 2] cycloaddition reactions of unactivated alkynes and dienes

Enantiomerically Enriched Tetrahydropyridine Allyl Chlorides

Enantiomerically enriched allyl halides are rare due to their configurational lability. Here we report stable piperidine-based allyl chloride enantiomers. These allyl chlorides can be produced via resolution, and undergo highly enantiospecific catalyst-free substitution reactions with C, N, O and S-based nucleophiles. Deuterium-labelled chloro-tetrahydropyridine, selectively prepared using the H/D primary kinetic isotope effect, and DFT calculations were used to investigate the mechanisms of the reactions. The allyl chlorides may also serve as valuable mechanistic tools for probing stereoselective reaction pathways