Tsuji-Trost Cyclization of Disulfonamides: Synthesis of 12-Membered, 11-Membered, and Pyridine-Fused Macrocyclic Triamines

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Authors

Ali, Rameez
Anugu, Sreenivasa R.
Chawla, Reena
Demillo, Violeta G.
Goulinet-Mateo, Florian
Gyawali, Sagar
Hamal, Sunil
Jones, Dylan E.
Lamprecht, Katrin
Le, Truc D. T.

Issue Date

2019

Type

Article

Language

en_US

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Abstract

Macrocyclic triamine disulfonamides can be synthesized by double Tsuji-Trost N-allylation reaction of open-chain disulfonamides with 2-alkylidene-1,3-propanediyl bis(carbonates). The previously used Atkins-Richman macrocyclization method generally gives lower yields and requires more tedious purification of the product. Solvent, palladium source, ligand, and concentration have all been varied to optimize the yields of two key 12-membered ring bioactive compounds, CADA and VGD020. The new approach tolerates a wide range of functional groups and gives highest yields for symmetrical compounds in which the acidities of the two sulfonamide groups are matched, although the yields of unsymmetrical compounds are still generally good. The method has also been extended to the synthesis of 11-membered rings, pyridine-fused macrocycles, and products bearing an ester or aryl substituent on the exocyclic double bond.

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Citation

Ali, R., Anugu, S., Chawla, R., Demillo, V. G., Goulinet-Mateo, F., Gyawali, S., … Bell, T. W. (2019). Tsuji–Trost Cyclization of Disulfonamides: Synthesis of 12-Membered, 11-Membered, and Pyridine-Fused Macrocyclic Triamines. ACS Omega, 4(1), 1254–1264. doi:10.1021/acsomega.8b02555

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ACS Omega

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In Copyright (All Rights Reserved)

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ISSN

2470-1343

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