Development of the [3+2] annulation reactions of allylic silanes and their applications in natural products synthesis

The [3+2] annulation reactions of allylic silanes are powerful methods for the stereoselective preparation of functionalized five-membered carbocycles and heterocycles. This dissertation focuses on the development of the annulation reactions and their applications in the total syntheses of natural products. A review of allylsilane annulations and related chemistry is presented in Chapter 1. Chapter 2 describes the development of a new silyl group, the benzhydryldimethylsilyl group, for the [3+2] annulations of allylic silanes. A new stereoselective synthesis of γ-butyrolactones by the [3+2] annulation of allylic silanes with N-chlorosulfonyl isocyanate is described in Chapter 3. A concise enantioselective total synthesis of a γ-butyrolactone natural product (+)-blastmycinone using this reaction as the key step is also presented in this Chapter. Chapter 4 describes the total syntheses of a densely functionalized tetrahydrofuran natural product (±)-citreoviral and its 5-epimer. The key annulation reaction constructs the four contiguous stereocenters, including two tetrasubstituted stereocenters, of the natural product in a single step. That the [3+2] annulations of allylic silanes can achieve acyclic stereocontrol is demonstrated in Chapter 5. A convergent total synthesis of (9S)-dihydroerythronolide A has been accomplished using this methodology. The key annulation reaction serves to establish most of the stereochemistry of the target, including the two tetrasubstituted carbon stereocenters. In this chapter, the first efficient kinetic resolution of allylic silanes using an asymmetric [3+2] annulation and an unprecedented complex chelation-controlled aldol reaction of an α-hydroxyl ethyl ketone are also described.