Lewis base activation of lewis acids. Addition of silyl ketene acetals to aldehydes

The weak Lewis acid silicon tetrachloride can be activated by catalytic amounts of the chiral bisphosphoramide (R,R)-3 to form a highly reactive, chiral trichlorosilyl cation which is an extremely effective promoter of aldol addition reactions between aldehydes and silyl ketene acetals. The tert-butyldimethylsilyl ketene acetal of methyl acetate adds nearly instantaneously to aromatic and olefinic aldehydes as well as aliphatic aldehydes (albeit more slowly) with excellent enantioselectivity. The homologous tert-butyldimethylsilyl ketene acetal of tert-butyl propanoate adds with nearly exclusive anti diastereoselectivity to a similar range of aldehydes also with excellent enantioselectivity. The origin of the slower reaction rate with aliphatic aldehydes is revealed to be the formation of chlorosilyl ether adducts.     

Lewis Base Catalysis of the Mukaiyama Directed Aldol Reaction: 40 Years of Inspiration and Advances

Since the landmark publications of the first directed aldol addition reaction in 1973, the site, diastereo‐, and enantioselective aldol reaction has been elevated to the rarefied status of being both a named and a strategy‐level reaction (the Mukaiyama directed aldol reaction). The importance of this reaction in the stereoselective synthesis of untold numbers of organic compounds, both natural and unnatural, cannot be overstated. However, its impact on the field extends beyond the impressive applications in synthesis. The directed aldol reaction has served as a fertile proving ground for new concepts and new methods for stereocontrol and catalysis. This Minireview provides a case history of how the challenges of merging site selectivity, diastereoselectivity, enantioselectivity, and catalysis into a unified reaction manifold stimulated the development of Lewis base catalyzed aldol addition reactions. The evolution of this process is chronicled from the authors’ laboratories as well as in those of Professor Teruaki Mukaiyama.     

Scalable Synthesis of the Potent HIV Inhibitor BMS‐986001 by Non‐Enzymatic Dynamic Kinetic Asymmetric Transformation (DYKAT)

Described herein is the synthesis of BMS‐986001 by employing two novel organocatalytic transformations: 1) a highly selective pyranose to furanose ring tautomerization to access an advanced intermediate, and 2) an unprecedented small‐molecule‐mediated dynamic kinetic resolution to access a variety of enantiopure pyranones, one of which served as a versatile building block for the multigram, stereoselective, and chromatography‐free synthesis of BMS‐986001. The synthesis required five chemical transformations and resulted in a 44 % overall yield.     

A modified functional delta method and its application to the estimation of risk functionals

The classical functional delta method (FDM) provides a convenient tool for deriving the asymptotic distribution of statistical functionals from the weak convergence of the respective empirical processes. However, for many interesting functionals depending on the tails of the underlying distribution this FDM cannot be applied since the method typically relies on Hadamard differentiability w.r.t. the uniform sup-norm. In this article, we present a version of the FDM which is suitable also for nonuniform sup-norms, with the outcome that the range of application of the FDM enlarges essentially. On one hand, our FDM, which we shall call the modified FDM, works for functionals that are “differentiable” in a weaker sense than Hadamard differentiability. On the other hand, it requires weak convergence of the empirical process w.r.t. a nonuniform sup-norm. The latter is not problematic since there exist strong respective results on weighted empirical processes obtained by Shorack and Wellner (1986) [25], Shao and Yu (1996) [23], Wu (2008) [32], and others. We illustrate the gain of the modified FDM by deriving the asymptotic distribution of plug-in estimates of popular risk measures that cannot be treated with the classical FDM.     

Rhenium-catalyzed 1,3-isomerization of allylic alcohols: scope and chirality transfer

The scope of the triphenylsilyl perrhennate (O3ReOSiPh3, 1) catalyzed 1,3-isomerization of allylic alcohols has been thoroughly explored. It was found to be effective for a wide variety of secondary and tertiary allylic alcohol substrates bearing aryl, alkyl, and cyano substituents. Two general reaction types were found which gave high levels of product selectivity: those driven by formation of an extended conjugated system and those driven by selective silylation of a particular isomer. The efficiency of chirality transfer with various substrates was investigated, and conditions were found in which secondary and tertiary allylic alcohols could be formed with high levels of enantioselectivity. Consideration of selectivity trends with respect to the nature of the substituents around the allylic system revealed that this is a reliable and predictable method for allylic alcohol synthesis.     

Effect of energy addition on MR $\rightarrow$ RR transition

A combined computational and experimental study was performed to investigate the effect of a single laser energy pulse on the transition from a Mach Reflection (MR) to a Regular Reflection (RR) in the Dual Solution Domain (DSD). The freestream Mach number is 3.45 and two oblique shock waves are formed by two symmetric wedges. These conditions correspond to a point midway within the DSD wherein either an MR or an RR is possible. A steady MR was first obtained experimentally and numerically, then a single laser pulse was deposited above the horizontal center plane. In the experiment, the laser beam was focused resulting in a deposition volume of approximately 3 mm³, while in the simulation, the laser pulse was modeled as an initial variation of the temperature and pressure using Gaussian profile. A grid refinement study was conducted to assess the accuracy of the numerical simulations. For the steady MR, the simulation showed the variation of Mach stem height along the span due to side effects. The predicted spanwise averaged Mach stem height was 1.96 mm within 2% of the experimental value of 2 mm. The experiment showed that the Mach stem height decreased to 30% of its original height due to the interaction with the thermal spot generated by the laser pulse and then returned to its original height by s. That the Mach stem returned to its original height was most likely due to freestream turbulence in the wind tunnel. The numerical simulation successfully predicted the reverse transition from a stable MR to a stable RR and the stable RR persisted across the span. This study showed the capability of a laser energy pulse to control the reverse transition of MR RR within the Dual Solution Domain.     

Nonparametric inference for sequential <Emphasis Type="Italic">k</Emphasis>-out-of-<Emphasis Type="Italic">n</Emphasis> systems

The k-out-of-n model is commonly used in reliability theory. In this model the failure of any component of the system does not influence the components still at work. Sequential k-out-of-n systems have been introduced as an extension of k-out-of-n systems where the failure of some component of the system may influence the remaining ones. We consider nonparametric estimation of the cumulative hazard function, the reliability function and the quantile function of sequential k-out-of-n systems. Furthermore, nonparametric hypothesis testing for sequential k-out-of-n-systems is examined. We make use of counting processes to show strong consistency and weak convergence of the estimators and to derive the asymptotic distribution of the test statistics.