Organocatalyzed asymmetric desymmetrization (ASD) reactions provide inexpensive and practical routes to introduce chirality into achiral feedstock (eq. 1). ASD is particularly important for the efficient preparation of chiral compounds in the pharmaceutical industry. In order to gain a better understanding of how these organocatalysts enable high enantioselectivity and efficiency, stable transition state analogues (TSAs) have been prepared which incorporate phosphonates to mimic the tetrahedral carbon of the transition state (Figure 1). Here the synthesis and characterization of TSA 1 and a precursor to TSA 2 which are prepared by Diels-Alder reactions are described. TSA 2 has been resolved into individual enantiomers in greater than 95% ee. Ultimately the TSA-catalyst interactions will be studied by two-dimensional NMR spectroscopy.

Syntheses of transition-state analogues for mechanistic studies of organocatalytic desymmetrization reactions

251st National Meeting (2016)

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