Palladium-Catalyzed Three-Component Selective Aminoallylation of Diazo Compounds

Abstract

In spite of the valuable perspective on rapid accessing α,α-disubstituted α-amino acid derivatives, a three-component reaction of diazo compounds, amines and allyl esters remains as an unexplored challenge, probably because of the fore-seeable side reactions arising from each two reactants. In this work, we describe a novel Xantphos-containing dinuclear palladium complex enabled geminal aminoallylation of diazocarbonyl compounds, which provides a range of quaternary α-amino esters selectively. Direct N-H insertion, allylic alkylation of amino nucleophiles and diene formation were not observed under standard conditions. Mechanistic studies indicated that the Xantphos-containing palladium complex with a Pd/P ratio of 1/1 was optimal to enable the reaction to achieve high selectivity. A relayed pathway via allylation of N-H insertion product or [2,3]-sigmatropic rearrangement of a ylide intermediate was unlikely. We believe that the current strategy on palladium-catalyzed selective carbene difunctionalization could be general to construct quaternary carbon centers, and inspire more transformations in related field.

Selective Construction of All-Carbon Quaternary Centers via Relay Catalysis of Indole C–H Functionalization/Allylic Alkylation

“…Furthermore, when the amount of Xantphos was decreased to 0.5 mol %, the reaction still provided the product 5aa in 83% yield (entry 7). Intriguingly, a Rh(I) salt ([Rh(cod) 2 ]BF 4 ) and other metal sources, including Cu(MeCN) 4 (PF 6 ), [RuCl(pcymene)] 2 , or [PdCl(ally)] 2 , 13 were found to be largely ineffective in promoting the reaction (entries 8−11). In addition, the control experiment further established the essential role of Rh 2 (Oct) 4 in this catalytic system (entry 12).…”