Enantioselective Total Synthesis of (+)-Cassiol

An enantioselective total synthesis of (+)-cassiol is reported. The complex derived from Pd-2(pmdba)(3) and enantiopure t-BuPHOX ligand catalyzes enantioconvergent decarboxylative alkylation to generate the quaternary carbon stereocenter at an early stage. The overall synthetic strategy involves a convergent late-stage coupling of two fragments. The synthesis features a longest linear sequence of eight steps

Efficiency of the Wang-Landau algorithm: a simple test case

We analyze the efficiency of the Wang-Landau algorithm to sample a multimodal distribution on a prototypical simple test case. We show that the exit time from a metastable state is much smaller for the Wang Landau dynamics than for the original standard Metropolis-Hastings algorithm, in some asymptotic regime. Our results are confirmed by numerical experiments on a more realistic test case

Enantioselective Tsuji Allylations

The family of allylation reactions developed by Tsuji in the 1980s are capable of generating tertiary and quaternary carbon stereocenters from several synthetic precursors. Despite the utility of these transformations, they have seen little use in the synthesis of natural products. Recently, the power of these reactions was significantly enhanced by the development of enantioselective versions of these transformations. Applications of these methods to the enantioselective syntheses of natural products and pharmaceutical compounds highlight the importance of these developments

Pd-catalyzed enantioselective aerobic oxidation of secondary alcohols: Applications to the total synthesis of alkaloids

Enantioselective syntheses of the alkaloids (-)-aurantioclavine, (+)-amurensinine, (-)-lobeline, and (-)- and (+)-sedamine are described. The syntheses demonstrate the effectiveness of the Pd-catalyzed asymmetric oxidation of secondary alcohols in diverse contexts and the ability of this methodology to set the absolute configuration of multiple stereocenters in a single operation. The utility of an aryne C-C insertion reaction in accessing complex polycyclic frameworks is also described

Optimal importance sampling for overdamped Langevin dynamics

Calculating averages with respect to multimodal probability distributions is often necessary in applications. Markov chain Monte Carlo (MCMC) methods to this end, which are based on time averages along a realization of a Markov process ergodic with respect to the target probability distribution, are usually plagued by a large variance due to the metastability of the process. In this work, we mathematically analyze an importance sampling approach for MCMC methods that rely on the overdamped Langevin dynamics. Specifically, we study an estimator based on an ergodic average along a realization of an overdamped Langevin process for a modified potential. The estimator we consider incorporates a reweighting term in order to rectify the bias that would otherwise be introduced by this modification of the potential. We obtain an explicit expression in dimension 1 for the biasing potential that minimizes the asymptotic variance of the estimator for a given observable, and propose a general numerical approach for approximating the optimal potential in the multi-dimensional setting. We also investigate an alternative approach where, instead of the asymptotic variance for a given observable, a weighted average of the asymptotic variances corresponding to a class of observables is minimized. Finally, we demonstrate the capabilities of the proposed method by means of numerical experiments

Preparation of (S)-2-Allyl-2-methylcyclohexanone (Cyclohexanone, 2-methyl-2-(2-propen-1-yl)-, (2S)-)

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High-Throughput Screening of the Asymmetric Decarboxylative Alkylation Reaction of Enolate-Stabilized Enol Carbonates

The use of high-throughput screening allowed for the optimization of reaction conditions for the palladium-catalyzed asymmetric decarboxylative alkylation reaction of enolate-stabilized enol carbonates. Changing to a nonpolar reaction solvent and to an electron-deficient PHOX derivative as ligand from our standard ­reaction conditions improved the enantioselectivity for the alkylation of a ketal-protected,1,3-diketone-derived enol carbonate from 28% ee to 84% ee. Similar improvements in enantioselectivity were seen for a β-keto ester derived and an α-phenyl cyclohexanone-­derived enol carbonate

A reduced model for shock and detonation waves. II. The reactive case

We present a mesoscopic model for reactive shock waves, which extends a previous model proposed in [G. Stoltz, Europhys. Lett. 76 (2006), 849]. A complex molecule (or a group of molecules) is replaced by a single mesoparticle, evolving according to some Dissipative Particle Dynamics. Chemical reactions can be handled in a mean way by considering an additional variable per particle describing a rate of reaction. The evolution of this rate is governed by the kinetics of a reversible exothermic reaction. Numerical results give profiles in qualitative agreement with all-atom studies