Levin, E.; Mavila, S.; Eivgi, O.; Tzur, E.; Lemcoff, N.G. “Regioselective Chromatic Orthogonality with Light-Activated Metathesis Catalysts” Angew. Chem. Int. Ed. 2015, Advance Article. DOI: 10.1002/anie.201500740
The control of molecular bond formation is fundamental to synthetic chemists. Recently, a creative synthetic route for selective ring formation by utilizing different wavelengths to orthogonally control a reaction pathway has been disclosed. Lemcoff and co-workers employ their photoisomerizable sulfur chelated catalyst and a polysilyl protecting group to provide a sleek route to five and six membered rings (Figure 1).
Figure 1. Chromatically orthogonal reagents
To begin, Lemcoff and co-workers investigated the feasibility of using their sulfur chelated catalyst in tandem with the tris(trimethylsilyl)silyl protecting group. As hoped, the latent cis-dichloro isomer of the sulfur chelated catalyst, which has been shown to isomerize to the more active trans isomer upon exposure to 350 nm light,1 could be used orthogonally with the tris(trimethylsilyl)silyl protecting group that is cleaved upon exposure to 254 nm light.2 Secondly, the authors studied the use of the bulky tris(trimethylsilyl)silyl protecting group to sterically control regioselectivity in ring closing metathesis. When submitting unprotected triene 2 to ring closing metathesis, the sulfur chelated catalyst favored the six membered ring synthesis (Figure 2). However, the use of the bulky protecting group favored ring closure to five membered ring heterocycle 3, reversing the regioselectivity of the RCM (ring closing metathesis) reaction. Finally, after some optimization to account for catalyst decomposition that can occur during irradiation, Lemcoff and co-workers succeeded in designing a one-pot procedure that yielded the heterocycles with modest yields. In summary, starting with the tris(trimethylsilyl)silyl triene 1, the authors were able to produce either the six-membered alkene 4 or the five-membered alkene 5 simply by judiciously controlling the exposure order of the two wavelengths (254 nm and 350 nm).
Figure 2. Chromatically orthogonal system.
This recent work from the laboratory of Lemcoff is an elegant application of their photoisomerizable sulfur chelated catalyst. Leveraging the orthogonality in wavelength activation between the catalyst and protecting group delivers a great one-pot reaction pathway. Hopefully, in the future we will see more examples in which the manipulation of wavelengths can be used to control the overall molecular architecture of the final product.
1Ben-Asuly, A.; Aharoni, A.; Eiesendruck, C.E.; Vidavsky, Y.; Goldberg, I.; Straub, B.F.; Lemcoff, N.G. Organometallics 2009, 28, 4652-4655.
2Brook, M.A; Gottardo, C.; Balduzzi, S.; Mohomed, M. Tetrahedron Lett. 1997, 38, 6997-7000.