Another method of introducing diversity is substitution at the carbon next to the nitrogen. This is archived by the Yamamoto rearrangement: Oxime mesylate 9 (see basic concepts) is reacted with an organometallic reagent (usually a Grignard reagent, but aluminium and cerium organic compounds were also employed) and the resulting imine (that rarely cound be isolated) is then either reduced with diisobutyl aluminium hydride (DIBAH) or reacted with allyl-Grignard to form a double substituted amine derivative.

Ten different alpha-substituted amines were synthesised by this method. Most of them showed high to very high antifungal potency. The two best substances of this series were 32 and 38 . Please note that 38 simulates the A-ring of the postulated HEI, which correspondes well with its excellent potency (see basic concepts and potencies).

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