In this chapter, the various methods of converting a carbonyl derivative to an alkene are discussed. Particular focus has been given to recently developed methods and their use in the context of natural product synthesis. Formally this volume in the series is devoted to nonstabilized carbanion additions, but this mechanistic definition has not been strictly adhered to in this chapter. The methods are categorized according to the type of alkene synthesized, and the stabilizing group attached to the anion or carbene. In addition, all of the methods discussed involve the addition of a carbon unit to the carbonyl, followed by some type of elimination or cleavage to the alkene. To further narrow the scope of this chapter, the added carbon unit and the original carbonyl carbon must form the units of the alkene, as shown in Scheme 1. Aldehydes, ketones, esters and lactones, and amides and lactams are all featured in these sections, depending on the synthetic method being discussed.

3.1 – Alkene Synthesis

A ketal-tethered RCM strategy toward the synthesis of spiroketal related natural products

Total syntheses of ent-5-epi-montecristin
(1a) and of (−)-montecristin (1b) were accomplished.
The stereocenters of compounds 1a and 1b were established
by asymmetric dihydroxylations of the trans-configurated β,γ-unsaturated
esters 6 ( →
4, up to 80% ee; Scheme 3; improved
procedure with up to 94% ee: Scheme 7) and 56 ( →

55, 97% ee: Scheme 9) while the stereogenic CC bonds
stem from the carbocuprations 48
→
49 and 50
→

51 (Scheme 9). Treating hydroxylactones 27 (Scheme 7), 
3a (Scheme 12) and 3b (Scheme 13) with PPh3 and DEAD,
we found a racemization-free dehydration giving butenolide 26 and
epimerization-free dehydrations giving butenolides 2a and 2b
. Relating the [α]D values of synthetic 
1a and 1b to the [α]D value
of natural (+)-montecristin, the absolute configuration of its side-chain
stereocenters was determined to be R.

Elucidation of the stereostructure of the annonaceous acetogenin (+)-montecristin through total synthesis

The various methods for the de novo asymmetric synthesis of the pyranose sugars are surveyed. The presentation begins with the work of Masamune and Sharpless with the use of the Sharpless asymmetric epoxidation for the synthesis of all eight l-hexoses. The development of other asymmetric reactions and their application for the synthesis of specific hexopyranoses are further discussed. The broad application of the Achmatowicz rearrangement with asymmetric catalysis, for the synthesis of various pyranones and imino sugars, is also presented. Finally, the use of a diastereoselective palladium-catalyzed glycosylation with the Achmatowicz approach for the synthesis of oligosaccharides and applications to medicinal chemistry are discussed.

Derek W. Clissold

Papers

Synthesis of leukotriene A4 methyl ester from D-glucose