Expanding the organocatalyzed α-chlorination-aldol reaction

Organocatalysis, while still a relatively new field in organic chemistry, now plays an indispensable role in organic synthesis. Transformations not accessible by classical synthetic methods are now not only routine, but mild, high yielding and increasingly sophisticated in what they can achieve. One such reaction is the α-chlorination-aldol reaction developed by the Britton group in 2013. This reaction has been demonstrated to provide access to stereochemically rich chlorohydrins from readily available and achiral starting materials. The reaction has found extensive utility in the concise synthesis of imino-cyclitols and carbohydrate analogues. In this thesis a more general approach to the tandem α-chlorination-aldol with different electrophiles or ketones is investigated. Within, we show that azodicarboxylates can be used as electrophiles to functionalize aldehydes prior to submission to an aldol reaction. These aminated aldol adducts are further investigated for their utility in synthesizing imino-cyclitols, and their ability to form cyclic, polyhydroxylated hydrazones. As well, new substrates are investigated for their propensity to engage in an α-chlorination-aldol reaction. Four new substrates are demonstrated to form the corresponding chlorinated aldol adducts in moderate yields and high enantioselectivity. Furthermore, we demonstrate that these new aldol adducts can provide access to novel, natural product-like scaffolds.