Photoredox-catalyzed Cyclopropanation And Migration Reactions Of Enamides

Radical-polar crossover(RPC)reaction combines polar reaction and radical reaction,converts radicals into carbon anion through single electron transfer(SET),and then reacts with various electrophilic reagents to generate functionalized products.It has the characteristics of high reactivity and good functional group compatibility,so it has attracted wide attention from chemists.In this paper,the reductive radical-polar crossover was used as the reaction strategy,and the following two aspects were mainly studied:(1)Photoredox-catalyzed cyclopropanation reactions of enamides.Aminocyclopropane is an important structure in active drug molecules and natural products,and is also an effective module in the development of new synthetic methods.However,in the existing synthesis methods,the synthesis of aminocyclopropane by methylene transfer reaction using Nalkenimide as substrate is still relatively rare.The reaction was carried out under 9 W Blue LEDs illumination for 24 h with N-vinylimide as the radical acceptor,halomethyl silicate as the methylene transfer reagent and DMSO as the reaction solvent.Aminocyclopropanes containing various functional groups were synthesized.Both 1,1-substituted and 1,2-substituted N-vinyl imides can be smoothly cyclopropanated.The cyclopropanation of non-terminal olefins shows that the reaction has good stereoconvergence,which provides a strategy for the synthesis of stereochemically specific aminocyclopropanes.In addition,the selective removal of the Boc protecting group promoted by zinc bromide and the removal of the phthaloyl group promoted by hydrazine hydrate provide new ideas for the synthesis of amino-substituted cyclopropanes.The reaction conditions are mild and the substrate universality is good.(2)Photoredox-catalyzed N→C acyl migration reactions of enamides.The α-aminoketone structure contains both α-amino and carbonyl functional groups,which are widely present in drug molecules and natural products.Moreover,α-amino ketones have multiple reaction sites such as amino and carbonyl groups,and are important precursors for the synthesis of other active compounds such as nitrogen-containing heterocycles and α-amino alcohols.Therefore,it is necessary to construct α-amino ketones efficiently.N-vinylimide was used as radical receptor.Alkyl silicate was used as a methylene transfer reagent,DMSO was used as a reaction solvent,and the reaction was carried out under 9 W Blue LEDs for 36 h.A series of α-amino ketones containing multiple functional groups were synthesized.Various acyl substitutions on the N atom can make the migration reaction proceed smoothly.Hantzsch is also an effective radical precursor.The competitive reaction of Boc,acyl-substituted and diacetyl-substituted imides on the N atom proves that acyl migration is an intramolecular reaction process.The deuteration reaction proves that there are carbon anions or analogues in the reaction process.The deprotection of the Boc group under the condition of trifluoroacetic acid can easily and efficiently obtain α-tert-carbon amines,which provides a new method for the synthesis of such compounds.The developed SET-induced acyl migration reaction has the characteristics of mild conditions,no alkali,no additive and no exogenous reducing agent.