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Alkene Photo-Isomerization Inspired by Vision Colin M. Pearson and Thomas N. Snaddon Department of Chemistry, Indiana University, 800 E. Kirkwood Avenue, Bloomington, Indiana 47405, United States
photosensitive membrane-bound opsin protein (Figure 1, top). The contra-thermodynamic isomerization is catalyzed by a putative isomerohydrolase and proceeds via an acylated all-trans-retinol (Figure 1, bottom).4 Interestingly, (−)-riboflavin has been reported to catalyzed the contra-thermodynamic photoisomerization of all-trans-retinol (E → Z).5 Taken together, these provide the basis for Gilmour’s design blueprint where (E)-cinnamonitriles would serve as truncated retinal scaffolds, and their isomerization is catalyzed by (−)-riboflavin/visible light. This builds on their earlier work where the retinal polyene chromophore required for photoexcitation is replaced by an arene ring, and the function of the protonated opsin-Schiff base is mimicked by an electron-withdrawing group (Scheme 1). The direction of catalysis and hence stereochemical outcome would derive from nonbonding interactions (A1,3-strain) in the (Z)-isomer, which would force the aromatic ring out of conjugation. This disruption to conjugation would result in inefficient excitation of (Z)-configured products and permit selective sensitization of the arene-conjugated (E)-isomer.6 Within Gilmour’s delineation of substrate design, the contra-thermodynamic photoisomerization of polarized alkenes is efficiently catalyzed by (−)-riboflavin. In this present study, readily accessible (E)-cinnamonitriles undergo contra-thermodynamic isomerization in excellent yield and with high (Z)-stereoselectivity (Scheme 2A).3 This extends the platform of contra-thermodynamic photoisomerizations reported previously by the same laboratory (Scheme 2B) and provides a useful, general and operationally trivial synthetic approach.7 Gilmour and co-workers have rigorously interrogated the mechanism and concluded both singlet and triplet pathways are likely operative. The apparent mechanistic promiscuity resulting from (−)-riboflavin catalysis has been noted previously by the same laboratory and leveraged in a bioinspired cascade catalysis synthesis of coumarins (Scheme 2C).7a Here, (−)-riboflavin catalyzes two distinct
Catalyst-controlled isomerization of retinal mimics.
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lkenes are amongst the most versatile functional groups in synthetic organic chemistry. They can be readily functionalized using a broad toolbox of reagent and catalyst-based methods, which provide more complex molecules for a host of applications. Alkenes are most commonly and conveniently prepared using Wittig- and Julia-type reactions of carbonyl electrophiles; however, control over the product alkene geometry can be challenging.1 Characteristic of these well-established methods is predominant access to one alkene isomer but not the other, whose synthesis might require multi-step preparation via an alternative sequence. Modern recourse to catalysis has provided stereospecific alkyne functionalization reactions,2 but these often lack the generality and functional group tolerance of the aforementioned reagent-based carbonyl olefination methods. Overall, the preparation of single alkene isomers remains a challenging problem, and it is of continuing interest and importance to develop conceptually innovative methods for their synthesis. In line with this, Gilmour and co-workers have described the riboflavincatalyzed E → Z photo-isomerization of functionalized cinnamonitriles, an approach inspired by ocular retinal isomerization.3
Overall, the preparation of single alkene isomers remains a challenging problem, and it is of continuing interest and importance to develop conceptually innovative methods for their synthesis. Isomerization of the polyene chromophore 11-cis-retinal to all-trans-retinal is key to vision. This thermodynamically favored process occurs in the retina and proceeds via a protonated Schiff base formed between 11-cis-retinal and a © XXXX American Chemical Society
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DOI: 10.1021/acscentsci.7b00376 ACS Cent. Sci. XXXX, XXX, XXX−XXX
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ACS Central Science Scheme 1. Substrate Design
Figure 1. Thermodynamic retinal isomerization in the visual cycle occurs by photoisomerization of a protonated opsin−Schiff base (top). The contra-thermodynamic photoisomerization is though to occur via all-trans-retinol (bottom).
processes that proceed via energy transfer (ET) and single electron transfer SET), respectively. Nature has long served as inspiration for the design of new catalysts and catalytic methods for laboratory synthesis. This has been particularly true in the area of organocatalysis where N-heterocyclic carbenes (NHC) and amine Lewis base catalysts can trace their origins to biological mechanisms.8 Similarly, Gilmour’s alkene photoisomerization borrows extensively from nature’s principles and, through careful substrate design, provides a useful and operationally straightforward method by which to access stereodefined polarized alkenes that are challenging to prepare by other means. The significance of this work
Similarly, Gilmour’s alkene photoisomerization borrows extensively from nature’s principles and, through careful substrate design, provides a useful and operationally straightforward method by which to access stereodefined polarized alkenes that are challenging to prepare by other means. extends far beyond organic photocatalysis9 and alkene isomerization. A rich palette of chemistry exists for the B
DOI: 10.1021/acscentsci.7b00376 ACS Cent. Sci. XXXX, XXX, XXX−XXX
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ACS Central Science
Scheme 2. (−)-Riboflavin-Catalyzed Photoisomeriztion of β-Substituted Cinnamyl Derivatives: (A) Cinnamonitriles; (B) Cinnammyl Carbonyl Substrates; (C) Cinnamic Acids−One-Pot Coumarin Synthesis
stereoselective and stereospecific functionalization of alkenes, and thus the impact of this method likely lies in its union with subsequent catalytic asymmetric alkene functionalization methods.
(3) Metternich, J. B.; Artiukhin, D. G.; Holland, M. C.; von BremenKuehne, M.; Neugebauer, J.; Gilmour, R. J. Org. Chem. 2017, DOI: 10.1021/acs.joc.7b01281. (4) Ebrey, T.; Koutalos, Y. Prog. Retinal Eye Res. 2001, 20, 49. (5) Walker, A. G.; Radda, G. K. Nature 1967, 215, 1483. (6) For a transition metal catalyzed photocatalytic isomer-
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ization of allylic amines, see: Singh, K.; Staig, S. J.; Weaver, J. D. J. Am. Chem. Soc. 2014, 136, 5275.
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E-mail:
[email protected].
(7) (a) Metternich, J. B.; Gilmour, R. J. Am. Chem. Soc. 2016, 138, 1040. (b) Metternich, J. B.; Gilmour, R. Synlett 2016, 27, 2541. (c) Metternich, J. B.; Gilmour, R. J. Am. Chem. Soc. 2015, 137, 11254. (8) (a) For a recent review of NHCs in organocatalysis, see:
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGEMENTS ACKNOWLEDGMENTS We thank the Indiana University, the National Institutes of Health (01R01GM121573), and the American Chemical Society Petroleum Research Fund (55734-DNI) for generous financial support.
Flanigan, D. M.; Romanov-Michailidis, F.; White, N. A.; Rovis, T. Chem. Rev. 2015, 115, 9307. (b) For a review of amine Lewis base catalysts in organocatalysis, see: Mukherjee, S.; Yang, J. W.; Hoffmann, S.; List, B. Chem. Rev. 2007, 107, 5471. (9) For an instructive review of organic photocatalysis, see: Romero, N. A.; Nicewicz, D. A. Chem. Rev. 2016, 116, 10075.
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REFERENCES REFERENCES (1) For instructive reviews concerning Wittig and Julia olefination methods, see: (a) Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863. (b) Blakemore, P. R. J. Chem. Soc., Perkin Trans. 1 2002, 2563. (2) For alkyne reductions, see: (a) Modern Reduction Methods, Andersson, P. G., Munslow, I. J., Eds.; Wiley-VCH: Weinheim, 2008; For excellent recent reviews concerning the transition metal catalyzed functionalization of alkynes, see:. (b) Dorel, R.; Echavarren, A. M. Chem. Rev. 2015, 115, 9028. (c) Chinchilla, R.; Nájera, C. Chem. Rev. 2014, 114, 1783. C
DOI: 10.1021/acscentsci.7b00376 ACS Cent. Sci. XXXX, XXX, XXX−XXX
