Asymmetric aldol additions using chlorotitanium enolates of N-acyloxazolidinone, oxazolidinethione, and thiazolidinethione propionates proceed with high diastereoselectivity for the Evans or non-Evans syn product depending on the nature and amount of the base used. With 1 equiv of titanium tetrachloride and 2 equiv of (-)-sparteine as the base or 1 equiv of (-)-sparteine and 1 equiv of N-methyl-2-pyrrolidinone, selectivities of 97:3 to > 99:1 were obtained for the Evans syn aldol products using N-propionyl oxazolidinones, oxazolidinethiones, and thiazolidinethiones. The non-Evans syn aldol adducts are available with the oxazolidinethione and thiazolidinethiones by altering the Lewis acid/amine base ratios. The change in facial selectivity in the aldol additions is proposed to be a result of switching of mechanistic pathways between chelated and nonchelated transition states. The auxiliaries can be reductively removed or cleaved by nucleophilic acyl substitution. Iterative aldol sequences with high diastereoselectivity can also be accomplished.

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[reaction: see text] The diastereoselective alkylation of glycolate oxazolidinones has been demonstrated as a method for the enantioselective preparation of alpha-alkoxy carboxylic acid derivatives and selectively protected 1,2-diols. Various protecting groups on the glycolate hydroxyl and multiple substitution patterns on allylic iodides are tolerated in the alkylation. Yields for the alkylations are typically 70-85% with diastereoselectivities of >98:2.

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Organic Chemistry is a required course for programs in chemistry, biology, and many health science careers. It has historically been considered a highly challenging course with significant failure rates. As with many science disciplines, the teaching of Organic Chemistry has traditionally focused on unstructured exposition-centered delivery of course material. This report details efforts to transform the teaching of a large section of Organic Chemistry to a more student-centered approach through the use of a highly structured, active learning format. In this study, the authors examine student performance data on homogeneous examinations and course grades for two groups of students at a large public university for comparison between those that received highly structured active learning pedagogy and those that received traditional, unstructured, lecture pedagogy in Organic Chemistry. Data consist of repeated cross sections over 4 different years, with a total sample size n = 766. Regression and propensity score matching (PSM) are used to analyze student academic outcomes. Results suggest that students exposed to a highly structured, active learning pedagogy in Organic Chemistry scored statistically significantly higher on total points earned and final exam scores, and had a higher probability of an increase in their final course grade. Results further suggest that while increased structure in conjunction with active learning improved outcomes generally for all students who received it, those students at the lowest academic achievement levels experienced the most gains. This study is significant in its causal analysis of the impact of highly structured active learning on academic outcomes.

Covering: up to 2018With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets. A comprehensive compilation of historic to present-day cases as well as contemporary and future applications show that addressing the urgent need for a repository of publicly accessible raw NMR data has the potential to transform natural products (NPs) and associated fields of chemical and biomedical research. The call for advancing open sharing mechanisms for raw data is intended to enhance the transparency of experimental protocols, augment the reproducibility of reported outcomes, including biological studies, become a regular component of responsible research, and thereby enrich the integrity of NP research and related fields.

I m p r o v e d P r o c e d u r e f o r A s y m m e t r i c A lAbstract: Asymmetric aldol additions using chlorotitanium enolates of N-acyl oxazolidinones, oxazolidinethiones and thiazolidinethiones proceed with high diastereoselectivity for the 'Evans syn' product using one equivalent of titanium tetrachloride, one equivalent of diisopropylethylamine and one equivalent of N-methyl-2-pyrrolidinone. Typical selectivities of 94:6 to >98:2 were obtained using N-propionyl oxazolidinones, oxazolidinethiones and thiazolidinethiones at 0°C with stoichiometric amounts of aldehyde. Glycolate imides also gave high selectivities and high yields using this procedure.The chiral auxiliary mediated asymmetric aldol addition is one of the most general and widely used methods for asymmetric carbon-carbon bond formation. 1 The utility of the asymmetric aldol addition has been amply demonstrated through a multitude of synthetic applications. 2 The Evans protocol using dibutylboron enolates of acyl oxazolidinones is the most commonly utilized method providing the 'Evans syn' product as the major diastereomer. 3 Titanium(IV) 4-6 and tin(II) 7 enolates have also been shown to be effective in creating well-ordered transition states for aldol reactions. Evans and Yan have reported the use of chlorotitanium enolates of N-acyloxazolidinones in aldol additions, prepared by soft enolization using titanium tetrachloride and diisopropylethylamine amine. 4,6 However, slightly lower selectivity was observed than with the dibutylboron enolates and excess aldehyde (from 2-5 equiv) was required to achieve good levels of conversion. 4,6 We recently reported a protocol for accessing Evans syn aldol adducts using 1 equivalent of titanium tetrachloride and 2.2 equivalents of (-)-sparteine to form the titanium enolates of N-acyl oxazolidinethiones, thiazolidinethiones, and oxazolidinones. 8 Since it was proposed that the second equivalent of (-)-sparteine was functioning simply as a ligand for titanium, an improved protocol using 1 equivalent of titanium tetrachloride, 1 equivalent of (-)-sparteine and 1 equivalent of 1-methyl-2-pyrrolidinone (NMP), as the ligand for titanium, was investigated. 9 The improved TiCl 4 , (-)-sparteine-NMP, method was quite effective and has found increasingly wider use as an enolization method for asymmetric aldol reactions. 10 However, the need for the moderately expensive (-)-sparteine as the base has been the point of some concern with the method. Consequently, we recently reinvestigated the asymmetric aldol reaction with the goal of finding a set of conditions, which would obviate the need for (-)-sparteine as the base and perhaps offer improved performance in asymmetric aldol reactions of N-glycolyl oxazolidinones, oxazolidinethiones or thiazolidinethiones. We report here the results of our findings (Equation 1). Equation 1Diastereoselective aldol additions using TiCl 4 , (-)-sparteine, and NMP Our initial attempts to further improve conditions for the chlorotitanium enolate aldol reaction focused on finding a sui...

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