This account examines double asymmetric induction from theoretical and practical viewpoints. In the context of four major organic reactions-the aldol, Diels-Alder, catalytic hydrogenation, and epoxidation-it is shown that a double asymmetric induction can be analyzed in terms of the single asymmetric reactions of each of the two chiral reactants. A rule which qualitatively relates the results of these single asymmetric reactions with the outcome of the double asymmetric reaction is proposed. A powerful new strategy based on this rule for the predictable creation of new chiral centers is discussed and the use of this strategy for the synthesis of sugars and macrolides is presented.

Double Asymmetric Synthesis and a New Strategy for Stereochemical Control in Organic Synthesis

The use of photochemical transformations is a powerful strategy that allows for the formation of a high degree of molecular complexity from relatively simple building blocks in a single step. A central feature of all light-promoted transformations is the involvement of electronically excited states, generated upon absorption of photons. This produces transient reactive intermediates and significantly alters the reactivity of a chemical compound. The input of energy provided by light thus offers a means to produce strained and unique target compounds that cannot be assembled using thermal protocols. This review aims at highlighting photochemical transformations as a tool for rapidly accessing structurally and stereochemically diverse scaffolds. Synthetic designs based on photochemical transformations have the potential to afford complex polycyclic carbon skeletons with impressive efficiency, which are of high value in total synthesis.

Photochemical Approaches to Complex Chemotypes: Applications in Natural Product Synthesis

Photochemical reactions contribute in a significant way to the existing repertoire of carbon-carbon bond-forming reactions by allowing access to exceptional molecular structures that cannot be obtained by conventional means. In this Review, the most important photochemical transformations that have been employed in natural product synthesis are presented. Selected total syntheses are discussed as examples, with particular attention given to the photochemical key step and its stereoselectivity. The structural relationship between the photochemically generated molecule and the natural product is shown, and, where necessary, the consecutive reactions in the synthesis are illustrated and classified.

Photochemical reactions as key steps in natural product synthesis

Camphor derivatives as chiral auxiliaries in asymmetric synthesis

Synthesis of optically active pheromones

Using readily accessible 10-sulfonamido-isoborneols as regenerable, chiral auxiliaries, highly face-selective C–C-bond formations at Cα and Cβ of carboxylates could be conveniently achieved. Thus, conjugated additions of RCu to enoates (12) furnished, after saponification, β-substituted carboxylic acids 3 in 94–98% e.e. Similarly, propionates 12 yielded after deprotonation, enolate alkylation, and reductive ester cleavage the (R)-alcohols 15 in 78–98% e.e. The acid (+)-3e was converted to the pheromone (–)-11.

Camphorsulfonamide-Shielded, Asymmetric 1,4-Additions and Enolate Alkylations; Synthesis of a Southern Corn Rootworm Pheromone. Preliminary Communication

A new and efficient total synthesis of (.+-.)-longifolene

High asymmetric induction in diels-alder additions of cyclopentadiene to acrylates derived from isoborneol

Starting from 2-cyclopentenoyl chloride ((RS)- or (S)-8), the racemic as well as the enantiomerically pure (+)-sesquiterpenes longifolene ((±)- and (+)-1, resp.) and sativene ((±)- and (+)-2, resp.) were synthesized efficiently by a sequence of nine and ten steps, respectively. The key sequence 10 16 3 is the first strategic application of an intramolecular photoaddition/retro-aldolization sequence (intramolecular de Mayo reaction) in organic synthesis.

Syntheses of (±)‐ and Enantiomerically Pure (+)‐Longifolene and of (±)‐ and Enantiomerically Pure (+)‐Sativene by an Intramolecular de Mayo Reaction

Syntheses of (.+-.)- and enantiomerically pure (+)-longifolene and of (.+-.)- and enantiomerically pure (+)-sativene by an intramolecular de mayo reaction

Thierry Godel

Papers

Camphorsulfonamide-Shielded, Asymmetric 1,4-Additions and Enolate Alkylations; Synthesis of a Southern Corn Rootworm Pheromone. Preliminary Communication

A new and efficient total synthesis of (.+-.)-longifolene

High asymmetric induction in diels-alder additions of cyclopentadiene to acrylates derived from isoborneol

Syntheses of (±)‐ and Enantiomerically Pure (+)‐Longifolene and of (±)‐ and Enantiomerically Pure (+)‐Sativene by an Intramolecular de Mayo Reaction

Syntheses of (.+-.)- and enantiomerically pure (+)-longifolene and of (.+-.)- and enantiomerically pure (+)-sativene by an intramolecular de mayo reaction