Asymmetric Synthesis of 1,4‐Dicarbonyl Compounds from Aldehydes by Hydrogen Atom Transfer Photocatalysis and Chiral Lewis Acid Catalysis

Abstract

Enantioenriched 1,4-dicarbonyl compounds are versatile synthons in natural product and pharmaceutical drug synthesis.W eh erein report am ild pathway for the efficient enantioselective synthesis of these compounds directly from aldehydes through synergistic cooperation between an eutral eosin Yh ydrogen atom transfer photocatalyst and ac hiral rhodium Lewis acid catalyst. This method is distinguished by its operational simplicity,a bundant feedstocks, atom economy,and ability to generate products in high yields (up to 99 %) and high enantioselectivity (up to 99 %ee).Scheme 1. Synthesis of 1,4-dicarbonyl compounds through asymmetric acyl radical conjugateaddition.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.Scheme 5. Gram-scale synthesis and further synthetic diversification.Scheme 6. Proposed reaction mechanism for the merged HATphotocatalysis and asymmetric Lewis acid catalysis. RHAT = reverse hydrogen atom transfer.

Photoinduced site-selective alkenylation of alkanes and aldehydes with aryl alkenes

“…Activated C sp3 -H bonds were also examined. Ethers (28)(29)(30), amides (31) and alkylbenzenes (32) were all found to be competent substrates (38-67%). Notably, substituted tetrahydropyrans afforded alkenylation products (29 and 30) with excellent regio-and diastereoselectivity.…”

“…Although much progress has been achieved, the developed systems usually require stoichiometric peroxides and a large excess of the C-H partner (over 40 equivalents of the alkanes), and the substrate scopes are limited to simple hydrocarbons and aromatic aldehydes. In pursuing methods for olefin construction [25][26][27] and photomediated C-H bond functionalization [28][29][30][31] , we aspired to develop an auxiliary-free and oxidant-free strategy for C sp3 -H and C sp2 (O)-H alkenylation with the C-H substrate as the limiting reagent (Fig. 1c).…”

Recent developments in enantioselective photocatalysis

“…They have recently developed an example using an indazole-based ligand [ 116 ] to add to their well-established benzoxazole and benzothiazole ligands. Such complexes have then been used for α-functionalisations [ 117 ], RCAs [ 118 ], and cycloaddition reactions [ 119 ]. As much of Meggers work has been summarised previously [ 120 ], here we will include only recent examples from each reaction class.…”

“…A recent example of these catalysts being used for RCAs exploited Eosin Y as an external HAT photocatalyst to generate acyl radicals 305 • from aldehydes 305 , which then add to the Lewis acid complex 306 enantioselectively to form α-carbonyl radicals 307 • ( Scheme 51 ) [ 118 ]. The reverse HAT step completes the photocatalytic cycle and produces the complexed RCA product 307 , which can be displaced by another substrate molecule 308 to finish the cycle and release the desired enantioenriched products 309 in moderate yields and excellent enantioselectivities (19 examples, up to >99:1 er).…”

Bromine as a Visible-Light-Mediated Polarity-Reversal Catalyst for the Functionalization of Aldehydes

“…[4][5][6][7][8] In this context, the emergence of photocatalysis has provided enormous opportunities for C-H functionalization through direct photo hydrogen atom transfer (HAT) catalysis or by the synergistic combinations of photoredox with HAT catalysis. [9][10][11][12][13][14][15][16][17][18] Aldehydes, one of the most abundant and readily available feedstocks, are enabled to generate acyl radicals to achieve umpolung reactivity by photo-induced HAT in a step-and atom-economic fashion. [19][20] However, the acceptors of acyl radicals were limited to electron-de cient alkenes and radical trappers containing electron-withdrawing leaving groups, [21][22][23][24][25] to result in an electrophilic radical intermediate to turn over the redox-neutral photocatalytic cycle ( Fig.…”