Diphenylprolinol Silyl Ether as Catalyst of an Asymmetric, Catalytic, and Direct Michael Reaction of Nitroalkanes with α,β-Unsaturated Aldehydes

Abstract

A catalytic enantioselective direct conjugate addition of nitroalkanes to alpha,beta-unsaturated aldehydes using diphenylprolinol silyl ether as an organocatalyst has been developed. Using this methodology as a key step, short syntheses of therapeutically useful compounds have also been accomplished.

Continuous-Flow Stereoselective Synthesis in Microreactors: Nucleophilic Additions to Nitrostyrenes Organocatalyzed by a Chiral Bifunctional Catalyst

“…Now that the basic concepts, the procedures, and the apparatus have been established for the stereoselective nucleophilic addition of 2a to 1a, the scope of this study was expanded to the synthesis of compound 4b (Scheme 1), which is an advanced intermediate for the preparation of the GABA B receptor agonist Baclofen [18].…”

Mechanism of Oxidative Amidation of Nitroalkanes with Oxygen and Amine Nucleophiles by Using Electrophilic Iodine

“…NH 4 Cl solution (20 mmol) and extracted with CH 2 Cl 2 . The combined organic layers were washed with brine (10 mL), dried (MgSO 4 ), filtered and concentrated under reduced pressure to give crude 4a, which was columned via silica gel chromatography (Hex/EA = 5/1) to give pure 4a (470mg, 60%) as a white solid (stored at low temperature without light).…”

“…The aqueous was then extracted with CH 2 Cl 2 (25×2mL, pre-cooled to -30 ºC ). The organic phase was dried over MgSO 4 General procedure: Nitroalkane [13] (1.105g, 5 mmol) was dissolved in10 mL MeOH, then K 2 CO 3 (1.035 g, 7.5 mmol) was added to stirred at R.T. for 10 min, then filter solid to collect solution. Cooling the solution to -30 , and added I 2 (1.27g, 5 mmol), slowly warm to 0, untile the solution become darken, then pour the reaction mixture to 100 mL water, and extract by CH 2 Cl 2 (100 mL).…”

“…Subsequent removal of methanol, changing the solvent to CH 3 CN, cooling to 0 °C, adding the pre-prepared complex 15 in one-portion, stirring for <5 min, quenching with sat. NH 4 Cl solution, and purifying the crude by silica gel chromatography afforded the α-iodo nitroalkane 4a in 75 % yield.…”

Organocatalytic Conjugate Addition in Stereoselective Synthesis

“…33 A simple transformation of the Michael adducts by oxidation-reduction sequence led to commercial drugs in high enantiopurity. Using the same methodology, Palomo et al disclosed the addition of nitromethane for the two-pot synthesis of Rolipram (Sigma-Aldrich, St. Louis, MO), another commercial drug (Scheme 11.6, eq 2).…”