Electronic Effect on the Kinetics of the Diaza-Cope Rearrangement

Abstract

Hammett plot reveals that there is a significant electronic effect on the rate of resonance assisted hydrogen bond (RAHB) directed diaza-Cope rearrangement reaction with a rho value of 1.6. DFT computation shows that the rearrangement reaction becomes thermodynamically more favorable for the substrates with electron withdrawing substituents. A substrate with the nitro substituent (1a) reacts about 50-fold faster than that with the methoxy substituent (1g).

Mimicking Nature to Make Unnatural Amino Acids and Chiral Diamines

“…[64] Consistent with experimental data, DFT computation reveals that 38b is more stable than 38a by about 3.2 kcal/mol, which translates to an equilibrium concentration ratio of about 230:1 for [38b]: [38a] at 25°C (K 3 = 230). It appears that the equilibrium [Equation (5)] favors the side with the more electron-rich imine.…”

“…[5-6, [64][65] A chiral pyridoxal model (1) can be used to make not only natural amino acids, but also unnatural α-amino acids, with excellent stereoselectivity (Scheme 4). Fundamental knowledge gained from these studies can be used to make an achiral pyridoxal model 15 that interacts in a highly stereoselective way with a wide variety of small molecules (including α-, β-and γ-amino acids, peptides, amino alcohols and diamines) in a unified way (Figure 10).…”

“…The first reaction involves double imine rearrangement by a [3,3] sigmatropic reaction, while the second reaction involves a single imine rearrangement. The equilibria for both reactions are controlled by weak forces including a) hydrogen bonding, [63] b) electronic effecst [64] and c) steric effects. [65] Nature has tuned and optimized these effects for pyridoxamine [Equation (4), Scheme 9].…”

Ionic Liquids as Precatalysts in the Highly Stereoselective Conjugate Addition of α,β‐Unsaturated Aldehydes to Chalcones

“…[22] It should be noted that the para-methoxy-substituted 12 formed in 67 % yield requires a much longer reaction time than any of the other 1,6-ketoesters an effect that has previously been described in Cope rearrangements (vide infra). [23] With regard to the alcohol reaction partner ethanol and benzyl alcohol react to give the corresponding ethyl ester and benzyl ester in 53 and 68 % yield with a d.r. of 20:1, respectively (entries 14 and 15).…”

Resonance‐Assisted Hydrogen Bonding as a Driving Force in Synthesis and a Synthon in the Design of Materials

“…RAHB-assisted regioselective CÀCc leavage in (E/Z)-2-[2-(4-substitutedphenyl)hydrazono]-4,4,4-trifluoro-1-(thiophen-2-yl)butane-1,3dione. [109,110,[273][274][275][276][277][278][279][280] DCR allows the preparationc hiral vicinal diamines including C 2 symmetric diaryl and dialkyl diamines, as well as unsymmetrical alkyl-aryl and aryl-aryld iamines with excellent yields and enantiopurities. Eur.J.…”