Uploaded September 2021 | Updated September 2026, 2 weeks ago
Another introductory video on enantioselective catalysis in Organic Chemistry. Here secondary ketones can be synthesised in high enantiomeric excess from the parent ketone by a CBS reduction reaction. Essentially the CBS reduction is a chiral version of the more familiar reagent sodium borohydride, NaBH4.
#chemistry #organicchemistry #ochem #orgo #science #stem #education #learn #catalyst #catalysis #synthesis #molecule #stereochemistry
The CBS reduction is one of the most reliable catalytic asymmetric transformations in organic chemistry. It take prochiral ketones and performs a nucleophilic hydride reduction with very high levels of enantioselectivity for the chiral secondary alcohol product, provided that there is good steric differentiation between the two groups attached to the carbonyl group. Products are easy to purify and are often synthesised in excellent enantiomeric excess (or diastereomeric ratio if applicable). This example of a catalytic reduction used Lewis acid and Lewis base activation of reagent and reactant is easy to perform in the lab and easy to work up and purify the product.
The CBS catalyst itself has synthesised from the naturally occurring amino acid proline, which is available cheaply as either enantiomer from our natural world. Proline is first esterified and then the ester treated with a Grignard reagent to form an aminoalcohol. Coordination of a mono-alkyl boronic acid forms the key Lewis acid catalyst which consists of a 5,5-bicyclic ring structure, which has a convex face and a concave face. The prochiral ketone coordinates and is activated on the convex face. The nearby nitrogen atom is then free to act as a Lewis base on borane (BH3), activating it as a borohydride and hence also as a nucleophile or reducing agent. With this double activation, an intramolecular reaction for the reduction of the ketone is set up, and as it is intramolecular the reaction will proceed at a higher rate like this as opposed to any other possible intermolecular reaction. The intramolecular delivery of the hydride nucleophile occurs via a six-membered ring transition state. However, the lowest energy transition state is not a chair conformation as is common to reactions that are well-predicted by the Zinnerman-Traxler model. The CBS reduction transition state is a boat conformation, and so the lowest energy transition state places the largest substituent on the prochiral ketone reactant into the pseudo-equatorial position and out of the way of clashing sterically with any alkyl group on the catalyst itself.
Another introductory video on enantioselective catalysis in Organic Chemistry. Here secondary ketones can be synthesised in high enantiomeric excess from the parent ketone by a CBS reduction reaction. Essentially the CBS reduction is a chiral version of the more familiar reagent sodium borohydride, NaBH4.
#chemistry #organicchemistry #ochem #orgo #science #stem #education #learn #catalyst #catalysis #synthesis #molecule #stereochemistry
The CBS reduction is one of the most reliable catalytic asymmetric transformations in organic chemistry. It take prochiral ketones and performs a nucleophilic hydride reduction with very high levels of enantioselectivity for the chiral secondary alcohol product, provided that there is good steric differentiation between the two groups attached to the carbonyl group. Products are easy to purify and are often synthesised in excellent enantiomeric excess (or diastereomeric ratio if applicable). This example of a catalytic reduction used Lewis acid and Lewis base activation of reagent and reactant is easy to perform in the lab and easy to work up and purify the product.
The CBS catalyst itself has synthesised from the naturally occurring amino acid proline, which is available cheaply as either enantiomer from our natural world. Proline is first esterified and then the ester treated with a Grignard reagent to form an aminoalcohol. Coordination of a mono-alkyl boronic acid forms the key Lewis acid catalyst which consists of a 5,5-bicyclic ring structure, which has a convex face and a concave face. The prochiral ketone coordinates and is activated on the convex face. The nearby nitrogen atom is then free to act as a Lewis base on borane (BH3), activating it as a borohydride and hence also as a nucleophile or reducing agent. With this double activation, an intramolecular reaction for the reduction of the ketone is set up, and as it is intramolecular the reaction will proceed at a higher rate like this as opposed to any other possible intermolecular reaction. The intramolecular delivery of the hydride nucleophile occurs via a six-membered ring transition state. However, the lowest energy transition state is not a chair conformation as is common to reactions that are well-predicted by the Zinnerman-Traxler model. The CBS reduction transition state is a boat conformation, and so the lowest energy transition state places the largest substituent on the prochiral ketone reactant into the pseudo-equatorial position and out of the way of clashing sterically with any alkyl group on the catalyst itself.
