Cinchonidinium acetate as a convenient catalyst for the asymmetric synthesis of cis-stilbenediamines

Abstract

Inexpensive and readily available cinchonidinium acetate is an effective catalyst for the syn-selective aza-Henry reaction of arylnitromethanes and aryl imines. The resulting masked cis-stilbenediamine products are produced in excellent diastereoselectivity and good enantioselectivity, and enantiopure material can be achieved via recrystallization. The features of the cinchona catalyst needed for selectivity are discussed, with specific emphasis on formation of a kinetically controlled syn-product without epimerization of the highly acidic α-nitro stereocenter.

Fluorine-induced diastereodivergence discovered in an equally rare enantioselective syn-aza-Henry reaction

“…[31][32][33][34] To summarize, across Types I-IV, anti-diastereoselection is observed when using non-uorinated nitroalkanes. This is observed regardless of catalyst (1 or 2), reaffirming reports with PTC, 21 BAM, 35 and a wide range of other catalysts 4,36-38 with alkylsubstituted nitronates, and PTC [24][25][26] or BAM 14 catalysts applied to aryl-substituted nitronates. Departing from this behavior 39 for enantioselective aza-Henry reactions, Shibasaki's report is a standout.…”

“…23,24 Kozlowski iden-tied cinchonidinium acetate (C3$HOAc) as an effective homogeneous catalyst for Type I product (Ph/ t BuC 6 H 4 : 97 : 3 anti : syn, 70% ee). 25 Finally, Duan used a urea/tetralkyl ammonium bifunctional catalyst (C4) to provide 6a (Ph/Ph) in 99 : 1 anti : syn and 99% ee. 26,27 In Type II (Alkyl/Ar) additions, the reaction of aryl nitronates with alkyl aldimines have been established as anti-selective.…”

Catalytic asymmetric synthesis of 1,2-diamines

“…Enantiomeric β-nitroamine derivatives 320 were obtained with good yields and diastereo- and enantioselectivities. Walvoord and Kozlowski 236 employed cinchonidinium acetate as a phase-transfer catalyst for the asymmetric synthesis of cis -stilbene diamines. The reaction of α-aryl nitromethanes with N -Boc benzylidene imines 161 using cinchonidine (10 mol%) and HOAc (10 mol%) in dichloromethane at −30 °C provided products anti - 320 (R 1 = Ar) with 29–99% yields, 97 : 3–99 : 1 dr and 26–79% ee.…”

Peer Review #2 of "One-pot multicomponent nitro-Mannich reaction using a heterogeneous catalyst under solvent-free conditions (v0.1)"

“…Yet despite the utility, research in the nitro-Mannich reaction has not been very popular because the β-nitroamine product is often prone to retro-addition and epimerisation [24]. Moreover, the addition of nitronates to imines is not thermodynamically favoured due to the difference between the pKa values of nitroalkane (pKa ~9) and the β-nitroamine product (pKa ~35) [2].…”