Rhodium- or Copper-Catalysed CH-Insertion of Carbenoids into Dihydro­aromatic Compounds and Acyclic 1,4-Dienes

Abstract

A straightforward reaction sequence consisting of a cobalt-catalysed Diels-Alder reaction for the generation of dihydroaromatic compounds and a rhodium-or alternatively a coppercatalysed CH-insertion reaction of carbenoids from diazo esters generates highly substituted benzene derivatives. When acyclic 1,4-dienes are synthesised by a cobalt-catalysed 1,4-hydrovinylation reaction, the rhodium-catalysed conversion with diazo esters leads to cyclopropanation rather than CH-insertion products.The selective formation of carbon-carbon bonds using aryl-, alkenyl-and more recently alkyl halides by means of palladium or in general transition-metal catalysis is still of uttermost importance. 1 Additionally, the selective functionalisation of a carbon-hydrogen bond by insertion of a carbenoid has also proved to be a valuable method for the construction of more complex molecules. 2 Inspired by the work of Davies and Müller on the rhodium-catalysed CH-insertion reaction utilising 1,4-cyclohexadiene, 3 we started investigating further modifications of dihydroaromatic compounds which are easily accessible by our cobalt-catalysed Diels-Alder reaction of alkynes with 1,3-dienes. 4 Scheme 1The rhodium-catalysed carbon-carbon bond formation of diazo esters with 1,4-cyclohexadiene is reported to be performed with a large excess of the dihydroaromatic derivative. 3 A more economic process is therefore desirable to minimise the use of excess reagents. 5 Therefore, we performed a series of reactions on two different dihydroaromatic compounds 3a and 3b with two diazo ester derivatives 4a and 4b (Scheme 1) to optimise the reaction conditions. To determine the regiochemistry of the products a DDQ oxidation to 6 was performed directly after the CH-insertion reaction. Two dimensional NMR spectra revealed that the new carbon-carbon bond was formed exclusively at the less-hindered CH 2 group of the dihydroaromatic compounds 5. The results of these optimisations are given in Table 1.

Functionalization of Carbon–Hydrogen Bonds Through Transition Metal Carbenoid Insertion

“…In these cases, less than 5% of the cyclopropane was observed, and 53-64% yield of the C-H insertion product 88 was isolated in 91-95% ee. Davies [67,86], Doyle [87], and Hilt [88,89] have developed systems for selective C-H insertion into 1,4-cyclohexadiene derivatives (Fig. 7).…”

“…The ultimate fate of the diene differed in each case; in the indatraline synthesis it was ultimately oxidized to a benzene ring with DDQ, and in the preparation of cetiedil it was reduced to a cyclohexane with H 2 and Pd/C. Hilt took a slightly different approach toward the functionalization of cyclohexadienes [88,89]. He reasoned that subsequent DDQ oxidation of the insertion products would provide facile access to substituted benzene derivatives 101 that would be difficult to obtain by traditional means (Scheme 21).…”