Organic Letters
Letter
(5) Tellis, J. C.; Primer, D. N.; Molander, G. A. Science 2014, 345,
433.
(6) Primer, D. N.; Karakaya, I.; Tellis, J. C.; Molander, G. A. J. Am.
Chem. Soc. 2015, 137, 2195.
(7) Jana, R.; Pathak, T. P.; Sigman, M. S. Chem. Rev. 2011, 111, 1417.
(8) Breitenfeld, J.; Ruiz, J.; Wodrich, M. D.; Hu, X. J. Am. Chem. Soc.
2013, 135, 12004.
(9) Han, C.; Buchwald, S. L. J. Am. Chem. Soc. 2009, 7532.
(10) Pompeo, M.; Froese, R. D. J.; Hadei, N.; Organ, M. G. Angew.
Chem., Int. Ed. 2012, 51, 11354.
oxidation to afford a mixture of alcohol, aldehyde, and other
oxidation byproducts.39,40 Consequently, a method for the
preparation of protected benzylic alcohol variants from the far
more widely available aryl and heteroaryl halides serves as an
attractive method for reliable synthesis and long-term storage.
To that end, allyl-, para-methoxybenzyl-, tert-butyl-, and
trimethylsilylethyl-protected α-alkoxymethyltrifluoroborates
were synthesized and employed as cross-coupling partners to
give products 53−56. Subsequent deprotection of these
protected alcohols allows the formation of benzylic alcohols
in two steps from readily accessible bromoarenes.
In summary, room-temperature conditions for the cross-
coupling of α-alkoxymethyltrifluoroborates with an array of aryl
bromides has been communicated. Previous reports for the
cross-coupling of these substrates with aryl chlorides have taken
place at 100 °C in the presence of a strong aqueous base and
have suffered from significant limitations in scope when applied
to both heteroaryl chlorides and -bromides. Consequently, the
developed couplings address key substrate limitations of the
former methods. Furthermore, the delineated procedures
provide a method for the synthesis of benzylic ethers that
can be readily deprotected to afford the corresponding alcohols,
many of which are challenging to access in high purity.
́
(11) Vila, C.; Giannerini, M.; Hornillos, V.; Fananas-Mastral, M.;
̃
Feringa, B. L. Chem. Sci. 2014, 5, 1361.
(12) Dreher, S. D.; Dormer, P. G.; Sandrock, D. L.; Molander, G. A.
J. Am. Chem. Soc. 2008, 130, 9257.
(13) Li, L.; Zhao, S.; Joshi-Pangu, A.; Diane, M.; Biscoe, M. R. J. Am.
Chem. Soc. 2014, 136, 14027.
(14) Noble, A.; McCarver, S. J.; MacMillan, D. W. C. J. Am. Chem.
Soc. 2015, 137, 624.
(15) Zuo, Z.; Ahneman, D.; Chu, L.; Terrett, J.; Doyle, A. G.;
MacMillan, D. W. C. Science 2014, 345, 437.
(16) Zhang, S.-Y.; Zhang, F.-M.; Tu, Y.-Q. Chem. Soc. Rev. 2011, 40,
1937.
(17) Molander, G. A.; Colombel, V.; Braz, V. A. Org. Lett. 2011, 13,
1852.
(18) Yasu, Y.; Koike, T.; Akita, M. Adv. Synth. Catal. 2012, 354, 3414.
(19) Miyazawa, K.; Yasu, Y.; Koike, T.; Akita, M. Chem. Commun.
2013, 49, 7249.
(20) Lawrence, N. J.; Rennison, D.; Woo, M.; McGown, A. T.;
Hadfield, J. A. Bioorg. Med. Chem. Lett. 2001, 11, 51.
(21) Thompson, A. M.; Blaser, A.; Anderson, R. F.; Shinde, S. S.;
Franzblau, S. G.; Ma, Z.; Denny, W. A.; Palmer, B. D. J. Med. Chem.
2009, 52, 637.
Finally, although the products derived from these reactions
can often be made by other means, the use of these reagents
serves to validate further the photoredox cross-coupling
3
manifold as a means of engaging Csp nucleophiles in alkyl
transfer under mild conditions. Most importantly, the ability to
cross-couple late stage bromides with an ever-expanding library
3
of Csp hybridized nucleophiles using a single robust catalyst
(22) Guven, O. O.; Erdog
Chem. Lett. 2007, 17, 2233.
an, T.; Goker, H.; Yildiz, S. Bioorg. Med.
̈
̈
system is anticipated to enable practitioners to diversify their
synthetic molecular architecture quickly and expand three-
dimensional chemical space.41
(23) Helms, B.; Mynar, J. L.; Hawker, C. J.; Frec
Chem. Soc. 2004, 126, 15020.
́
het, J. M. J. J. Am.
(24) Percec, V.; Heck, J.; Lee, M.; Ungar, G.; Alvarez-Castillo, A. J.
Mater. Chem. 1992, 2, 1033.
(25) Hutchinson, D. K.; Fuchs, P. L. J. Am. Chem. Soc. 1987, 109,
ASSOCIATED CONTENT
■
S
4930.
* Supporting Information
(26) Tamao, K.; Ishida, N.; Ito, Y.; Makoto, K. Org. Synth. 1990, 69,
96.
(27) Blanc, R.; Groll, K.; Bernhardt, S.; Stockmann, P.; Knochel, P.
Synthesis 2014, 46, 1052.
Experimental procedures and spectra data. The Supporting
(28) Sakata, K.; Urabe, D.; Inoue, M. Tetrahedron Lett. 2013, 54,
4189.
(29) Masanori, K.; Takashi, S.; Toshimi, O.; Hiroshi, S.; Toshihiko,
M. Chem. Lett. 1984, 1225.
(30) Majeed, A. J.; Antonsen, O.; Benneche, T.; Undheim, K.
Tetrahedron 1989, 45, 993.
AUTHOR INFORMATION
■
Corresponding Author
Notes
(31) Falck, J. R.; Patel, P. K.; Bandyopadhyay, A. J. Am. Chem. Soc.
2007, 129, 790.
The authors declare no competing financial interest.
(32) Goli, M.; He, A.; Falck, J. R. Org. Lett. 2011, 13, 344.
(33) Molander, G. A.; Canturk, B. Org. Lett. 2008, 10, 2135.
(34) Murai, N.; Yonaga, M.; Tanaka, K. Org. Lett. 2012, 14, 1278.
(35) Koike, T.; Akita, M. Inorg. Chem. Front. 2014, 1, 562.
(36) Gutierrez, O.; Tellis, J. C.; Primer, D. N.; Molander, G. A.;
Kozlowski, M. C. J. Am. Chem. Soc. 2015, 137, 4896.
(37) Wang, A.; Yang, Z.; Liu, J.; Gui, Q.; Chen, X.; Tan, Z.; Shi, J.-C.
Synth. Commun. 2014, 44, 280.
(38) Harris, J. M.; Chess, R. B. Nat. Rev. Drug Discovery 2003, 2, 214.
(39) Urakami, K.; Kobayashi, C.; Miyazaki, Y.; Nishijima, K.;
Yoshimura, Y.; Hashimoto, K. Chem. Pharm. Bull. 2000, 48, 1299.
(40) Abend, A. M.; Chung, L.; Bibart, R. T.; Brooks, M.; McCollum,
D. G. J. Pharm. Biomed. Anal. 2004, 34, 957.
ACKNOWLEDGMENTS
■
This research was generously supported by the National
Institute of General Medical Sciences (R01-GM113878) and
̈
̇
TUBITAK. We thank Frontier Scientific for providing several
organoboron reagents used in this research and Aldrich for
iridium salts used in the preparation of the photoredox
catalysts.
REFERENCES
■
(1) Tucker, J. W.; Stephenson, C. R. J. J. Org. Chem. 2012, 77, 1617.
(2) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 2013,
113, 5322.
(41) Lovering, F.; Bikker, J.; Humblet, C. J. Med. Chem. 2009, 52,
6752.
(3) Hopkinson, M. N.; Sahoo, B.; Li, J.-L.; Glorius, F. Chem.Eur. J.
2014, 20, 3874.
(4) Lloyd-Jones, G. C.; Ball, L. T. Science 2014, 345, 381.
D
Org. Lett. XXXX, XXX, XXX−XXX