Scott K. Bur

The Synthesis of Heterocycles Using Cascade Chemistry

Publisher Summary This chapter reviews the kind of reactions that have been sequenced into cascades to produce heterocyclic molecules. The fact that multiple reactions give rise to a cascade sequence makes the categorization of these processes difficult. From the selective sampling of cascade reactions for the synthesis of heterocyclic molecules that has been outlined in this chapter, it is clear that virtually any reaction can be incorporated into a tandem sequence. Many of these cascades rapidly construct hetero-polycyclic systems that are difficult to produce in other ways. Several cascade sequences for heterocyclic synthesis have been well explored: (1) Padwas rhodium carbene-initiated dipolar cycloadditions, (2) Denmarks nitroalkene [4+2]/[3+2]-cycloadditions, (3) Overmans Aza-Cope/Mannich cascade, (4) Bunces conjugate addition strategy, (5) Molinas Aza-Wittig/heterocumulene cyclization reactions, and (6) Griggs use of relays and switches in palladium-mediated cascades have matured into significant synthetic tools. Familiar multi-component reactions, such as the Ugi reaction, are being used in interesting ways. Other sequences show tremendous promise. Fus asymmetric Kinugasa reaction, indium-initiated radical cascades, Buchwalds copper catalyzed N-arylation reactions, Trosts alkyne heterocyclization, and Hoveyda and Schrock tandem AROM/RCM reactions all provide improvements in stereoselectivity and involve the use of environmentally benign reagents. Continued development of these cascade reactions will have a significant impact on the processes used to make heterocyclic compounds on an industrial scale.

1,3-Sulfur Shifts: Mechanism and Synthetic Utility

While allylic migrations are well known, 1,3-sulfur shifts are relatively rare. These shifts occur through a variety of mechanisms depending upon the substrate type and the reaction conditions. Radical-chain, ion-pair, dipolar, and symmetry-forbidden 1,3-sigmatropic mechanisms have all been proposed. Allylic sulfur shifts have been used in the synthesis of sulfides and sulfones of higher complexity, the stereospecific synthesis of alkenes, and the construction of ketones. This comprehensive survey of 1,3-sulfur migrations pays particular attention to the reported mechanisms and synthetic application.

Asymmetric reactions employing 1,3-dipoles

The preparation of heterocyclic compounds using 1,3-dipolar cycloaddition chemistry is now well recognized in the fields of organic synthesis, drug discovery efforts, polymer chemistry, and materials science. As highlighted in this review, a growing area of interest in organic synthesis involves the enantioselectivity aspects of dipolar cycloaddition chemistry for the preparation of many different classes of natural products. Asymmetric synthesis of natural products using chiral substrates has been elegantly accomplished over the past decade using an assortment of dipole intermediates and represents the focus of this review article.