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. 2020 Oct 30;11(1):5480.
doi: 10.1038/s41467-020-19293-9.

Copper(I)-catalyzed asymmetric 1,6-conjugate allylation

Chang-Yun Shi  1   2 , Zhi-Zhou Pan  2 , Ping Tian  3 , Liang Yin  4   5
Affiliations

Copper(I)-catalyzed asymmetric 1,6-conjugate allylation

Chang-Yun Shi et al. Nat Commun. .

Abstract

Catalytic asymmetric conjugate allylation of unsaturated carbonyl compounds is usually difficult to achieve, as 1,2-addition proceeds dominantly and high asymmetric induction is a challenging task. Herein, we disclose a copper(I)-NHC complex catalyzed asymmetric 1,6-conjugate allylation of 2,2-dimethyl-6-alkenyl-4H-1,3-dioxin-4-ones. The phenolic hydroxyl group in NHC ligands is found to be pivotal to obtain the desired products. Both aryl group and alkyl group at δ-position are well tolerated with the corresponding products generated in moderate to high yields and high enantioselectivity. Moreover, both 2-substituted and 3-substituted allylboronates serve as acceptable allylation reagents. At last, the synthetic utility of the products is demonstrated in several transformations by means of the versatile terminal olefin and dioxinone groups.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Prior arts in catalytic asymmetric conjugate allylation and our work.
a Failed copper(I)-catalyzed asymmetric conjugate allylation. b Reported catalytic asymmetric conjugate allylation. c This work: copper(I)-catalyzed asymmetric conjugate 1,6-allylation.
Fig. 2
Fig. 2. Substrate scope of (E)-2,2-dimethyl-6-alkyl-4H-1,3-dioxin-4-ones in the 1,6-conjugate allylationa.
Various aliphatic substituents at δ-position are studied.
Fig. 3
Fig. 3. Substrate scope of (E)-2,2-dimethyl-6-aryl-4H-1,3-dioxin-4-ones in the 1,6-conjugate allylationa.
Various aromatic substituents at δ-position are studied.
Fig. 4
Fig. 4. Preliminary investigation of 1,6-conjugate allylation with 2-substituted allylboronates (6–8)a.
Both aromatic and aliphatic substituents at δ-position are tried.
Fig. 5
Fig. 5. Diastereoselective 1,6-conjugate allylation.
a The 1.6-conjugate allylation with (E)-allylBPin. b The 1,6-conjugate allylation with (Z)-allylBPin.
Fig. 6
Fig. 6. Control experiments with different NHC-ligands.
The importance of the presence of a phenol group in NHC-ligands is demonstrated.
Fig. 7
Fig. 7. Transformations of product 5d.
a Ir-catalyzed hydroboration. [Ir(COD)Cl]2 (5 mol %), dppm (Ph2PCH2PPh2) (10 mol %), HBPin (2 equiv), CH2Cl2, rt. b Olefin Metathesis. Hoveyda-Grubbs II catalyst (10 mol %), 4-methylstyrene (2 equiv), CH2Cl2, 40 °C. c Transformation to β-keto-ester. MeOH, K2CO3, rt. d Transformation to α,β-unsaturated ester. (1) NaBH4, MeOH, 0 °C; (2) MsCl, Et3N, CH2Cl2, 0 °C to rt. e Transformation to pyrazole. NH2NH2•HCl (2 equiv), MeOH, reflux.
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