Carbonylation

Abstract

Carbon monoxide, with the use of transition-metal catalysis, has become a valuable C1 building block. 1 Carbonylation is one method of intercepting the palladium intermediates generated by oxidative addition. 2 If the reaction is run under at atmosphere of carbon monoxide, then the palladium intermediate may undergo CO insertion, generating an 1 -acyl complex, before any other reagent (Scheme 4.1). Whether it will do so in useful quantities is a question of kinetics: will the rate of CO insertion be faster than the rates of the other possible processes? The reactivity of the other reagents may be reduced by careful choice of functionality, or their concentration may be reduced by slow addition, perhaps by use of a syringe pump. The rate of reactions involving carbon monoxide may be increased by the use of higher pressures. While many reactions proceed satisfactorily at atmospheric pressure, other reactions require increased pressures. Pressures up to 100 psi may be safely attained in good quality, heavy-wall glass vessels, fitted with a pressure head and safety release valve, and operated behind a safety shield. Much higher pressures may be achieved using steel autoclaves. * Carbonylative Coupling Reactions: Synthesis of Carbonyl DerivativesCan we intercept the acyl intermediate with a main-group organometallic, or other carbon nucleophile? This could be a useful synthesis of ketones (Scheme 4.2). 3 How would the mechanism work? It would require coordination and insertion of CO before reductive elimination (Scheme 4.3). As reductive elimination is usually fast, CO must be involved before transmetallation. Ketone production will be favoured over direct coupling if the rate of CO insertion is faster than the rate of transmetallation of L 2 PdR'X. We can make CO chemistry faster by increasing the pressure; we can make transmetallation slower by using a less-reactive organometallic, and also by slow addition, to get the right kinetics. Although slow transmetallation is favoured by the use of less electropositive metals, M, such as tin, boron and silicon, a wide range of organometallics have been employed too. In addition to tin (Schemes 4.4 and 4.5) 4,5 , boron (Scheme 4.6) 6 and silicon (Scheme 4.7), 7 examples include aluminium (Scheme 4.8) 8 and zinc (Scheme 4.9) 9 . * WARNING Carbon monoxide is highly toxic. All reactions using this gas should be carried out in an efficient fume cupboard. Reactions under pressure should be carried out behind additional safety shielding.