The real value of new chemical entities is in production on a multigram scale.
You can enter new chemical space and be assured that there will be ample material available for any future plan with new scaffolds.
We used continuous-flow chemistry to scale up [2+2] photocycloaddition. This resulted in an abundance of new, strained scaffolds that could easily be further derivatized.
Allyl and homoallyl precursors 1 and 5 were prepared from commercial building blocks. Small-scale [2+2] photocycloadditions in a Rayonet photoreactor were attempted under continuous flow to shorten reaction times and improve yields. Scaffolds 2 and 3 and homologous compound 6 were isolated in high yield after chromatography.
Although more than 5 g could be produced per day, we deemed this output to be insufficient for library production. Construction of a higher throughput system, with a reactor volume of >100 mL, allowed the preparation of 50 g per day of new conformationally restricted three-dimensional aminoketone scaffolds. These products are ready for use in library synthesis.
This is the impact of discovery chemistry on our new chemical space initiative!