Ligand-controlled divergent copper-catalyzed enantioselective dihydroallylation and ring-opening hydroallylation of methylenecyclopropanes

doi:10.1016/S1872-2067(26)65158-3

Abstract

Abstract:

We report a tunable, ligand-controlled protocol for the copper-hydride-catalyzed functionalization of methylenecyclopropanes (MCPs) with allyl phosphates. This divergent methodology enables selective access to two distinct classes of unsaturated scaffolds, dictated by the specific phosphine ligand employed. When the chiral bisphosphine ligand (S,S)-Ph-BPE is utilized, the reaction proceeds via an enantioselective dihydroallylation cascade, affording nonconjugated chiral 1,9-dienes with high yields and excellent enantioselectivities (up to > 99% ee). Alternatively, switching the ligand to Xantphos confines the reaction at the ring-opening stage, selectively delivering nonconjugated 1,6-dienes via mono-allylation. Mechanistic studies support a stepwise pathway initiated by hydrocupration and β-carbon elimination, wherein the mono-allylated intermediate can be isolated and subsequently converted into the di-allylated product. The versatility of this platform is further demonstrated through a modular one-pot cascade employing two distinct allylic phosphates to generate structurally complex chiral dienes. Additionally, the catalytic system has been extended to carbonylative hydroallylation, providing efficient access to α,β-unsaturated ketones and chiral ketones. This strategy represents a robust approach for the stereoselective construction of diverse dienes and carbonyl-containing frameworks from strained ring systems.

Key words: Copper catalysis, Hydroallylation, Divergent Synthesis, Enantioselective, Carbonylation

Yang Yuan, Fangbei Ge, Xiao-Feng Wu. Ligand-controlled divergent copper-catalyzed enantioselective dihydroallylation and ring-opening hydroallylation of methylenecyclopropanes[J]. Chinese Journal of Catalysis, 2026, 89: 444-452.

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URL: https://www.cjcatal.com/EN/10.1016/S1872-2067(26)65158-3

https://www.cjcatal.com/EN/Y2026/V89/I10/444

Figures/Tables 8

Scheme 1. Copper hydride catalyzed hydroallylation of unsaturated C-C bonds. (a) CuH-catalyzed enantioselective hydroallylation of alkenes. (b) CuH-catalyzed anti-Markovnikov hydroallylation of alkynes. (c) This work: CuH-catalyzed selective hydroallylation of MCPs.

Table 1 Optimization of the reaction conditions a.

Entry	Variation from above conditions	Yield of 3a (%)	ee of 3a (%)	Yield of 4a (%)
1	None	87 (73)^b	99	trace
2	(MeO)₂MeSiH instead of PMHS	45	95	9
3	(EtO)₂MeSiH instead of PMHS	51	99	nd
4	THF instead of DME	85	99	12
5	1,4-Dioxane instead of DME	71	99	15
6	2a-1 instead of 2a	37	98	6
7	2a-2 instead of 2a	28	97	4
8	Without LiO^tBu	0	—	0
9	L2 instead of L1	trace	—	24
10	L3 instead of L1	trace	—	43
11	L4 instead of L1	5	nd	17
12	L5 instead of L1	0	—	54
13^c	L5 instead of L1	0	—	70 (61)^b

Scheme 2. Substrate scope for enantioselective dihydroallylation. Reaction conditions: 1 (0.1 mmol), 2 (0.3 mmol), CuCl (10 mol%), (S,S)-Ph-BPE (12 mol%), LiOtBu (3 equiv.), PMHS (4 equiv.), 30 °C and DME (0.5 mL). Isolated yields; ee’s were determined by chiral HPLC.

Scheme 3. Substrate scope for ring-open hydroallylation. Reaction conditions: 1 (0.1 mmol), 2 (0.15 mmol), CuCl (10 mol%), Xantphos (12 mol%), LiOtBu (2 equiv.), PhMe2SiH (3 equiv.), 30 °C and THF (0.5 mL). Isolated yields.

Scheme 4. One-pot cascade hydroallylation with two different allylic phosphates. Reaction conditions: 1a (0.1 mmol), allylic phosphate (0.15 mmol), CuCl (10 mol%), Xantphos (12 mol%), LiOtBu (2 equiv.), PhMe2SiH (3 equiv.), and THF (0.5 mL) were stirred at 30 °C for 20 h, then, the second allylic phosphate (0.15 mmol), CuCl (10 mol%), (S,S)-Ph-BPE (12 mol%), LiOtBu (0.2 mmol) and (MeO)2MeSiH (0.2 mmol) was added and the mixture was stirred for another 20 h. Isolated yields; ee’s were determined by chiral HPLC.

Scheme 5. Synthetic transformations.

Fig. 1. Proposed reaction pathways.

Scheme 6. Substrate scope for carbonylative hydroallylation. Reaction conditions: 1 (0.1 mmol), 2 (0.2 mmol), CuCl (10 mol%), (rac)-Segphos (12 mol%), LiOtBu (2 equiv.), PMHS (3 equiv.), 50 °C, DCE (0.5 mL) and CO (10 bar). a Reaction conditions: 1a (0.1 mmol), 2a (0.3 mmol), CuCl (10 mol%), (S,S)-Ph-BPE (12 mol%), LiOtBu (3 equiv.), PMHS (4 equiv.), 50 °C, DCE (0.5 mL) and CO (10 bar). Isolated yields, ee was determined by chiral HPLC.

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