Catalytic enantioselective intramolecular redox reactions: Ring-fused tetrahydroquinolines

Article abstract of DOI:10.1021/ja905213f

(Chemical Equation Presented) The first example of a catalytic enantioselective intramolecular hydride shift/ring closure reaction is reported. This redox neutral reaction cascade allows for the efficient formation of ring-fused tetrahydroquinolines in hi

Full text of DOI:10.1021/ja905213f

Published on Web 08/27/2009
Catalytic Enantioselective Intramolecular Redox Reactions: Ring-Fused
Tetrahydroquinolines
Sandip Murarka, Indubhusan Deb, Chen Zhang, and Daniel Seidel*
Department of Chemistry and Chemical Biology, Rutgers, The State UniVersity of New Jersey,
Piscataway, New Jersey 08854
Received June 24, 2009; E-mail: seidel@rutchem.rutgers.edu
Table 1. Evaluation of Reaction Parametersa
The functionalization of relatively unreactive C-H bonds via
intramolecular hydride shift/ring closure sequences offers intriguing
opportunities for the rapid buildup of molecular complexity (e.g., eq
1). Such transformations represent redox-neutral processes distinctly
different from oxidative C-H bond functionalizations.1,2 Exciting
advances in this field have recently been achieved by application of
catalytic approaches as a means of lowering activation barriers.3,4
However, a catalytic enantioselective variant of this process has
remained elusive. Here we report the first successful realization of such
a reaction in the context of tetrahydroquinoline synthesis (eq 2).5
entry
ligand
metal salt
time [h]
yield [%]b
dr [%]c
ee [%]d
1
2
3
4
6
6
6
7
7
8
8
8
8
8
8
8
8
9
9
Sc(OTf)3
Gd(OTf)3
Mg(ClO4)2 ·6H2O
Sc(OTf)3
48
48
72
48
48
12
12
48
72
72
12
12
30
48
48
12
72
72
15f
trace
trace
trace
trace
68
ND
ND
ND
ND
ND
19/ND
ND
ND
ND
ND
5
Gd(OTf)3
Reactions of the type outlined in eq 1 have been classified under
the term tert-amino effect.6,7 These transformations have been known
for some time and are typically promoted thermally. As part of a
program that focuses on the development of hydride shift processes,8
we have recently reported that gadolinium triflate efficiently catalyzes
the rearrangement of compounds 1 (Z, Z′ ) COR, COOR) to 3 at
room temperature.8c Unfortunately, attempts to develop a catalytic
enantioselective variant of this reaction have met with limited success.
Although thermally promoted rearrangements of compounds 1 typically
require the presence of two activating groups,9 we speculated that
Lewis acid catalysis could overcome this limitation. We thus decided
to investigate substrates bearing an acyl oxazolidinone (e.g., 4a) as an
alternative acceptor moiety capable of chelation to a chiral metal
complex.10 Initial attempts to promote rearrangement of readily
available 4a11 to 5a using scandium or gadolinium triflate in combina-
tion with ligand 6 or 7 led to disappointing results (Table 1, entries
1-5). Only trace formation of product 5a in low ee was observed in
one instance (entry 1). Gratifyingly, the use of nickel perchlorate in
combination with DBFox12 ligand 8 led to the formation of 5a in good
diastereo- and enantioselectivity (entry 6). In the absence of molecular
sieves, lower selectivities were observed (entry 7). The use of nickel
tetrafluoroborate or nickel hexafluoroantimonate led to inferior results
(entries 8 and 9). Whereas zinc perchlorate catalyzed the reaction less
efficiently (entry 10), magnesium salts in combination with ligand 8
led to excellent conversions (entries 11-13). The best result was
obtained with magnesium triflate (entry 13). While the diastereose-
lectivity in this case was slightly lower than that in the nickel
perchlorate catalyzed process, the overall yield and enantioselectivity
were improved. The use of DBFox ligand 9 or 10 in combination with
various nickel or magnesium salts led to no further improvement
(entries 14-17). It is important to note that 1,2-dichloroethane is
uniquely effective as a solvent.13 No or very sluggish product formation
was observed when performing the reaction at temperatures lower than
84 °C (reflux).
6
Ni(ClO4)2 ·6H2O
Ni(ClO4)2 ·6H2O
Ni(BF4)2 ·6H2O
Ni(SbF6)2
Zn(ClO4)2 ·6H2O
Mg(ClO4)2 ·6H2O
Mg(NTf2)2
Mg(OTf)2
Ni(ClO4)2 ·6H2O
Mg(OTf)2
89:11 90/85
83:17 89/81
88:12 83/85
ND
ND
75:25 87/91
81:19 77/77
74:26 94/85
ND
ND
7e
8
70
68
9
28f
30f
89
71/ND
58/ND
10
11
12
13
14
15
16
17
18g
75
88
29f
18f
80
54/ND
44/ND
10
10
8
Ni(ClO4)2 ·6H2O
Mg(OTf)2
Mg(OTf)2
81:19 75/73
ND 45/ND
70:30 61/60
35f
50
a Reactions were performed on a 0.12 mmol scale. The ee’s were
determined by HPLC analysis. b Combined yield of both diastereomers.
c Determined by 1H NMR. d Major/minor diastereomer. e Reaction
performed without molecular sieves. f Isolated yield of major
diastereomer, reaction did not proceed to completion. g Reaction
performed in CH3NO2.
Using the optimized conditions, the scope of the reaction was
explored (Chart 1). Various substitution patterns on the basic substrate
framework are well tolerated (products 5a-e). Starting materials
derived from ꢀ-carboline and N-Me-ꢀ-carboline underwent the rear-
rangement successfully and gave rise to products 5f and 5g in good
yields and high levels of stereoselectivity. Products 5h and 5i which
incorporate seven- or eight-membered azacycles were formed in good
yields but with reduced levels of enantio- and diastereoselectivity.
The absolute configuration of products 5b and 5e was determined
by X-ray crystallographic analysis.11 Figure 1 shows a proposed
transition state that accounts for the formation of the major product
enantiomer. Formation of the opposite enantiomer would suffer from
severe interactions between the substrate and the phenyl residue of
the ligand, a fact that helps to explain the observed high levels of
enantioselectivity at this relatively high reaction temperature. The
9
13226 J. AM. CHEM. SOC. 2009, 131, 13226–13227
10.1021/ja905213f CCC: $40.75  2009 American Chemical Society

C O M M U N I C A T I O N S
Chart 1. Scope of the Reactiona b
,
Acknowledgment. We thank the National Science Foundation
for support of this research (Grant CHE-0911192). Startup support
from Rutgers, The State University of New Jersey is gratefully
acknowledged. We thank Dr. Tom Emge for crystallographic analysis.
Supporting Information Available: Additional discussion, experi-
mental procedures, and characterization data including X-ray crystal
structures of 5b and 5e. This material is available free of charge via the
Internet at http://pubs.acs.org.
References
(1) For reviews on C-H bond functionalizations, see:(a) Godula, K.; Sames,
D. Science 2006, 312, 67. (b) Dick, A. R.; Sanford, M. S. Tetrahedron
2006, 62, 2439. (c) Davies, H. M. L. Angew. Chem., Int. Ed. 2006, 45,
6422. (d) Alberico, D.; Scott, M. E.; Lautens, M. Chem. ReV. 2007, 107,
174. (e) Bergman, R. G. Nature 2007, 446, 391. (f) Davies, H. M. L.;
Manning, J. R. Nature 2008, 451, 417. (g) Thansandote, P.; Lautens, M.
Chem.sEur. J. 2009, 15, 5874. (h) Li, C.-J. Acc. Chem. Res. 2009, 42,
335.
(2) For an excellent review on the functionalization of sp3 C-H bonds adjacent
to nitrogen in heterocycles, see:Campos, K. R. Chem. Soc. ReV. 2007, 36,
1069.
(3) (a) Pastine, S. J.; McQuaid, K. M.; Sames, D. J. Am. Chem. Soc. 2005,
127, 12180. (b) Pastine, S. J.; Sames, D. Org. Lett. 2005, 7, 5429. (c)
Tobisu, M.; Chatani, N. Angew. Chem., Int. Ed. 2006, 45, 1683. (d)
McQuaid, K. M.; Sames, D. J. Am. Chem. Soc. 2009, 131, 402. (e) Shikanai,
D.; Murase, H.; Hata, T.; Urabe, H. J. Am. Chem. Soc. 2009, 131, 3166.
(f) Mahoney, S. J.; Moon, D. T.; Hollinger, J.; Fillion, E. Tetrahedron
Lett. 2009, 50, 4706. (g) McQuaid, K. M.; Long, J. Z.; Sames, D. Org.
Lett. 2009, 11, 2972. (h) Mori, K.; Ohshima, Y.; Ehara, K.; Akiyama, T.
Chem. Lett. 2009, 38, 524.
a Reactions were performed on a 0.3 mmol scale. The ee’s were
determined by HPLC analysis, and dr’s by 1H NMR. b Ni(ClO4)2 ·6H2O
was used instead of Mg(OTf)2.
(4) For selected examples of 1,5-hydride shift processes in nonconjugated
systems, see:(a) Woodward, R. B.; Sondheimer, F.; Mazur, Y. J. Am. Chem.
Soc. 1958, 80, 6693. (b) Ten Broeke, J.; Douglas, A. W.; Grabowski, E. J. J.
J. Org. Chem. 1976, 41, 3159. (c) Heathcock, C. H. Proc. Natl. Acad. Sci.
U.S.A. 1996, 93, 14323. (d) Woelfling, J.; Frank, E.; Schneider, G.; Tietze,
L. F. Eur. J. Org. Chem. 2004, 90. (e) Cui, L.; Peng, Y.; Zhang, L. J. Am.
Chem. Soc. 2009, 131, 8394.
(5) For a review on the synthesis of tetrahydroquinolines, see:Katritzky, A. R.;
Rachwal, S.; Rachwal, B. Tetrahedron 1996, 52, 15031.
(6) For reviews, see:(a) Meth-Cohn, O.; Suschitzky, H. AdV. Heterocycl. Chem.
1972, 14, 211. (b) Verboom, W.; Reinhoudt, D. N. Recl. TraV. Chim. Pays-
Bas 1990, 109, 311. (c) Meth-Cohn, O. AdV. Heterocycl. Chem. 1996, 65,
1. (d) Quintela, J. M. Recent Res. DeV. Org. Chem. 2003, 7, 259. (e) Matyus,
P.; Elias, O.; Tapolcsanyi, P.; Polonka-Balint, A.; Halasz-Dajka, B. Synthesis
2006, 2625.
(7) For selected examples, see:(a) Verboom, W.; Reinhoudt, D. N.; Visser,
R.; Harkema, S. J. Org. Chem. 1984, 49, 269. (b) Nijhuis, W. H. N.;
Verboom, W.; Reinhoudt, D. N.; Harkema, S. J. Am. Chem. Soc. 1987,
109, 3136. (c) Nijhuis, W. H. N.; Verboom, W.; Abu El-Fadl, A.; Harkema,
S.; Reinhoudt, D. N. J. Org. Chem. 1989, 54, 199. (d) Nijhuis, W. H. N.;
Verboom, W.; Abu El-Fadl, A.; Van Hummel, G. J.; Reinhoudt, D. N. J.
Org. Chem. 1989, 54, 209. (e) De Boeck, B.; Jiang, S.; Janousek, Z.; Viehe,
H. G. Tetrahedron 1994, 50, 7075. (f) De Boeck, B.; Janousek, Z.; Viehe,
H. G. Tetrahedron 1995, 51, 13239. (g) Ojea, V.; Muinelo, I.; Quintela,
J. M. Tetrahedron 1998, 54, 927. (h) Kaval, N.; Halasz-Dajka, B.; Vo-
Thanh, G.; Dehaen, W.; Van der Eycken, J.; Matyus, P.; Loupy, A.; Van
der Eycken, E. Tetrahedron 2005, 61, 9052. (i) Ruble, J. C.; Hurd, A. R.;
Johnson, T. A.; Sherry, D. A.; Barbachyn, M. R.; Toogood, P. L.; Bundy,
G. L.; Graber, D. R.; Kamilar, G. M. J. Am. Chem. Soc. 2009, 131, 3991.
(8) (a) Zhang, C.; De, C. K.; Mal, R.; Seidel, D. J. Am. Chem. Soc. 2008, 130,
416. (b) Zhang, C.; Murarka, S.; Seidel, D. J. Org. Chem. 2009, 74, 419.
(c) Murarka, S.; Zhang, C.; Konieczynska, M. D.; Seidel, D. Org. Lett.
2009, 11, 129.
Figure 1. Proposed transition state leading to major diastereomer. Absolute
configuration of 5b (X-ray).
proposed trigonal bipyramidal coordination geometry for the magne-
sium DBFox complex has previously been suggested by Kanemasa
et al.12d
The absolute configuration of the minor diastereomer 5a′ was
determined as outlined in eq 4. Upon exposure to DBU, partial
equilibration to the major diastereomer 5a with slight erosion of ee
was observed. Compound 5a was recovered as the same enantiomer
(R,R) that is formed in the catalytic reaction as revealed by HPLC
correlation.11 This established the absolute configuration of 5a′ as
shown.14
(9) A single nitro group has been shown to be sufficient for activation under
thermal conditions:Rabong, C.; Hametner, C.; Mereiter, K.; Kartsev, V. G.;
Jordis, U. Heterocycles 2008, 75, 799.
(10) For examples of using acyl oxazolidinones as achiral templates, see:(a)
Narasaka, K.; Inoue, M.; Okada, N. Chem. Lett. 1986, 1109. (b) Johnson,
J. S.; Evans, D. A. Acc. Chem. Res. 2000, 33, 325. (c) Evans, D. A.; Scheidt,
K. A.; Johnston, J. N.; Willis, M. C. J. Am. Chem. Soc. 2001, 123, 4480.
(d) Desimoni, G.; Faita, G.; Jorgensen, K. A. Chem. ReV. 2006, 106, 3561.
(e) Reymond, S.; Cossy, J. Chem. ReV. 2008, 108, 5359.
(11) See the Supporting Information for details.
(12) (a) Kanemasa, S.; Oderaotoshi, Y.; Yamamoto, H.; Tanaka, J.; Wada, E.;
Curran, D. P. J. Org. Chem. 1997, 62, 6454. (b) Kanemasa, S.; Oderaotoshi,
Y.; Sakaguchi, S.-i.; Yamamoto, H.; Tanaka, J.; Wada, E.; Curran, D. P.
J. Am. Chem. Soc. 1998, 120, 3074. (c) Iserloh, U.; Curran, D. P.;
Kanemasa, S. Tetrahedron: Asymmetry 1999, 10, 2417. (d) Kanemasa, S.;
Kanai, T. J. Am. Chem. Soc. 2000, 122, 10710.
(13) Reactions performed in toluene, trifluorotoluene, chloroform, dichlo-
romethane, or acetonitrile (all at reflux temperature) led to no formation of
product.
(14) For additional experiments regarding the interconversion between 5a and
5a′ under the reaction conditions, see the Supporting Information.
In summary, we have described the first example of a catalytic
enantioselective hydride shift/ring closure reaction cascade. Ring-fused
tetrahydroquinolines are obtained in good yields and with high levels
of enantioselectivity. It is anticipated that this communication will set
the stage for a variety of other catalytic enantioselective processes
involving hydride shift triggered reaction cascades.
JA905213F
9
J. AM. CHEM. SOC. VOL. 131, NO. 37, 2009 13227