Science of Synthesis

MacMillan, D. W. C.; Beeson, T. D., Science of Synthesis: Asymmetric Organocatalysis, (2012) 1, 300.

The α-oxyamination of aldehydes with 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) has been proposed to undergo a SOMO-catalysis mechanism in which substoichiometric amounts of iron(III) chloride oxidant are replenished by sodium nitrite and molecular oxygen.[‌25‌] Notably, the reaction can be catalyzed by first-generation imidazolidinone catalyst ‌28‌[‌54‌] or l-proline (albeit racemically), two catalysts that have not been demonstrated in other SOMO-catalysis reactions. Recent mechanistic studies indicate that the reaction may in fact proceed through a two-electron enamine catalysis pathway after iron complexation to 2,2,6,6-tetramethylpiperidin-1-oxyl to generate an electrophilic oxygen species (‌Scheme 29‌).[‌55‌] Cyclic voltammetry experiments indicate iron(III) chloride has insufficient oxidative potential to oxidize the enamine to the reactive radical cation ‌2‌ (see ‌Scheme 4‌) in dimethylformamide due to disproportionation, although iron(III) ferrocenium salts, which do not disproportionate in dimethylformamide, have a higher oxidative potential than iron(III) chloride in dimethylformamide and may ultimately be able to induce a SOMO pathway. This observation is supported by isomerization studies of a cis-cyclopropane-substituted aldehyde in which reactions performed with iron(III) chloride in dimethylformamide predominantly do not undergo cyclopropane isomerization, but those performed with iron(III) ferrocenium salts readily isomerize to give the trans-product trans-‌27‌ (‌Scheme 30‌).

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‌Meeeeeeeeee 88‌

M8	MMMMM (eeeee)	ee (%)	Meeee (%)	Mee
Me	8	88	88	[‌88‌]
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MM8MM=MM8	8	88	88	[‌88‌]
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Meeeeeeeeeee Meeeeeeee

8-[(8,8,8,8-Meeeeeeeeeeeeeeeeeee-8-ee)eee]eeeee-8-eee ‌88‌; Meeeeee Meeeeeeee eee α-Meeeeeeeeeee ee Meeeeeeee Meeeeeee ee Meeeeeeee:[‌88‌]

MMMMMMM: Meeeee eee ee e eeeeeeeeee eeeeee.

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References