Curiosity and simplicity in the invention and discovery of new metal-mediated reactions for organic synthesis*

Two organometallic themes of current interest are presented. The scope and generality of the reductive deoxygenation of carbonyl compounds to organozinc carbenoids using zinc in combination with a silicon electrophile is discussed. Alkoxycyclopropanation can be achieved using orthoformates as substrates. Preliminary observations on the development of a rhodium-catalyzed tandem hydrosilylation–intramolecular aldol sequence are discussed. The unparalleled power of metal-mediated reactions, either as stoichiometric reagents or as catalysts has, without question, revolutionized the art of organic synthesis, as witnessed by the ever-increasing armory of powerful but mild chemoselective and stereoand enantiospecific transformations that have been placed at the disposal of the skilled practitioner. Within this framework of organometallic synthesis alone, it is now perfectly possible for the specialist to devote his/her entire career to the discovery of new and useful reactions based even on the use of a single metal. When viewed from this perspective, and given that metal-based reactions form only one facet of our own research activities, we must accordingly be considered amateurs rather than professional organometallic chemists. The joy and vicarious pleasure of the amateur, however, is of course that he is permitted to indulge his curiosity by ranging over the periodic table as shown in Scheme 1 by some of our own adventures in recent years. *Lecture presented at the 11th IUPAC International Symposium on Organometallic Chemistry Directed Towards Organic Synthesis (OMCOS-11), Taipei, Taiwan, 22–26 July 2001. Other presentations are presented in this issue, pp. 1–186. Scheme 1 For the purpose of the present paper, however, two organometallic themes from our current research program have been selected for discussion. The first of these, and of long-term interest in our group [5], is concerned with the generation and reactivity of functionalized organozinc carbenoids [6] from carbonyl compounds, as encapsulated in Scheme 2, which views the growth of the organozinc carbenoid as resulting from a series of single-electron transfer steps from the zinc surface. From a mechanistic standpoint, the reaction sequence therefore bears a close resemblance to the Clemmensen reduction, except that the proton is replaced by a highly oxophilic silicon electrophile, which presumably provides a strong thermodynamic driving force with the formation of hexamethyldisiloxane or the related cyclic congener which may be produced when the entropically favored bis silicon electrophile, 1,2-bis(chlorodimethylsilyl) ethane is used. The advantage and inherent simplicity of such an approach is not only that it avoids the use of dangerous and/or toxic gem dihalo and diazo precursors, but also that the carbonyl group and its related congeners have always been considered as cornerstone building blocks for organic synthesis. The subsequent reactivity of the resultant organozinc carbenoids is of course determined by the structure of the carbonyl compound that was selected for study. Thus, as shown in Scheme 3, for a series of cyclic ketones, insertion into the neighboring C–H bond is the predominant reaction for 6-membered rings, thereby providing a direct and useful chemoand regioselective method for alkene formation [7]. The formation of bicyclo [3,3,0] octane from cyclooctanone by transannular insertion is also representative of carbenoid reactivity. By way of contrast, the selection of either an aromatic aldehyde or certain enones as substrates led to the discovery of the unusual symmetrical dicarbonyl coupling reaction [8] shown in Scheme 4. W. B. MOTHERWELL © 2002 IUPAC, Pure and Applied Chemistry 74, 135–142 136