Nickel-catalyzed allylic defluorinative alkylation of trifluoromethyl alkenes with reductive decarboxylation of redox-active esters

Synthesis of functionalized gem-difluoroalkenes was achieved through nickel-catalyzed allylic defluorinative alkylation of trifluoromethyl alkenes with reductive decarboxylation of redox-active esters.


S38
List of NHPI esters.
Preparation of NHPI esters using carboxylic acids and N-hydroxyphthalimide.

Preparation of Alkyl Bromides
List of alkyl bromides.
Preparation of alkyl bromides.

Examples Described in
Following general procedure, 1a and 2a were used. The product was isolated by column chromatography as white solid (57.5 mg, 0.184 mmol, 92%).
Following general procedure, 1a and 2b were used. The product was isolated by column chromatography as white solid (59.4 mg, 0.182 mmol, 91%).
Following general procedure, 1a and 2c were used. The product was isolated by column chromatography as colorless oil (51.6 mg, 0.164 mmol, 82%).
Following general procedure, 1a and 2g were used. The product was isolated by column chromatography as colorless oil (80.2 mg, 0.194 mmol, 97%).
Following general procedure, 1b and 2j were used. The product was isolated by column chromatography as colorless oil (61.0 mg, 0.156 mmol, 78%).
Following general procedure, 1a and 2k were used. The product was isolated by column chromatography as colorless oil (75.3 mg, 0.180 mmol, 90%).
Following general procedure, 1a and 2l were used. The product was isolated by column chromatography as colorless oil (66.2 mg, 0.166 mmol, 83%).

Selectivity (desired C-F cleavage product : addition by-product)
Following general procedure, 1a and 2n were used. The product was isolated by column chromatography as white solid (49.7 mg, 0.142 mmol, 71%) Selectivity (desired C-F cleavage product : addition by-product) > 50:1.

One-Pot Synthesis at Gram Scale
One-pot synthesis at gram scale.

Examples Described in
Following general procedure, 1c and 2a were used. The product was isolated by column chromatography as white solid (47.9 mg, 0.140 mmol, 70%).
Following general procedure, 1e and 2b were used. The product was isolated by column chromatography as colorless oil (54.8 mg, 0.160 mmol, 80%).
Following general procedure, 1g and 2b were used. The product was isolated by column chromatography as colorless oil (56.5 mg, 0.166 mmol, 83%).
HRMS spectra for 3sa.  Table 5 General procedure for examples described in Table 5.

Examples Described in
Following general procedure, 1b and 4a were used. The product was isolated by column chromatography as colorless oil (71.3 mg, 0.174 mmol, 87%).

Examples Described in Scheme 1
List of substrates in Scheme 1.
Following general procedure, 1b and 4e were used. The product was isolated by column chromatography as colorless oil (83.6 mg, 0.184 mmol, 92%).
HRMS spectra for 5be.  Following general procedure, 1b and 4f were used. The product was isolated by column chromatography as colorless oil (72.1 mg, 0.154 mmol, 77%).

Examples Described in Scheme 2
Model reaction with TDAE. Following general procedure, 1a and 2r were used. The product was isolated by column chromatography as colorless oil (76.4 mg, 0.170 mmol, 85%).