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. 2023 Apr 28;25(16):2767-2770.
doi: 10.1021/acs.orglett.3c00571. Epub 2023 Apr 18.

Synthesis of 2-Cyanomethyl Indane Derivatives via Pd-Catalyzed Alkene Difunctionalization Reactions of Alkyl Nitriles

Alma R Perez  1 , Evan C Bornowski  1 , Lei Chen  1 , John P Wolfe  1
Affiliations

Synthesis of 2-Cyanomethyl Indane Derivatives via Pd-Catalyzed Alkene Difunctionalization Reactions of Alkyl Nitriles

Alma R Perez et al. Org Lett. .

Abstract

The synthesis of indanes bearing substituted cyanomethyl groups at C2 is achieved through Pd-catalyzed coupling reactions between 2-allylphenyl triflate derivatives and alkyl nitriles. Related partially saturated analogues were generated from analogous transformations of alkenyl triflates. The use of a preformed BrettPhosPd(allyl)(Cl) complex as a precatalyst was essential for the success of these reactions.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1.
Scheme 1.
Previous Worka,b
Scheme 2.
Scheme 2.. Reactions of Aryl Triflatesa,b
aConditions: 1.0 equiv aryl triflate, 1.4 equiv nitrile, 1.4 equiv LiHMDS, 4 mol % BrettPhosPd(allyl)(Cl), 6 mol % BrettPhos, dioxane (0.1 M), 80 °C, 16 h. Reactions were conducted on a 0.2 mmol scale. Diastereomeric ratios were determined by 1H NMR analysis. bYields are average isolated yields of two or more experiments. Yields in parentheses are NMR yields. cThe reaction was conducted at 95 °C. dThe reaction was conducted at 70 °C. eThe reaction was conducted on a 1.0 mmol scale.
Scheme 3.
Scheme 3.. Reactions of Alkenyl Triflatesa,b
aConditions: 1.0 equiv alkenyl triflate, 1.4 equiv nitrile, 1.4 equiv LiHMDS, 4 mol % BrettPhosPd(allyl)(Cl), 6 mol % BrettPhos, dioxane (0.1 M), 80 °C, 16 h. Reactions were conducted on a 0.2 mmol scale. Diastereomeric ratios were determined by 1H NMR analysis. bYields are average isolated yields of two or more experiments. Yields in parentheses are NMR yields.
Scheme 4.
Scheme 4.
Mechanism
See this image and copyright information in PMC

References

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    1. For related transformations of amine, alcohol, or indole nucleophiles, see:

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