The Effect of Conformational Freedom vs Restriction on the Rate in Asymmetric Hydrogenation: Iridium‐Catalyzed Regio‐ and Enantioselective Monohydrogenation of Dienones

• Published in: Chemistry : a European journal 2024-03, Vol.30 (13), p.e202303406-n/a
• Main Authors: Zheng, Jia, Peters, Bram B. C., Jiang, Wei, Suàrez, Lluís Artús, Ahlquist, Mårten S. G., Singh, Thishana, Andersson, Pher G.
• Format: Article
• Language: English
• Subjects: Alkanes; Alkenes; Asymmetry; Carbonyl compounds; Carbonyls; Conformation; Dienes; Enantiomers; Hydrogenation; Iridium; Iridium catalysis; Monohydrogenation; Reactivity; Regioselectivity; Transition metals
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.202303406

Transition metal‐catalyzed asymmetric hydrogenation constitutes an efficient strategy for the preparation of chiral molecules. When dienes are subjected to hydrogenation, control over regioselectivity still presents a large challenge and the fully saturated alkane is often yielded. A few successful monohydrogenations of dienes have been reported, but hitherto these are only efficient for dienes comprised of two distinctly different olefins. Herein, the reactivity of a conjugated carbonyl compound as a function of their conformational freedom is studied, based on a combined experimental and theoretical approach. It was found that alkenes in the (s)‐cis conformation experience a large rate acceleration while (s)‐trans restrained alkenes undergo hydrogenation slowly. Ultimately, this reactivity aspect was exploited in a novel method for the monohydrogenation of dienes based on conformational restriction ((s)‐cis vs (s)‐trans). This mode of discrimination conceptually differs from existing monohydrogenations and dienones constructed of two olefins similar in nature could efficiently be hydrogenated to the chiral alkene (up to 99 % ee). The extent of regioselection is even powerful enough to overcome the conventional reactivity order of substituted olefins (di>tri>tetra). This high yielding and atom‐economical protocol provides an interesting opportunity to instal a stereogenic center on a carbocycle, while leaving a synthetically useful alkene untouched. It was found that the conformation of an unsaturated carbonyl is extremely important for the reactivity in iridium catalyzed hydrogenation. This reactivity difference is used for a novel type of regioselective hydrogenation of dienes in which the (s)‐cis configured olefin is preferentially hydrogenated. The regiodiscrimination overrules the conventional reactivity order in substitution pattern in iridium‐catalyzed hydrogenation of olefins.