A borane-mediated palladium-catalyzed reductive allylic alkylation of α,β-unsaturated carbonyl compounds†

The development of the palladium-catalyzed allylic alkylation of in situ generated boron enolates via tandem 1,4-hydroboration is reported. Investigation of the reaction revealed insights into specific catalyst electronic features as well as a profound leaving group effect that proved crucial for achieving efficient allylic alkylation of ester enolates at room temperature and ultimately a highly preparatively useful synthesis of notoriously challenging acyclic all-carbon quaternary stereocenters. The method demonstrates boron enolates as viable pro-nucleophiles in transition-metal catalyzed allylic alkylation, potentially opening up further transformations outside their traditional use.

Analytical data are in accordance with the literature values. 4
Pivoyl chloride (0.5 mL, 4.0 mmol) was added in dropwise manner. In another round bottom flask was dissolved (R)-4-methyloxazolidin-2-one (652.6 mg, 4 mmol) in 40 mL of dry THF under a nitrogen atmosphere. A solution of n-BuLi (1.5 mL, 4.0 mmol, 2.67 M in hexanes) was added dropwise. The reaction mixture was stirred for 5 minutes. The resulting solution was added to the former reaction mixture in a dropwise manner for about 10 minutes at 0 º C. The reaction mixture was allowed to warm to r.t. and was stirred overnight. After completion of the reaction, the solvent was evaporated under vacuum. Water was added, and the reaction mixture was extracted with ethyl acetate, washed with brine, concentrated, and purified by flash silica gel column chromatography eluting with 10 % ethyl acetate in petroleum ether to afford 1.07 g of white solid product in 58% yield. melting point 95-97 º C.  75, 153.29, 137.72, 129.14, 128.80, 128.68, 128.46, 127.71, 127.68, 127.63, 127.52, 127.13, 126.20, 125.88, 79.86, 69.75, 58.31, 28.39, 13.23.
Analytical data are in accordance with the literature values. 5

C. General procedure of reductive allylic alkylation reactions Procedure A:
Dicyclohexylborane (1.5 eq) was obtained from the glovebox by addition to an oven-dried microwave vial that was cooled in the vacuum chamber of the glovebox. The solid was suspended in freshly distilled THF, and the corresponding acrylate (1.5 eq) was added dropwise while cooling on an ice bath. After addition, ice was removed from the water/ice mixture, and the water was allowed to warm to r.t. Upon warming to 5 Inui, M.; Hosokawa, S.; Nakazaki, A.; Kobayshi, S. Tet. Lett. 2005, 46, 3245-3248. S9 r.t., a clear solution was obtained. The hydroboration was allowed to stir for an additional 30 minutes to ensure complete hydroboration. Solid Pd(PPh 3 ) 4 (0.05 eq) was quickly added by removing the septum with a stream of argon above the solution. After replacement of the septum, a stream of argon was passed over the solution with a needle as an outlet. Cinnamyl N,N-dimethyl ethanolamine carbonate (1.0 eq) was added dropwise. Precipitate was observed within minutes. The reaction was allowed to react for 1 h. to ensure complete conversion. The solution was diluted with 90%/10% diethyl ether/pentane solution and passed through a short plug of silica. The solvent was removed under rotary evaporation, and the oil was purified by flash silica gel chromatography (90/10 diethyl ether/pentane) to afford the products.

Procedure B:
The standard procedure was employed using auxiliary substrate (1.0 eq), dicyclohexylborane (1.1 eq), CpPdcinnamyl (0.02 eq), W001-1 (0.02 eq), and allylic carbonate (1.5 eq) in dry THF. This solution was added to solid dicyclohexylborane at r.t. After 1 hr. of stirring, the solution was gradually heated to 40 º C, and the solution turned clear after 20 min. The solution was allowed to cool to r.t., and was then cooled on a salt/ice bath (-20 º C). Catalyst solution was generated in THF was added to the solution of boron enolate.
The reaction mixture was allowed to equilibrate to temperature, and allylic carbon was added dropwise over 5 min. The solution was allowed to warm overnight, and the product was purified by flash silica gel chromatography to afford the product.

(E)-2-(dimethylamino)ethyl (3-(4-methoxyphenyl)allyl) carbonate (5d)
To a stirring solution of 4-methoxy cinnamyl alcohol (0.492g, 3.0 mmol, 1.0 eq) in THF at -78⁰ C was added a solution of n-butyllithium (1.20 mL, 3.0 mmol, 1.0 eq, 2.5 M in hexanes) dropwise. The solution was allowed to stir for 20 minutes, and acyl imidazole (1.099g, 6.0 mmol, 2.0 eq) was added dropwise. The solution was allowed to stir at -78⁰ C until precipitate was observed. The reaction was warmed to r.t., and 40 mL of water was added, followed by 40 mL of diethyl ether. The organic layer was separated, and the aqueous phase was extracted with 40 mL diethyl ether. The solvent was dried over anhydrous magnesium sulfate, filtered, and evaporated to an oil. The product was purified by flash silica gel chromatography (pure DCM to 95% DCM / 5% triethylamine) to afford a clear liquid (0.3404 g, 41% yield).