Brucine Diol-Catalyzed Enantioselective Morita-Baylis-Hillman Reaction in the Presence of Brucine N-Oxide

Abstract

Brucine diol (BD) catalyzed asymmetric Morita–Baylis–Hillman (MBH) reaction is observed for the first time. Brucine N-oxide (BNO) was found to not have an effective chiral catalyst. Faster reaction rate was obtained using unsaturated ester or aromatic aldehydes in the presence of BNO. 4-Nitrobenzaldehyde and α,β-unsaturated ketone/ester were converted to the MBH adduct in moderate yields (up to 74%) with 70% ee value by this catalytic system. The mechanism of BD catalysis is probably initiated by conjugating the vicinal diol of BD to the carbonyl group of the aromatic aldehyde through hydrogen bonding. The tertiary amine of BD acts as a nucleophile to activate vinyl ketone for coupling with the carbonyl of aldehyde through an intramolecular carbonylated reaction. Finally, the breakdown of the complex caused the formation of the MBH adduct (a benzyl-allyl alcohol). The chirality of the benzyl-allyl alcohol is likely affected by the interaction of the bulky asymmetric plane of BD.

Recent Advances in Catalytic Systems for the Mechanistically Complex Morita–Baylis–Hillman Reaction

“…In 2021, Angamuthu et al described the use of a derivative of the alkaloid brucine, namely, brucine diol, as a catalyst for the asymmetric MBH reaction in combination with brucine N -oxide as a cocatalyst (Scheme ). The scope of the reaction was small, but as can be seen in Scheme , the highest enantioselectivity was observed when 2-cyclohexen-1-one was used as the nucleophilic partner (78% ee) and the lowest ee was observed when MVK was used (55% ee) with benzaldehyde.…”

“…In 2021, Angamuthu et al 33 described the use of a derivative of the alkaloid brucine, namely, brucine diol, as a catalyst for the asymmetric MBH reaction in combination with brucine N-oxide as a cocatalyst (Scheme 18). The scope of the reaction was small, Scheme 13.…”

The Application of Biocatalysis in the Preparation and Resolution of Morita‐Baylis‐Hillman Adducts and Their Derivatives

“…[34] More recently a mixed brucine N-oxide/brucine diol catalyst system was shown to give MBH adducts with moderate enantioselectivity. [35] In addition to the chiral amine catalysts, a number of chiral phosphine catalysts have also proved effective. [36] For example, Wu and co-workers [37] developed a chiral phosphinothiourea catalyst 9 for use in the enantioselective MBH reactions of aromatic aldehydes and methyl vinyl ketone (MVK).…”

“…A number of proline‐derived amine catalysts have also been applied by different workers, with enantioselectivities ranging from moderate to excellent [34] . More recently a mixed brucine N ‐oxide/brucine diol catalyst system was shown to give MBH adducts with moderate enantioselectivity [35] …”

Quinuclidine-Immobilized Porous Polymeric Microparticles as a Compelling Catalyst for the Baylis–Hillman Reaction

“…The Baylis–Hillman reaction is popular as a carbon–carbon bond-forming reaction as it exhibits operational simplicity, functional group tolerance, and achieves the synthesis of the product containing a high number of reactive functional groups. − However, this reaction is associated with the drawback of high catalyst loading requirement to achieve high conversions. Hence, it is important to develop a catalyst that is readily accessible, easily removable, and reusable.…”