Letter pubs.acs.org/OrgLett
Organocatalytic Approach for C(sp3)−H Bond Arylation, Alkylation, and Amidation of Isochromans under Facile Conditions Wataru Muramatsu* and Kimihiro Nakano Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki, Nagasaki 852-8521, Japan S Supporting Information *
ABSTRACT: A new catalytic approach for the synthesis of isochroman derivatives via direct C(sp3)−H bond arylation is described. The oxidation reaction with [bis(trifluoroacetoxy)iodo]benzene facilitates the regeneration of 2,3-dichloro-5,6dicyano-1,4-benzoquinone in the C(sp3)−H bond arylation of isochroman. The reaction conditions can also be used for alkyl Grignard reagents and amides to afford the corresponding isochroman derivatives.
W
Scheme 1. General Methods for C(sp3)−H Bond Arylation of Isochromans
ith the rapid development of synthetic organic chemistry over the past few decades, significant progress has been made in carrying out very difficult chemical reactions, in particular, C−H bond activation reactions such as crossdehydrogenative-coupling (CDC) reactions.1 We are primarily interested in investigating the activation of the inert C(sp3)−H bond of benzyl ethers such as isochroman. Because isochroman derivatives exhibit various potential bioactivities2 and may serve as important building blocks in drug development in the future, the C−H bond activation reaction has attracted attention as one of the most efficient synthetic methods. Studies on the direct C(sp3)−C(sp3) and C(sp3)−C(sp) bond formations at the C(1) position of isochroman via C(sp3)−H bond activation have been widely reported.3 Additionally, in recent years, Liu and co-workers have also reported a one-pot enantioselective C(sp3)−C(sp3) bond formation with a chiral organocatalyst.4 On the other hand, only a few methods for the catalytic and noncatalytic C(sp3)−H bond arylation at the C(1) position of isochroman have been reported by four research groups.5 Schnürch and co-workers first developed the catalytic system by employing 5.0 mol % of Fe(NO3)3·9H2O and 1.3 equiv of TBHP as the oxidant in 2010 (eq 1 of Scheme 1).5a,b Todd and co-workers utilized 10 mol % of CuCl2 and 1.1 equiv of 2,3dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as the oxidant in 2012 (eq 2 of Scheme 1).5c MacMillan and co-workers succeeded in the C(sp3)−H bond arylation of isochroman via photoredox catalysis in 2014 (eq 3 of Scheme 1).5e Recently, we reported that the desired coupled products with an aryl group at the C(1) position of isochroman could be obtained in 77−91% yields when isochroman was oxidized with 1.1 equiv of DDQ, followed by treatment with ArMgBr/Et2O (eq 4 of Scheme 1).5d Our method can be considered as an inexpensive, effective, and highly versatile reaction because it not only affords the desired coupling products in a short period under mild reaction conditions but also does not require expensive heavy-metal catalysts. However, because a stoichiometric amount of DDQ is needed, its toxicity should be considered.6 Herein we report the first organocatalytic method with high © 2014 American Chemical Society
efficiency and functional compatibility for the direct C(sp3)−H bond arylation of isochroman (eq 5 of Scheme 1), and application of the method to C(sp3)−H bond alkylation and amidation. Listed in Table 1 is some information about variations from “standard” conditions for the catalytic C(sp3)−H bond Received: February 28, 2014 Published: March 27, 2014 2042
dx.doi.org/10.1021/ol5006399 | Org. Lett. 2014, 16, 2042−2045
Organic Letters
Letter
Table 1. DDQ-Catalyzed C(sp3)−H Bond Arylation of Isochroman
entry
variation from the “standard” conditions
yield of 1 (%)a
1 2 3 4 5 6 7 8 9c 10c 11c 12c 13c 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30d 31e 32d 33d 34 35 36
none no DDQ no PIFA MnO2, instead of PIFA Mn(OAc)3, instead of PIFA HCl/EtOH, PbO2, instead of PIFA HNO3, instead of PIFA N2O4/DCE instead of PIFA addition of NaHCO3 (2.0 equiv) addition of Na2CO3 (2.0 equiv) addition of K2CO3 (2.0 equiv) addition of pyridine (2.0 equiv) addition of 2,4,6-collidine (2.0 equiv) chloranil, instead of DDQ o-chloronil, instead of DDQ PIDA, instead of PIFA PFPIFA, instead of PIFA C3F7(Ph)IOTf, instead of PIFA PhMgI/Et2O (1.0 M), instead of 2.0 M PhMgCl/Et2O, instead of PhMgBr/Et2O PhMgBr/Et2O, instead of PhMgI/Et2O PhMgI/THF, instead of PhMgI/Et2O PhMgBr/THF, instead of PhMgI/Et2O PhZnBr/Et2O, instead of PhMgI/Et2O PhZnI/Et2O, instead of PhMgI/Et2O Ph2Zn, instead of PhMgI/Et2O PhLi/Bu2O, instead of PhMgI/Et2O PhCl, instead of DCE PhMe, instead of DCE 1,1-DCE, instead of DCE DBE, instead of DCE THF, instead of DCE Et2O, instead of DCE CPME, instead of DCE MeCN, instead of DCE DMF, instead of DCE
86 (84)b
Organocatalytic Approach for C(sp3)−H Bond Arylation, Alkylation, and Amidation of Isochromans under Facile Conditions Wataru Muramatsu* and Kimihiro Nakano Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki, Nagasaki 852-8521, Japan S Supporting Information *
ABSTRACT: A new catalytic approach for the synthesis of isochroman derivatives via direct C(sp3)−H bond arylation is described. The oxidation reaction with [bis(trifluoroacetoxy)iodo]benzene facilitates the regeneration of 2,3-dichloro-5,6dicyano-1,4-benzoquinone in the C(sp3)−H bond arylation of isochroman. The reaction conditions can also be used for alkyl Grignard reagents and amides to afford the corresponding isochroman derivatives.
W
Scheme 1. General Methods for C(sp3)−H Bond Arylation of Isochromans
ith the rapid development of synthetic organic chemistry over the past few decades, significant progress has been made in carrying out very difficult chemical reactions, in particular, C−H bond activation reactions such as crossdehydrogenative-coupling (CDC) reactions.1 We are primarily interested in investigating the activation of the inert C(sp3)−H bond of benzyl ethers such as isochroman. Because isochroman derivatives exhibit various potential bioactivities2 and may serve as important building blocks in drug development in the future, the C−H bond activation reaction has attracted attention as one of the most efficient synthetic methods. Studies on the direct C(sp3)−C(sp3) and C(sp3)−C(sp) bond formations at the C(1) position of isochroman via C(sp3)−H bond activation have been widely reported.3 Additionally, in recent years, Liu and co-workers have also reported a one-pot enantioselective C(sp3)−C(sp3) bond formation with a chiral organocatalyst.4 On the other hand, only a few methods for the catalytic and noncatalytic C(sp3)−H bond arylation at the C(1) position of isochroman have been reported by four research groups.5 Schnürch and co-workers first developed the catalytic system by employing 5.0 mol % of Fe(NO3)3·9H2O and 1.3 equiv of TBHP as the oxidant in 2010 (eq 1 of Scheme 1).5a,b Todd and co-workers utilized 10 mol % of CuCl2 and 1.1 equiv of 2,3dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as the oxidant in 2012 (eq 2 of Scheme 1).5c MacMillan and co-workers succeeded in the C(sp3)−H bond arylation of isochroman via photoredox catalysis in 2014 (eq 3 of Scheme 1).5e Recently, we reported that the desired coupled products with an aryl group at the C(1) position of isochroman could be obtained in 77−91% yields when isochroman was oxidized with 1.1 equiv of DDQ, followed by treatment with ArMgBr/Et2O (eq 4 of Scheme 1).5d Our method can be considered as an inexpensive, effective, and highly versatile reaction because it not only affords the desired coupling products in a short period under mild reaction conditions but also does not require expensive heavy-metal catalysts. However, because a stoichiometric amount of DDQ is needed, its toxicity should be considered.6 Herein we report the first organocatalytic method with high © 2014 American Chemical Society
efficiency and functional compatibility for the direct C(sp3)−H bond arylation of isochroman (eq 5 of Scheme 1), and application of the method to C(sp3)−H bond alkylation and amidation. Listed in Table 1 is some information about variations from “standard” conditions for the catalytic C(sp3)−H bond Received: February 28, 2014 Published: March 27, 2014 2042
dx.doi.org/10.1021/ol5006399 | Org. Lett. 2014, 16, 2042−2045
Organic Letters
Letter
Table 1. DDQ-Catalyzed C(sp3)−H Bond Arylation of Isochroman
entry
variation from the “standard” conditions
yield of 1 (%)a
1 2 3 4 5 6 7 8 9c 10c 11c 12c 13c 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30d 31e 32d 33d 34 35 36
none no DDQ no PIFA MnO2, instead of PIFA Mn(OAc)3, instead of PIFA HCl/EtOH, PbO2, instead of PIFA HNO3, instead of PIFA N2O4/DCE instead of PIFA addition of NaHCO3 (2.0 equiv) addition of Na2CO3 (2.0 equiv) addition of K2CO3 (2.0 equiv) addition of pyridine (2.0 equiv) addition of 2,4,6-collidine (2.0 equiv) chloranil, instead of DDQ o-chloronil, instead of DDQ PIDA, instead of PIFA PFPIFA, instead of PIFA C3F7(Ph)IOTf, instead of PIFA PhMgI/Et2O (1.0 M), instead of 2.0 M PhMgCl/Et2O, instead of PhMgBr/Et2O PhMgBr/Et2O, instead of PhMgI/Et2O PhMgI/THF, instead of PhMgI/Et2O PhMgBr/THF, instead of PhMgI/Et2O PhZnBr/Et2O, instead of PhMgI/Et2O PhZnI/Et2O, instead of PhMgI/Et2O Ph2Zn, instead of PhMgI/Et2O PhLi/Bu2O, instead of PhMgI/Et2O PhCl, instead of DCE PhMe, instead of DCE 1,1-DCE, instead of DCE DBE, instead of DCE THF, instead of DCE Et2O, instead of DCE CPME, instead of DCE MeCN, instead of DCE DMF, instead of DCE
86 (84)b
