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. 2021 Nov 16;12(1):6627.
doi: 10.1038/s41467-021-26955-9.

Rhodium-catalyzed intermolecular enantioselective Alder-ene type reaction of cyclopentenes with silylacetylenes

Dongquan Zhang  1 , Miaomiao Li  1 , Jiajia Li  1 , Aijun Lin  2 , Hequan Yao  3
Affiliations

Rhodium-catalyzed intermolecular enantioselective Alder-ene type reaction of cyclopentenes with silylacetylenes

Dongquan Zhang et al. Nat Commun. .

Abstract

The Alder-ene type reaction between alkenes and alkynes provides an efficient and atom-economic method for the construction of C-C bond, which has been widely employed in the synthesis of natural products and other functional molecules. The intramolecular enantioselective Alder-ene cycloisomerization reactions of 1,n-enynes have been extensively investigated. However, the intermolecular asymmetric version has not been reported, and remains a challenging task. Herein, we describe a rhodium-catalyzed intermolecular enantioselective Alder-ene type reaction of cyclopentenes with silylacetylenes. A variety of chiral (E)-vinylsilane tethered cyclopentenes bearing one quaternary carbon and one tertiary carbon stereocenters are achieved in high yields and enantioselectivities. The reaction undergoes carbonyl-directed migratory insertion, β-H elimination and desymmetrization of prochiral cyclopentenes processes.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Transition metal-catalyzed Alder-ene type reaction.
a Intramolecular enantioselective Alder-ene type cycloisomerization reaction (well-developed). b Intermolecular Alder-ene type reaction of internal alkenes (Trost’s work). c Intermolecular enantioselective Alder-ene type reaction (this work).
Fig. 2
Fig. 2. Substrate scope.
Reaction conditions: 1a (0.10 mmol), 2a (0.30 mmol), [Rh(COD)OMe]2 (2.5 mol%), L6 (6.0 mol%), PhMe2CCO2H (60 mol%), NaBARF (10 mol%), DCM (1.0 mL), 80 oC, 36 h, under argon. Isolated yields, d.r. > 20:1, E/Z > 20:1, determined by 1H NMR analysis. The ee values were determined by chiral HPLC analysis. a[Rh(COD)OMe]2 (5.0 mol%), 72 h. b72 h. c[Rh(COD)OMe]2 (5.0 mol%). d[Rh(COD)Cl]2 (5.0 mol%), L5 (12 mol%), Ph3CCO2H (60 mol%), NaBARF (20 mol%), d.r. > 20:1, Z/E > 20:1.
Fig. 3
Fig. 3. Further studies on the reaction.
a Gram-scale experiment. b Transformations of the products. aPd/C (10 wt %), B2(OH)4, H2O, DCM, rt. bLiAlH4, 1,4-dioxane, 0 oC-80 oC, 15 h. cNBS, Ag2CO3, HFIP, rt, 2 h. dTFA, DCM, 60 oC, 12 h. ePd(dba)2, TBAF·3H2O, Iodobenzene, THF, rt, 24 h. c Mechanistic studies. d Proposed mechanism.
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References

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