Hydrogen‐bond‐enabled dynamic kinetic resolution of axially chiral amides mediated by a chiral counterion

Non‐biaryl atropisomers are valuable in medicine, materials, and catalysis, but their enantioselective synthesis remains a challenge. Herein, a counterion‐mediated O‐alkylation method for the generation of atropisomeric amides with an er up to 99:1 is outlined. This dynamic kinetic resolution is enabled by the observation that the rate of racemization of atropisomeric naphthamides is significantly increased by the presence of an intramolecular O−H⋅⋅⋅NCO hydrogen bond. Upon O‐alkylation of the H‐bond donor, the barrier to rotation is significantly increased. Quantum calculations demonstrate that the intramolecular H‐bond reduces the rotational barrier about the aryl–amide bond, stabilizing the planar transition state for racemization by approximately 40 kJ mol−1, thereby facilitating the observed dynamic kinetic resolution

Reasoning as we read:establishing the probability of causal conditionals

Indicative conditionals of the form if p then q (e.g., if student tuition fees rise, then applications for university places will fall) invite consideration of a hypothetical event (e.g., tuition fees rising) and of one of its possible consequences (e.g., applications falling). Since a rise in tuition fees is an uncertain event with equally uncertain consequences, a reader may believe the statement to a greater or lesser extent. As a conditional is read, the earliest point at which this probabilistic evaluation can take place is as the consequent clause is wrapped up (e.g., as the critical word fall is read in the example above). Wrap-up processing occurs at the end of the clause, as it is evaluated and integrated into the evolving discourse representation. Five sources of probability may plausibly influence the evaluation of a conditional as it is wrapped up; these are P(p), P(q), P(pq), P(q|p), and P(not-p or q). A total of 128 conditionals were constructed, with these probabilities calculated for each item in a pretest. The conditionals were then embedded in vignettes and read by 36 participants on a word-by-word basis. Using linear mixed-effects modeling, we found that wrap-up reading times were predicted by pretest ratings of P(p) and P(q|p). There was no influence of P(q), P(pq), or P(not-p or q) on wrap-up reading times. Our findings are consistent with the suppositional theory of conditionals proposed by Evans and Over (2004) but do not support the mental-models theory advanced by Johnson-Laird and Byrne (2002)