Diastereoselective Allylation of Aldehydes by Dual Photoredox and

Communication Cite This: J. Am. Chem. Soc. 2018, 140, 12705−12709

pubs.acs.org/JACS

Diastereoselective Allylation of Aldehydes by Dual Photoredox and Chromium Catalysis J. Luca Schwarz,‡ Felix Schäfers,‡ Adrian Tlahuext-Aca, Lukas Lückemeier, and Frank Glorius* Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, 48149 Münster, Germany

Downloaded via UNIV OF VIRGINIA on November 22, 2018 at 13:21:12 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.

S Supporting Information *

ABSTRACT: Herein, we report the redox-neutral allylation of aldehydes with readily available electronrich allyl (hetero-) arenes, β-alkyl styrenes and allyldiarylamines. This process was enabled by the combination of photoredox and chromium catalysis, which allowed a range of homoallylic alcohols to be prepared with high levels of selectivity for the anti diastereomer. Mechanistic investigations support the formation of an allyl chromium intermediate from allylic C(sp3)−H bonds and thus significantly extends the scope of the venerable Nozaki− Hiyama−Kishi reaction.

T

he allylation of carbonyls is an important class of reaction in organic synthesis for the formation of C(sp3)−C(sp3) bonds.1 The resulting homoallylic alcohol products are valuable and versatile building blocks, which are frequently employed in natural product synthesis.2,3 Among the important carbonyl allylation protocols of Brown, Roush, Leighton and Krische,1 one of the most well established methods for the allylation of aldehydes is the Nozaki− Hiyama−Kishi (NHK) reaction (Figure 1a).4 This chromiummediated reaction proceeds with excellent chemoselectivity for aldehydes over otherwise reactive ketones or esters and furthermore selectively forms the anti diastereomer independent of the original allyl C−C double bond geometry. The NHK reaction has therefore become a powerful synthetic tool in the synthesis of complex bioactive molecules.5 However, the generation of toxic chromium waste in stoichiometric amounts remains a concern. This problem has inspired elegant work by Fürstner6 and others7 on the design of catalytic-in-chromium NHK-type reactions. These catalytic processes typically utilize allylic halides in combination with a silyl Lewis acid and an excess of manganese as a terminal reductant to afford silylprotected homoallylic alcohols. From a strategic and atom economic viewpoint, the direct functionalization of more readily available allylic C−H bonds in a catalytic redox-neutral process would therefore be highly desirable. In recent years, the functionalization of C−H bonds by photoredox catalysis has received widespread attention,8 yet the use of carbonyls as coupling partners in this context remains underdeveloped. Two major pathways for the C−C bond formation between alkyl radicals and carbonyls can be distinguished (Figure 1b). First, alkyl radicals can add directly to C−O double bonds.9,10 However, this step is reversible and thermodynamically unfavored, thus limiting the applicability of this process, especially for intermolecular reactions.11 Second, © 2018 American Chemical Society

Figure 1. (a) Diastereoselective allylation of aldehydes with allyl chromium species (Nozaki−Hiyama−Kishi reaction). (b) (Nondiastereoselective) alkylation of carbonyls via photoredox catalysis. (c) This work: Diastereoselective allylation of aldehydes by dual photoredox and chromium catalysis.

aromatic carbonyls can be reduced to long-lived ketyl radicals, which can undergo radical−radical coupling with suitable alkyl radicals.12 Importantly, both mechanistic pathways proceed without diastereocontrol.13 Considering this, and given the success of the combination of photoredox and transition metal catalysis for C−C and C−X bond formation,14 we questioned if a similar dual catalytic approach could be developed to provide facile access to allyl chromium intermediates and thus allow the chemo- and diastereoselective allylation of aldehydes from versatile radical precursors (Figure 1c). We envisaged the dual catalytic process illustrated in Figure 2. First, this process would initiate by photoexcitation of a suitable photocatalyst, such as [Ir(dF(CF3)ppy)2(dtbbpy)][PF6] (IrIII, dF(CF3)ppy = 2(2,4-difluorophenyl)-5-(trifluoromethyl)pyridine, dtbbpy = Received: July 29, 2018 Published: September 14, 2018 12705

DOI: 10.1021/jacs.8b08052 J. Am. Chem. Soc. 2018, 140, 12705−12709

Communication

Journal of the American Chemical Society

Figure 3. Standard reaction conditions.

detected (19:1 d.r.) of the desired homoallylic alcohol product 6lj in a single batch. As reported previously for chromium allyl species, the reaction proved to be highly chemoselective for

Given the success of methyl eugenol in this transformation, we wondered if β-alkyl styrenes could also be used in this allylation protocol. These would be attractive precursors as they can be easily synthesized from the corresponding carbonyl compound via classical olefination procedures and would give rise to the same allyl radical intermediates after the oxidation and deprotonation sequence. First, a commercially available cis/trans mixture of methyl isoeugenol was employed to test this proposal. To our delight, the allylated product 6ea was obtained exclusively in 83% yield as a single diastereomer, supporting our hypothesis. The scope was further extended to other alkoxylated β-methyl styrenes (6ga−ia), including benzyloxy substituents that can be readily removed to yield the free hydroxy groups. Next, we examined whether 1,2amino alcohols, which are important structures found in a number of pharmaceuticals and natural products,23 could be prepared using our method starting from readily available allylic amines. We were pleased to find that N-allyl-diarylamines were indeed reactive, affording the desired products 6ja−ma in high yields with excellent diastereoselectivies. In 12707

DOI: 10.1021/jacs.8b08052 J. Am. Chem. Soc. 2018, 140, 12705−12709

Journal of the American Chemical Society aldehyde functionalization; other carbonyls did not afford the homoallylic alcohol products. To highlight this high chemoselectivity, an Epiandrosterone derivative, containing multiple different carbonyl moieties, was also employed in this allylation protocol. Pleasingly, the ketone and ester groups did not affect the reaction and the desired product 6lr was isolated in 68% yield. Additionally, as enantioselective NHK-type allylations are well studied5 and to examine future developments of our dual catalytic approach, preliminary studies toward an enantioselective variant were conducted. To our delight, when enantiopure Nakada’s carbazole-based bisoxazoline ligand7c was tested under our reaction conditions with Nallyl-diphenylamine and 4-fluorobenzaldehyde (4a), a moderate enantiomeric excess (20% ee) for product 6la was obtained (see the Supporting Information for details). Although modest, these results clearly demonstrate the feasibility of an enantioselective protocol, which remains the focus of ongoing work. Finally to highlight the robustness of this allylation protocol, an additive-based screen was performed (see Supporting Information for details).24 From this screen, 13 out of 14 additives had only little influence on the yield, illustrating the functional group tolerance of this mild reaction protocol. Importantly, nitrile and ketone additives were also recovered quantitatively. In conclusion, we have disclosed a mild, redox-neutral and scalable method for the diastereoselective allylation of aldehydes with unfunctionalized allyl (hetero-) arenes enabled by the combination of photoredox and chromium catalysis. Mechanistic investigations support the involvement of a chromium allyl species that reacts via a six-membered transition state with the aldehyde. A variety of readily available allyl arenes were reactive, including indoles, carbazoles and electron-rich allyl benzenes. Additionally, the substrate scope was extended for the α-C(sp3)−H functionalization of β-alkyl styrenes and allyl-diarylamines. Aliphatic and aromatic aldehydes are both equally reactive and selective and can be functionalized in the presence of ketones and esters. To the best of our knowledge, this work represents the first example of dual photoredox and chromium catalysis. Overall, we expect this approach to be widely employed in selective aldehyde functionalizations.

■

■

ACKNOWLEDGMENTS

■

REFERENCES

Dedicated to Prof. Holger Butenschön on the occasion of his 65th birthday. We thank the Alfried Krupp von Bohlen and Halbach Foundation (J.L.S.) and the Deutsche Forschungsgemeinschaft (Leibniz Award) for generous financial support. We thank Max Lübbesmeyer and Andre Kemna for experimental support, Mario Wiesenfeldt, Dr. Michael James, Santanu Singha and Satobhisha Mukherjee for helpful discussion, and Dr. Constantin G. Daniliuc and Birgit Wibbeling (all WWU Münster) for the X-ray crystallographic analysis.

(1) For selected reviews on carbonyl allylation, see: (a) Yus, M.; González-Gómez, J. C.; Foubelo, F. Chem. Rev. 2013, 113, 5595. (b) Kim, S. W.; Zhang, W.; Krische, M. J. Acc. Chem. Res. 2017, 50, 2371. (c) Wang, P.-S.; Shen, M.-L.; Gong, L.-Z. Synthesis 2018, 50, 956. (d) Spielmann, K.; Niel, G.; de Figueiredo, R. M.; Campagne, J.M. Chem. Soc. Rev. 2018, 47, 1159. (e) Huo, H.-X.; Duvall, J. R.; Huang, M.-Y.; Hong, R. Org. Chem. Front. 2014, 1, 303. (f) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207. (2) For selected syntheses of natural products containing a homoallylic alcohol moiety, see: (a) Kawamura, S.; Chu, H.; Felding, J.; Baran, P. S. Nature 2016, 532, 90. (b) Reddy, L. R.; Saravanan, P.; Corey, E. J. J. Am. Chem. Soc. 2004, 126, 6230. (c) Gao, X.; Hall, D. G. J. Am. Chem. Soc. 2005, 127, 1628. (d) Kang, S. H.; Kang, S. Y.; Kim, C. M.; Choi, H.-w.; Jun, H.-S.; Lee, B. M.; Park, C. M.; Jeong, J. W. Angew. Chem., Int. Ed. 2003, 42, 4779. (e) Wang, Y.; Ju, W.; Tian, H.; Tian, W.; Gui, J. J. Am. Chem. Soc. 2018, 140, 9413. (3) For selected recent natural product syntheses utilizing the formation of homoallylic alcohol intermediates, see: (a) Lu, Z.; Zhang, X.; Guo, Z.; Chen, Y.; Mu, T.; Li, A. J. Am. Chem. Soc. 2018, 140, 9211. (b) Schmid, M.; Grossmann, A. S.; Wurst, K.; Magauer, T. J. Am. Chem. Soc. 2018, 140, 8444. (c) Nicolaou, K. C.; Rhoades, D.; Kumar, S. M. J. Am. Chem. Soc. 2018, 140, 8303. (4) (a) Okude, Y.; Hirano, S.; Hiyama, T.; Nozaki, H. J. Am. Chem. Soc. 1977, 99, 3179. (b) Namba, K.; Wang, J.; Cui, S.; Kishi, Y. Org. Lett. 2005, 7, 5421. (5) For selected reviews, see: (a) Fürstner, A. Chem. Rev. 1999, 99, 991. (b) Gil, A.; Albericio, F.; Á lvarez, M. Chem. Rev. 2017, 117, 8420. (c) Tian, Q.; Zhang, G. Synthesis 2016, 48, 4038. (d) Hargaden, G. C.; Guiry, P. J. Adv. Synth. Catal. 2007, 349, 2407. (e) Hargaden, G. C.; Guiry, P. J. In Stereoselective Synthesis of Drugs and Natural Products; Andrushko, V.; Andrushko, N., Eds.; John Wiley & Sons, Inc.: Hoboken, NJ, 2013; pp 347−368. (6) Fürstner, A.; Shi, N. J. Am. Chem. Soc. 1996, 118, 12349. (7) For selected examples, see: (a) Bandini, M.; Cozzi, P. G.; Melchiorre, P.; Umani-Ronchi, A. Angew. Chem., Int. Ed. 1999, 38, 3357. (b) Berkessel, A.; Menche, D.; Sklorz, C. A.; Schröder, M.; Paterson, I. Angew. Chem., Int. Ed. 2003, 42, 1032. (c) Inoue, M.; Suzuki, T.; Nakada, M. J. Am. Chem. Soc. 2003, 125, 1140. (d) Wan, Z.-K.; Choi, H.-w.; Kang, F.-A.; Nakajima, K.; Demeke, D.; Kishi, Y. Org. Lett. 2002, 4, 4431. (e) Xiong, Y.; Zhang, G. J. Am. Chem. Soc. 2018, 140, 2735. (f) Xiong, Y.; Zhang, G. Org. Lett. 2016, 18, 5094. (8) For selected examples and reviews of C−H functionalization via photoredox catalysis, see: (a) Wang, C.-S.; Dixneuf, P. H.; Soulé, J.-F. Chem. Rev. 2018, 118, 7532. (b) Nakajima, K.; Miyake, Y.; Nishibayashi, Y. Acc. Chem. Res. 2016, 49, 1946. (c) Fabry, D. C.; Rueping, M. Acc. Chem. Res. 2016, 49, 1969. (d) Huang, L.; Rueping, M. Angew. Chem., Int. Ed. 2018, 57, 10333. (e) Loh, Y. Y.; Nagao, K.; Hoover, A. J.; Hesk, D.; Rivera, N. R.; Colletti, S. L.; Davies, I. W.; MacMillan, D. W. C. Science 2017, 358, 1182. (f) Le, C.; Liang, Y.; Evans, R. W.; Li, X.; MacMillan, D. W. C. Nature 2017, 547, 79. (g) Shaw, M. H.; Shurtleff, V. W.; Terrett, J. A.; Cuthbertson, J. D.; MacMillan, D. W. C. Science 2016, 352, 1304. (h) Jeffrey, J. L.; Terrett, J. A.; MacMillan, D. W. C. Science 2015, 349, 1532. (i) Romero, N. A.; Margrey, K. A.; Tay, N. E.; Nicewicz, D. A. Science 2015, 349, 1326. (j) McManus, J. B.; Nicewicz, D. A. J. Am. Chem.

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/jacs.8b08052. Experimental and computational details (PDF) Crystallographic Data for 6ca (CIF)

■

Communication

AUTHOR INFORMATION

Corresponding Author

*[email protected] ORCID

Frank Glorius: 0000-0002-0648-956X Author Contributions ‡

These authors contributed equally.

Notes

The authors declare no competing financial interest. 12708

DOI: 10.1021/jacs.8b08052 J. Am. Chem. Soc. 2018, 140, 12705−12709

Communication

Journal of the American Chemical Society Soc. 2017, 139, 2880. (k) Margrey, K. A.; Levens, A.; Nicewicz, D. A. Angew. Chem., Int. Ed. 2017, 56, 15644. (l) McManus, J. B.; Onuska, N. P. R.; Nicewicz, D. A. J. Am. Chem. Soc. 2018, 140, 9056. (m) Margrey, K. A.; Czaplyski, W. L.; Nicewicz, D. A.; Alexanian, E. J. J. Am. Chem. Soc. 2018, 140, 4213. (n) Mukherjee, S.; Maji, B.; Tlahuext-Aca, A.; Glorius, F. J. Am. Chem. Soc. 2016, 138, 16200. (9) For selected examples of intermolecular radical addition to formaldehyde, see: (a) Humphreys, R. W. R. J. Org. Chem. 1983, 48, 1483. (b) Sanderson, J. R.; Yeakey, E. L.; Lin, J. J.; Duranleau, R.; Marquis, E. T. J. Org. Chem. 1987, 52, 3243. (c) Sanderson, J. R.; Lin, J. J.; Duranleau, R. G.; Yeakey, E. L.; Marquis, E. T. J. Org. Chem. 1988, 53, 2859. (d) Oyama, M. J. Org. Chem. 1965, 30, 2429. (f) Kawamoto, T.; Fukuyama, T.; Ryu, I. J. Am. Chem. Soc. 2012, 134, 875. (10) For examples of intermolecular radical addition to carbonyls, see: (a) Pitzer, L.; Sandfort, F.; Strieth-Kalthoff, F.; Glorius, F. J. Am. Chem. Soc. 2017, 139, 13652. (b) Clerici, A.; Porta, O.; Zago, P. Tetrahedron 1986, 42, 561. (c) Clerici, A.; Porta, O. J. Org. Chem. 1989, 54, 3872. (11) (a) Wilsey, S.; Dowd, P.; Houk, K. N. J. Org. Chem. 1999, 64, 8801. (b) Curran, D. P.; Diederichsen, U.; Palovich, M. J. Am. Chem. Soc. 1997, 119, 4797. (c) Salamone, M.; Bietti, M. Synlett 2014, 25, 1803. (d) Hartung, J.; Gottwald, T.; Š pehar, K. Synthesis 2002, 1469. (12) For selected examples for radical coupling of alkyl radicals and ketyl radicals, see: (a) Fava, E.; Millet, A.; Nakajima, M.; Loescher, S.; Rueping, M. Angew. Chem., Int. Ed. 2016, 55, 6776. (b) Petronijević, F. R.; Nappi, M.; MacMillan, D. W. C. J. Am. Chem. Soc. 2013, 135, 18323. (c) Xia, Q.; Tian, H.; Dong, J.; Qu, Y.; Li, L.; Song, H.; Liu, Y.; Wang, Q. Chem. - Eur. J. 2018, 24, 9269. (13) Additionally, aldehydes can also be employed as acyl radical precursors in photoredox catalysis via hydrogen atom transfer. For selected examples, see: (a) Zhang, X.; MacMillan, D. W. C. J. Am. Chem. Soc. 2017, 139, 11353. (b) Mukherjee, S.; Garza-Sanchez, R. A.; Tlahuext-Aca, A.; Glorius, F. Angew. Chem., Int. Ed. 2017, 56, 14723. (c) Mukherjee, S.; Patra, T.; Glorius, F. ACS Catal. 2018, 8, 5842. (14) For selected reviews on the combination of photoredox and transition metal catalysis, see: (a) Twilton, J.; Le, C.; Zhang, P.; Shaw, M. H.; Evans, R. W.; MacMillan, D. W. C. Nat. Rev. Chem. 2017, 1, Article Number 0052. (b) Skubi, K. L.; Blum, T. R.; Yoon, T. P. Chem. Rev. 2016, 116, 10035. (c) Tellis, J. C.; Kelly, C. B.; Primer, D. N.; Jouffroy, M.; Patel, N. R.; Molander, G. A. Acc. Chem. Res. 2016, 49, 1429. (d) Tóth, B. L.; Tischler, O.; Novák, Z. Tetrahedron Lett. 2016, 57, 4505. (15) Lowry, M. S.; Goldsmith, J. I.; Slinker, J. D.; Rohl, R.; Pascal, R. A.; Malliaras, G. G.; Bernhard, S. Chem. Mater. 2005, 17, 5712. (16) (a) Hiyama, T.; Kimura, K.; Nozaki, H. Tetrahedron Lett. 1981, 22, 1037. (b) Wessjohann, L. A.; Scheid, G. Synthesis 1999, 1. (17) Another possible mechanism, involving oxidative quenching of the photocatalyst could not be ruled out. For details, see the Supporting Information. (18) For a discussion about the background reactivity, see the Supporting Information. (19) For selected examples of (enantioselective) carbonyl anti (αamino)allylation and anti (α-aryl)allylation, see: (a) Skucas, E.; Zbieg, J. R.; Krische, M. J. J. Am. Chem. Soc. 2009, 131, 5054. (b) Zbieg, J. R.; McInturff, E. L.; Krische, M. J. Org. Lett. 2010, 12, 2514. (c) Zhang, W.; Chen, W.; Xiao, H.; Krische, M. J. Org. Lett. 2017, 19, 4876. (d) Cabrera, J. M.; Tauber, J.; Zhang, W.; Xiang, M.; Krische, M. J. J. Am. Chem. Soc. 2018, 140, 9392. (20) CCDC 1858120 (6ac) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc. cam.ac.uk/data_request/cif. (21) Barros, J.; Serrani-Yarce, J. C.; Chen, F.; Baxter, D.; Venables, B. J.; Dixon, R. A. Nat. Plants 2016, 2, Article number 16050. (b) Vogt, T. Mol. Plant 2010, 3, 2. (22) Koike, T.; Akita, M. Inorg. Chem. Front. 2014, 1, 562.

(23) For selected reviews about 1,2-amino alcohols, see: (a) Bergmeier, S. C. Tetrahedron 2000, 56, 2561. (b) Ager, D. J.; Prakash, I.; Schaad, D. R. Chem. Rev. 1996, 96, 835. (24) (a) Gensch, T.; Teders, M.; Glorius, F. J. Org. Chem. 2017, 82, 9154. (b) Collins, K. D.; Glorius, F. Nat. Chem. 2013, 5, 597.

12709

DOI: 10.1021/jacs.8b08052 J. Am. Chem. Soc. 2018, 140, 12705−12709