No abstract

Understanding how catalytic asymmetric reactions with racemic starting materials can operate would enable new enantioselective cross coupling reactions giving 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 13 C kinetic isotope effects provide quantitative information about the transition state structures of two key elementary steps in the catalytic cycle -transmetalation and oxidative addition. Experiments using configurationally stable, deuterium labelled substrates reveal oxidative addition can happen via syn-or antipathways which controls diastereoselectivity. DFT 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 understanding asymmetric Rh-allyl chemistry and enable the discovery and application of asymmetric reactions with racemic substrates.

A new strategy to access macrocyclic enynes was developed. To block undesired ene−yne cyclization pathways, alkynes were protected via bromination and the resultant acyclic vic-(E)-dibromotrienes participated in selective ene−ene ring closing metathesis reactions. Zinc-promoted deprotection of (E)-dibromodienes provided macrocyclic enynes in high yields.

Enantiomerically enriched allyl halides are rare due to their configurational lability. Stable piperidine-based allyl chloride enantiomers can be produced via kinetic resolution, and undergo highly enantiospecific catalyst-free substitutions.

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.T he transannular Diels−Alder (TADA) reaction is a potent synthetic tool for building complex organic scaffolds. 1TADA reactions are exploited in total syntheses due to their versatility, atom economy, and unique stereoselectivity.2 Studies on spinosyn A biosynthesis led to the discovery of the first pure Diels−Alderase enzyme that, in fact, catalyzes a transannular Diels−Alder transformation.3 Although TADA reactions have been widely investigated, utilization of transition metals to promote or catalyze such transformations remains poorly established. 4Cobalt−alkyne complexes are versatile species with myriad applications in synthetic chemistry. In addition to operating as protected alkynes 5 and stabilized propargyl cations, 6 dicobalt hexacarbonyl−alkyne complexes participate in several important cycloaddition reactions. 7 In particular, the [2 + 2 + 1] cycloaddition known as the Pauson−Khand reaction (PKR) is the most frequently studied. 8 However, studies on other cycloaddition reactions of alkyne−{Co 2 (CO) 6 } complexes, especially the [4 + 2] reaction, are scarce. The only reported examples of [4 + 2] cycloaddition reactions with alkyne− {Co 2 (CO) 6 } complexes are (1) intermolecular tandem Diels− Alder/Pauson−Khand reactions of a few terminal alkyne complexes with 1,3-cyclohexadiene 9 and (2) intermolecular Diels−Alder reactions with complexes of otherwise inaccessible strained and reactive cyclic alkynes.10 Despite this limited precedence, we postulated that [4 + 2] cycloaddition reactions of dicobalt complexes would make structures unattainable via metal-free Diels−Alder reactions accessible and that cobaltpromoted TADA reactions would present a unique entry to both organocobalt and macrocycle chemistry. Herein, we demonstrate the first transannular [4 + 2] cycloadditions of macrocyclic dienyne−{Co 2 (CO) 6 } complexes and the advantages over metal-free TADA reactions.We reported palladium(II)-catalyzed oxidative coupling of bis(vinylboronate esters) as a mild and facile entry to macrocyclic trienes and dienynes.11 This approach efficiently provided strained cyclic substrates, some of which, such as 2, readily underwent proximity-induced 12 TADA reactions at room temperature (Scheme 1). 13To explore TADA reactivity of 14-membered alkynes, we needed to synthesize dienyne 11 (Scheme 2). Trials to prepare triyne 9 via classical S N 2 reactions with various nucleophi...