Palladium-catalysed formation of vicinal all-carbon quaternary centres via propargylation

Construction of two vicinal all-carbon quaternary carbon centres is of great importance due to the common presence of such units in natural and unnatural molecules with attractive functions. However, it remains a significant challenge. Here, we have developed a palladium-catalysed general coupling for the efficient connection of two tertiary carbon atoms: Specifically, propargylic carbonate has been treated with a fully loaded soft functionalized nucleophile to connect such two fully loaded carbon atoms with a simple palladium catalyst. It is observed that the central chirality in the optically active tertiary propargylic carbonates has been remembered and transferred into the products with very high efficiency. The triple bond and the functional groups such as ester, cyano and unsaturated C–C bonds make this method a relatively general solution for such a purpose due to their high synthetic versatility.


Supplementary methods
Synthesis of new tertiary propargylic carbonates 1.
Then the cooling bath was removed and the reaction mixture was then allowed to warm up to room temperature gradually with stirring for 24 h and quenched with water (20 mL). The mixture was extracted with ethyl ether (20 mL × 2), and the combined organic phase was washed by brine and dried over anhydrous Na 2 SO 4 .
Methanesulfonyl chloride (3.3 mL, d = 1.48 g/mL, 4.88 g, 42 mmol) was added dropwise within 15 min in an ice-water bath. The reaction mixture was kept stirring at this temperature for 2 h. After the reaction was complete as monitored by TLC (eluent: petroleum ether/ethyl acetate (5/1)), it was quenched with water (50 mL). The organic phase was separated, washed with a saturated NaHCO 3 aqueous solution and brine, and dried over anhydrous Na 2 SO 4 . After filtration, evaporation of the solvent, the residual was submitted to the next step without further purification.
Malononitrile (4.4 mL, d = 1.05 g/mL, 4.62 g, 70 mmol) was added dropwise within 5 min with an ice-water bath. Then the cooling bath was removed and the reaction mixture was warmed up to room temperature and stirred for 1 h. A solution of the residual from the previous step in anhydrous THF (20 mL) was injected with a syringe. The reaction mixture was stirred for 12 hours at rt as monitored by TLC (eluent: petroleum ether/ethyl acetate = 10/1). After quenching with water (40 mL), the resulting solution was extracted with ethyl acetate (40 mL × 3). The combined organic layer was washed with brine and dried over anhydrous Na 2 SO 4 . After filtration, evaporation of the solvent, and chromatography on silica gel (eluent: petroleum ether/ethyl acetate (10/1)) afforded 2c (2.3548 g, 34% over two steps) as a liquid: 1

The reaction of tertiary allyl carbonate (E)-1q with 2-benzylmalononitrile 2j
under the standard conditions. Hx-14-181     The resulting mixture was frozen with a liquid nitrogen bath, degassed and refilled with H 2 for three times. Then the reaction was allowed to stir at rt with a H 2 balloon.
After 48 h, the reaction was complete as monitored by TLC (petroleum ether / ethyl acetate = 20/1). The mixture was filtrated through a short column of silica gel with EtOAc (20 mL × 3). After evaporation, the residue was purified by chromatography