Hydroxymethylation of alkynes with N-methylamines and water enabled by Co/photoredox dual catalysis

doi:10.1016/S1872-2067(26)65076-0

Abstract

Abstract:

Water is an ideal hydrogen or oxygen source in chemical synthesis. However, many organic reactions are unable to utilize this potential or even incompatible with aqueous conditions. Here, we report a synergistic visible light organophotoredox Co-catalyzed highly regio- and stereoselective hydroxymethylation of alkynes with N-methylamines and water. This method employs water as both hydrogen (H) and oxygen (O) donor, with N-methyl trialkylamines serving as C1 synthon and photoredox reductant, thereby eliminating exogenous oxygenated C1 reagents. A variety of tri-substituted allylic alcohols have been obtained with excellent regio- (up to >19:1 rr) and stereoselectivity (> 19:1 E/Z for over 30 examples). Mechanistic studies reveal two critical water assistant processes involving selective C-N cleavage of N-methylamines generating formaldehyde and subsequent regioselective reductive hydroxymethylation of alkynes via photoredox cobalt dual catalysis.

Key words: Hydroxymethylation, Water, Methylamine, Photoredox cobalt dual catalysis, Alkyne

Yan-Lin Li, Ning-Xin Guo, Jia-Ting Bi, Ling-Yu Xue, Yue-Lu Zhu, You-Dong Shao, Ji-Bao Xia. Hydroxymethylation of alkynes with N-methylamines and water enabled by Co/photoredox dual catalysis[J]. Chinese Journal of Catalysis, 2026, 87: 197-205.

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URL: https://www.cjcatal.com/EN/10.1016/S1872-2067(26)65076-0

https://www.cjcatal.com/EN/Y2026/V87/I8/197

Figures/Tables 7

Fig. 1. Selective coupling of N-methyl amines via photoredox metal dual catalysis.

Fig. 2. Initial result for the unusual hydroxymethylation. Reaction conditions: 1 (0.2 mmol), 2 (0.4 mmol), H2O (5.0 eq.), 4CzIPN (2 mol%), CoCl2 (10 mol%), Xantphos (10 mol%), MeCN (2 mL), 5 W blue LED, r.t., 24 h; Yield, rr, E/Z were determined by crude 1H NMR with 1,1,2,2 tetrachloroethane as an internal standard.

Table 1 Summary of the effects of reaction parameters on the reaction efficiency a.

Entry	Change from “standard conditions”	Yield (%)	rr	E/Z
1	none	81 (78)^b	>19:1	>19:1
2	PPh₃ instead of PCy₃	70	>19:1	>19:1
3	NiXantphos instead of PCy₃	61	13:1	>19:1
4	DPEphos instead of PCy₃	67	3.3:1	>19:1
5	DPPF instead of PCy₃	37	4:1	>19:1
6	DPPE instead of PCy₃	41	6:1	>19:1
7	DPPP instead of PCy₃	36	4:1	>19:1
8	DCyPE instead of PCy₃	20	12:1	>19:1
9	DMF instead of MeCN	45	>19:1	>19:1
10	MeOH instead of MeCN	21	>19:1	>19:1
11	2c (4 eq.)	79	>19:1	>19:1
12	H₂O (10 eq.)	80	>19:1	>19:1
13	without 2c	N.R.	—	—
14	without H₂O	N.R.	—	—

Fig. 3. Reaction scope. Reaction conditions: alkyne (0.2 mmol), 2c (0.4 mmol), H2O (5.0 eq.), 4CzIPN (2 mol%), CoCl2 (10 mol%), PCy3 (20 mol%), MeCN (2 mL), 5 W blue LED, r.t., 24 h. if otherwise noted. Isolated yield of product is provided. The regioselectivity (rr) for alkyne and the stereoselectivity (E/Z) of the product were determined by crude 1H NMR. a The reaction was performed with 8.0 mmol alkyne 1 as the substrate. b With DCyPE as ligand.

Fig. 4. Transformation and application of the products. Reagents and conditions: (A) m-CPBA, DCM, r.t., 75%; (B) Chloramine-T, NBS (20 mol%), MeCN, r.t., 71%; (C) SOCl2, DCM, 0 °C, 79%; (D) RuCl3 (10 mo%), NaIO4, MeCN/CCl4/H2O, r.t., 49%; (E) PPh3, phthalimide, DIAD, THF, 0 °C r.t., 41%; (F) PPh3, DIAD, THF, 0 °C r.t., 61%.

Fig. 5. Control experiments.

Fig. 6. Plausible reaction pathway.

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