The synthesis of complex molecules relies on methods for the formation of carbon–carbon bonds. Methods that allow more than one carbon–carbon bond to be formed in a single step improve the efficiency of the process. The reaction of organometallic reagents with carbonyl compounds is one of the most popular methods of carbon–carbon bond formation. Adding two different groups to one carbonyl group, however, usually requires a cycle of reductive addition, followed by oxidation and then a second addition.

Now, Pei-Qiang Huang and co-workers from Xiamen University in China have developed1 a sequential addition of two different organometallic reagents to an amide or a lactam to produce a tertiary alkyl amine in a single pot. The carbonyl oxygen of the amide or lactam is first activated by formation of a triflate, which is a good leaving group. The iminium triflate thus formed is reacted with a Grignard reagent. The loss of the triflate group then results in a new iminium species that can react with a further organometallic reagent — and, importantly, this can be a different one from the first — to form the product.

A wide variety of different organometallic reagents can be employed for the second addition, including further Grignard reagents, alkynyl lithium reagents and even lithium enolates. Huang and co-workers also demonstrate that for a reaction with a lactam that already bears another substituent, the second addition can be made in a diastereoselective fashion.