Synthesis of α-exo-Methylene-γ-butyrolactones: Recent Developments and Applications in Natural Product Synthesis

The α-exo-methylene-γ-butyrolactone moiety is present in a vast array of structurally diverse natural products and is often central to their biological activity. In this short review, we summarize new approaches to α-exo-methylene-γ-butyrolactones developed over the past decade as well as their applications in total synthesis.

1 Introduction

2 Approaches to α-exo-Methylene-γ-butyrolactones

2.1 Enantioselective Synthesis via Lactonization Approaches

2.2 Enantioselective Halolactonizations

2.3 Enantioselective Barbier-Type Allylation

2.4 C–H Insertion/Olefination Sequences

2.5 Alkene Cyclization

2.6 Strain-Driven Dyotropic Rearrangement

3 β-(Hydroxymethylalkyl)-α-exo-methylene-γ-butyrolactones

4 Applications in Total Synthesis

4.1 Sesquiterpene Lactones

4.2 Lignans

4.3 Other Monocyclic Natural Products

4.4 Choice of Methodology in Recent Total Syntheses

5 Summary and Outlook