The Aldol-Tishchenko Reaction of Butanone, Cyclobutanone and a 3-Pentanone Derived Sulfinylimine and DFT Calculations of the Stereo-determining Step.

Herein, we present a highly diastereoselective method to furnish acyclic 3-amino-1,5-diol derivatives using a tandem double-aldol-Tishchenko protocol (dr up to >99 : 1) using a butanone derived sulfinylimine. In most cases only 1 diastereomer predominates, from a possible 16. The reaction is also regioselective. In addition, the highly challenging cyclobutanone and 3-pentanone derivatives are also amenable to a double-aldol-Tishchenko reaction, although the dr values are modest. Despite that, clean single diastereomers can be isolated, which should prove very useful in medicinal chemistry and other areas. Detailed DFT calculations support the observed stereoselectivities in all cases, providing a rationale for the excellent dr values in the butanone series and the moderate values for the 3-pentanone class.

Stereoselective Installation of Five Contiguous Stereogenic Centers in a Double Aldol-Tishchenko Cascade and Evaluation of the Key Transition State through DFT Calculation.

The stereoselective formation of 5 contiguous chiral centers in a single pot reaction is demonstrated using an aldol, aldol-Tishchenko reaction of N-tert-butyl sulfinimines. One diastereoisomer (from 32 possibilities) predominates, and a series of cyclic and acyclic 3-amino-1,5-diol derivatives are synthesized in good yields (up to 80%) and excellent diastereoselectivities (up to >98:2 dr). Investigations support two reversible aldol steps, and multiple intermediates which are funnelled through a remarkably selective, irreversible, Tishchenko reduction, in a Curtin-Hammett phenomenon. DFT calculations using a disolvated (THF) model reveal the factors controlling stereoselectivity in the final irreversible Tishchenko step.

Mechanism and Origins of Stereoselectivity of the Aldol-Tishchenko Reaction of Sulfinimines.

Density functional theory computations have elucidated the mechanism and origins of stereoselectivity in McGlacken's aldol-Tishchenko reaction for the diastereoselective synthesis of 1,3-amino alcohols using Ellman's t-butylsulfinimines as chiral auxiliaries. Variations of stereochemical outcome are dependent on the nature of the ketone starting materials used, and the aspects leading to these differences have been rationalized. The intramolecular hydride transfer step is the rate- and stereochemistry-determining step, and all prior steps are reversible.

Dialogue as skill: training a health professions workforce that can talk about race and racism.

Efforts in the field of multicultural education for the health professions have focused on increasing trainees' knowledge base and awareness of other cultures, and on teaching technical communication skills in cross-cultural encounters. Yet to be adequately addressed in training are profound issues of racial bias and the often awkward challenge of cross-racial dialogue, both of which likely play some part in well-documented racial disparities in health care encounters. We seek to establish the need for the skill of dialoguing explicitly with patients, colleagues, and others about race and racism and its implications for patient well-being, for clinical practice, and for the ongoing personal and professional development of health care professionals. We present evidence establishing the need to go beyond training in interview skills that efficiently "extract" relevant cultural and clinical information from patients. This evidence includes concepts from social psychology that include implicit bias, explicit bias, and aversive racism. Aiming to connect the dots of diverse literatures, we believe health professions educators and institutional leaders can play a pivotal role in reducing racial disparities in health care encounters by actively promoting, nurturing, and participating in this dialogue, modeling its value as an indispensable skill and institutional priority.

Self-reflection in multicultural training: be careful what you ask for.

Self-reflection in multicultural education is an important means to develop self-awareness and ultimately to change professional behavior in favor of more equitable health care to diverse populations. As conceptualized by scholars in the field of psychology, racial identity theory is critical to understanding and planning for the potentially wide range of predictable reactions to provocative activities, including those negative reactions that do not necessarily herald a flaw in programming. Careful consideration of racial identity developmental phases can also assist program planners to optimally meet the needs of individual physician trainees in their ongoing constructive professional and personal development, and in strategically mobilizing and having ready the type of institutional leadership that supports trainees' change processes. The authors focus on white physician trainees, the largest racial group of U.S. physicians and medical students. They first explain what they mean by the terms white and nonwhite. Racial identity theory is then applied, with true case examples, to explore such issues as where the self-proclaimed "color-blind" trainee fits into this theoretical schema, and how medical educators can best serve trainees who are resistant or indifferent to discussions of racism in medicine and equity in health care delivery. Ultimately, the authors' goal is to demonstrate that engendering genuine self-reflection can substantively improve the delivery of health care to the nation's diverse population. To help achieve that goal, they emphasize what to anticipate in effecting optimal trainee education and how to create an institutional climate supportive of individual change.