Rapid Evaluation of the Mechanism of Buchwald–Hartwig Amination and Aldol Reactions Using Intramolecular 13C Kinetic Isotope Effects
Year: 2020
Type: article
Abstract: A practical approach is introduced for the rapid determination of 13 C kinetic isotope effects that utilizes a “designed” reactant with two identical reaction sites. The mechanism of the Buchwald–Hartwig amination of tert -butylbromobenzene with primary and secondary amines is investigated under synthetically relevant catalytic conditions using traditional inter molecular 13 C NMR methodology at natural abundance. Switching to 1,4-dibromobenzene, a symmetric bromoarene as the designed reactant, the same experimental 13 C KIEs are determined using an intra molecular KIE approach. This rapid methodology for KIE determination requires substantially less material and time compared to traditional approaches. Details of the Buchwald–Hartwig amination mechanism are investigated under varying synthetic conditions, namely a variety of halides and bases. The enantioselectivity-determining step of the l -proline catalyzed aldol reaction is also evaluated using this approach. We expect this mechanistic methodology to gain traction among synthetic chemists as a practical technique to rapidly obtain high-resolution information regarding the transition structure of synthetically relevant reactions under catalytic conditions.
Source: ACS Catalysis
Institution: Binghamton University
Language: English
Topic: Chemical Reaction Mechanisms
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W3112338201