[CrimpJiggler]

1st generation asymmetric synthesis is "substrate control" while 3rd generation asymmetric synthesis is "reagent control". Whats the difference? I thought the substrate is a reagent. I noticed a few hydroboration reactions that were called reagent controlled asymmetric syntheses. I know that borane can't be a chiral reagent so I'm very confused about what 3rd generation asymmetric is and how it differs from first generation asymmetric synthesis.

[discodermolide]

1st generation asymmetric synthesis is "substrate control" while 3rd generation asymmetric synthesis is "reagent control". Whats the difference? I thought the substrate is a reagent. I noticed a few hydroboration reactions that were called reagent controlled asymmetric syntheses. I know that borane can't be a chiral reagent so I'm very confused about what 3rd generation asymmetric is and how it differs from first generation asymmetric synthesis.

In substrate control the stereochemistry of the product is determined by that of the starting materials. Reagent control it is controlled by the configuration of the reagent conferring a specific transition state to a reaction. Look for Paterson's work on Adol chemistry.

[fledarmus]

One example of reagent controlled stereochemistry would be using a chiral ligand on a catalyst. While the ligand is never incorporated into the final product (as a substrate would be), it can control the stereochemistry of the reaction such that the stereochemistry of the final product is determined by the stereochemistry of the ligand.

[Dan]

I wasn't familiar with these classifications, found some info here.

[fledarmus]

Ah, nice definitions Dan. My example would have been classed as fourth-generation then, sorry.

[Dan]

Yeah, so I suppose 3rd gen is something like hydrating an achiral alkene by hydroboration with a stoichiometric chiral dialkylborane (e.g. Icp₂BH), followed by peroxide workup?