Advances in Catalytic Asymmetric Construction of Quaternary Stereogenic Centers by Conjugate Addition to β,β‐Disubstituted Nitroalkenes

Abstract

Quaternary stereogenic centers are of great importance because of their prevalence in a series of bioactive natural products and pharmaceuticals. Although the catalytic asymmetric construction of these highly congested centers poses a formidable challenge, this field has been extensively explored in the past few decades, and several elegant strategies, such as the asymmetric conjugate addition to β,β‐disubstituted nitroalkenes, have been developed. The resultant β‐nitro quaternary stereocenters can be conveniently transformed into the corresponding β‐amino quaternary stereocenters commonly found in bioactive compounds. This review summarizes the recent advances in the construction of all‐carbon quaternary or hetero‐carbon quaternary stereocenters via metal‐catalyzed and organocatalyzed asymmetric conjugate addition to β,β‐disubstituted nitroalkenes, focusing on the scope, applications, and mechanisms of these reactions.

Reactions of Alkyl β‐Nitroacrylates with Arenes in Triflic Acid: Synthesis of Oximes of Alkyl 2,3‐Diaryl‐3‐oxopropanoates

“…Apparently, the acceptor inductive effect of the protonated NO 2 and CO 2 R groups causes a shift of electrons along the system of simple σ-bonds from these protons. Similar results are observed for the shifts of signals of OMe and OEt ester groups in 1 H, and 13 C NMR spectra for cations Aa, b.…”

“…In 13 C NMR spectra, a significant downfield shift of the signal of the carboxyl carbon C 1 upon protonation is observed. Thus, the corresponding shifts are Δδ 14.6 ppm for pair 1 a-Aa and 15.7 ppm for pair 1 b-Ab.…”

“…Study of solutions of β-nitroacrylates 1 a, b in TfOH at room temperature by means of 1 H, 13 C, and 1 H-15 N HMBC NMR showed that these compounds formed stable cationic species Aa, b that were the protosolvated forms onto acceptor groups NO 2 and CO 2 R (see NMR spectra in SI). NMR data for the starting nitroacrylates 1 a, b in CDCl 3 and their protonated forms Aa, b in TfOH are presented in Table 1.…”

“…Based on this data, one may propose that carbon C 2 in Table 1. 1 H, 13 C, and 15 Based on the data obtained by NMR (Table 1) and DFT calculations (Table 2), and on our synthesis of CHal 3 -oximes, [24] as well as previous studies using TfOH superacids, [20][21][22] To demonstrate the synthetic potential of oximes 2 and 3, we carried out heterocyclization of compound 3 a into a mixture of tautomeric isoxazol-5-ones 4 (imine form) and 5 (enamine form) in EtOH solution in glass autoclave at 100 °C in 1 h at the microwave activation conditions in yield of 40 % (Scheme 3). It should be noted that the same reaction of oxime 3 b bearing 2,5-dimethylphenyl moieties did not give the corresponding isoxazolone, presumably due to steric hindrance.…”

“…General information. The NMR spectra of solutions of compounds in CDCl 3 were recorded on Bruker 400 spectrometer at 25 °C at 400 and 101 MHz for 1 H and 13 C NMR spectra respectively. The residual proton-solvent peaks CDCl 3 (δ 7.26 ppm) for 1 H NMR spectra, and the carbon signal of CDCl 3 (δ 77.0 ppm) for 13 C NMR spectra were used as references.…”