SnAP Reagent

23 January, 2018 / by SK / in Reactions

4318

Overall Score4

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Contribution to Medicinal Chemistry
Criteria #5

General Characteristics

SnAP (Sn(tin) Amine Protocol) reagents provide an easy access to a variety of saturated heterocycles and amines containing a spiro skeleton. The simple two-step procedure involves initial imine formation and oxidative cyclization. The reagents are stable and can be handled easily, and many types are commercially available.

Increasing the saturation of heterocycles (proportion of sp³ carbons) in pharmaceutical compounds is expected to have beneficial physicochemical effects.

General References

Vo, C.-V.; Mikutis, G.; Bode, J. W. Angew. Chem. Int. Ed. 2013, 52, 1705. DOI: 10.1002/anie.201208064

Luescher, M. U.; Vo, C.-V.; Bode, J. W. Org. Lett. 2014, 16, 1236. DOI: 10.1021/ol500210z

Vo, C.-V.; Luescher, M. U.; Bode, J. W. Nat. Chem. 2014, 6, 310. doi:10.1038/nchem.1878

Siau, W.-Y.; Bode, J. W. J. Am. Chem. Soc. 2014, 136, 17726. DOI: 10.1021/ja511232b

Geoghegan, K.; Bode, J. W. Org. Lett. 2015, 17, 1934. DOI: 10.1021/acs.orglett.5b00618

Luescher, M. U.; Bode, J. W. Angew. Chem. Int. Ed. 2015, 54, 10884. DOI: 10.1002/anie.201505167

Luescher, M. U.; Bode, J. W. Org. Lett. 2016, 18, 2652. DOI: 10.1021/acs.orglett.6b01099

<Reviews>

Vo, C.-V.; Bode, J. W. J. Org. Chem. 2014, 79, 2809. DOI: 10.1021/jo5001252

Luescher, M. U.; Geoghegan, K.; Nichols, P. L.; Bode, J. W. Aldrichim. Acta 2015, 48, 43. [PDF]

Reaction Mechanism

Examples

When used for ketone substrates, spiro-products can be synthesized, which are challenging to access otherwise.

Tin-free and photo-activated SLAP (Silicon Amine Protocol) reagents have been reported.^[1]

Experimental Procedure
Experimental Tips
References

[1] (a) Hsieh, S.-Y.; Bode, J. W. Org. Lett. 2016, 18, 2098. DOI: 10.1021/acs.orglett.6b00722 (b) Hsieh, S-H.; Bode, J. W. ACS Cent. Sci. 2017, 3, 66. DOI: 10.1021/acscentsci.6b00334