Chemoselective and diastereoselective tandem C-C, C-O, and C-N bond forming reactions

The formation of C–C bonds with simultaneous control over incipient stereochemistry is at the very heart of organic synthesis and at the forefront of chemical research. One of our approaches towards this end entails generation of functionalized 1,1-heterobimetallic intermediates, wherein each metal-carbon bond exhibits distinct reactivity that can be selectively exploited in C–C bond-forming reactions or functional group manipulations. The challenges in generation and reactions of such 1-alkenyl-1,1-bimetallics lies in controlling the double bond geometry, simplifying generation, and maximizing functional group tolerance. Our group recently reported a practical generation of 1,1-heterobimetallics from air-stable B(pin)-substituted alkynylboronate esters and demonstrated their utility in a variety of one-pot transformations to provide boronate substituted allylic alcohols, dienols, α-hydroxy ketones, and protected α,β-dihydroxy ketones with high diastereoselectivity. Taking into account the potential usefulness of 1-alkenyl-1,1-heterobimetallics in stereoselective organic synthesis, more applications of these reagents were explored in this doctoral thesis. Introduced in Chapter 1 is a practical application of 1-alkenyl-1,1-heterobimetallic intermediates in the synthesis of versatile cyclopropyl alcohol boronate esters, which are valuable building blocks. Thus, hydroboration of 1-alkynyl-1-boronate esters with dicyclohexylborane generates 1-alkenyl-1,1-diboro species. In Chapter 2, I outline a highly diastereoselective synthesis of B(pin)-substituted epoxy alcohols from readily available 2-B(pin)-substituted allylic alcohols. The success of this reaction methodology relics on chemoselective activation of the C=C towards peroxides in the presence of a vinyl B–C bond. Herein we report a method to divert the oxidation of vinyl boronate esters from the B–C bond to epoxidation of the C=C bond. Polyoxygenated hydrocarbons are ubiquitous structural elements in complex natural products and form the backbone of sugars. An important structural motif within this class is 2-keto-1,3-diols, which are present in numerous natural products and synthetic intermediates. In Chapter 3, we describe a novel stereoselective approach to the synthesis of 2-keto-anti-1,3-diols that involves a straightforward tandem oxidation of readily accessible 2-B(pin) allylic alcohols. In Chapter 4, I disclose new approaches to the syntheses of α-amino ketones, 1,4-dicarbonyl compounds, trisubstituted allylic amines, and trisubstituted allylic acetates and derivatives are disclosed. This chemistry is made possible by embedding a vinyl boronate ester within an allylic acetate. Synthesis of the requisite 2-B(pin) substituted allylic acetates are performed on gram scale in one-pot procedures using heterobimetallic reagents in 67–82% yield. In this chapter, I have shown that these compounds are excellent substrates for Pd-catalyzed allylic substitutions. (Abstract shortened by UMI.