E
S. Jung et al.
Letter
Synlett
um species F, releasing one mole of cyclopentene,20 which
synthesis of paracyclophanes, see: (e) Schomburg, D.;
Thielmann, M.; Winterfeldt, E. Tetrahedron Lett. 1985, 26, 1705.
(f) Bäurle, S.; Blume, T.; Mengel, A.; Parchmann, C.; Skuballa,
W.; Bäsler, S.; Schäfer, M.; Sülzle, D.; Wrona-Metzinger, H.-P.
Angew. Chem. Int. Ed. 2003, 42, 3961. (g) Krieger, J.-P.; Ricci, G.;
Lesuisse, D.; Meyer, C.; Cossy, J. Angew. Chem. Int. Ed. 2014, 53,
8705. For reviews associated with synthesis of planar chiral
cyclophanes, see: (h) Gulder, T.; Baran, P. S. Nat. Prod. Rep. 2012,
29, 899. (i) Kotha, S.; Shirbhate, M. E.; Waghule, G. T. Beilstein J.
Org. Chem. 2015, 11, 1274.
1
was, in fact, observed by direct H NMR monitoring of the
reaction.21
Intriguingly, a simpler substrate, but seemingly much
more difficult to attain the cyclization due to its conforma-
tional flexibility, saturated derivative 3122 was amenable to
smooth cyclization, giving 32 in 62% yield with a 21:1 ratio
of E/Z isomers,23 which indicates the styryl framework is
not necessary, at least at one side of the chains, for attaining
the stereoselective cyclization (Scheme 8).
(3) An elegant work for conformational and stereocontrolled syn-
thesis of cyclophane and its application for the total synthesis
of logithorone A, see: Layton, M. E.; Morales, C. A.; Shair, M. D.
J. Am. Chem. Soc. 2002, 124, 773.
(4) For syntheses of stereoselective carba-paracyclophanes, see:
(a) Kanomata, N.; Ochiai, Y. Tetrahedron Lett. 2001, 42, 1045.
(b) Ueda, T.; Kanomata, N.; Machida, H. Org. Lett. 2005, 7, 2365.
(c) Araki, T.; Noguchi, K.; Tanaka, K. Angew. Chem. Int. Ed. 2013,
52, 5617.
HO
HO
Grubbs I cat.
S+
S+
CH2Cl2
reflux, 1 h
O
O
(5) Mori, K.; Ohmori, K.; Suzuki, K. Angew. Chem. Int. Ed. 2009, 48,
5638.
O–
p-Tol
p-Tol
O–
H
H
31
32
(6) For references on the synthesis of paracyclophanes by ring-
closing olefin metathesis, see: (a) El-azizi, Y.; Schmitzer, A.;
Collins, S. K. Angew. Chem. Int. Ed. 2006, 45, 968. (b) Bolduc, P.;
Jacques, A.; Collins, S. K. J. Am. Chem. Soc. 2010, 132, 12790.
(c) Huang, M.; Song, L.; Liu, B. Org. Lett. 2010, 12, 2504.
(d) Setaka, W.; Higa, S.; Yamaguchi, K. Org. Biomol. Chem. 2014,
12, 3354; and references cited therein.
(7) After workup of the reaction, the crude material of 5 could also
be employed for the following coupling reaction with 10, giving
12 in 88% overall yield from 4.
62% (E/Z = 21:1)
Scheme 8 Ring-closing olefin metathesis of 31
In conclusion, we have demonstrated a modular syn-
thetic approach to unsymmetrical planar chiral carba-para-
cyclophanes by exploiting successive coupling of two dis-
tinct side chains.24 Construction of a single hydrogen-bond-
ing site is enough to control the planar stereochemistry of
the cyclized product. The strategy delineated herein could
prove useful for the future application for the synthesis of
related compounds including natural products.
(8) The five-step protocol with poor reproducibility as well as
expensive reagents and materials are serious shortcomings.
(9) Mikolajczyk, M.; Midura, W.; Grzejszczak, S.; Zatorski, A.;
Chefczynska, A. J. Org. Chem. 1978, 43, 473.
(10) Blanchette, M. A.; Choy, W.; Davis, J. T.; Essenfeld, A. P.;
Masamune, S.; Roush, W. R.; Sakai, T. Tetrahedron Lett. 1984, 25,
2183.
Acknowledgment
(11) Claus, R. E.; Schreiber, S. L. Org. Synth. 1986, 64, 150.
(12) For a further scope of this one-pot HWE reaction with 6, manu-
script in preparation.
This work was supported by a Grant-in-Aid for Specially Promoted
Research (No.23000006 and No.15K13690) from JSPS.
(13) The reaction with Pd(PPh3)4 in DMSO resulted in poor yield. In
use of K3PO4 as a base, the reaction provided only the homocou-
pling product in 24% yield.
(14) Ishiyama, T.; Murata, M.; Miyaura, N. J. Org. Chem. 1995, 60,
7508.
Supporting Information
Supporting information for this article is available online at
S
u
p
p
ortioInfgrmoaitn
S
u
p
p
ortiInfogrmoaitn
(15) For the syntheses of 22, 27, and 28, see the Supporting Informa-
tion.
References and Notes
(16) For hydrogen bond effects with sulfones, see: (a) Patai, S.;
Rappoport, Z.; Stirling, C. Sulphones and Sulphoxides; John Wiley
and Sons: Chichester, 1988, 561–562. (b) Laurence, C.; Brameld,
K. A.; Graton, J.; Le Questel, J.-Y.; Renault, E. J. Med. Chem. 2009,
52, 4073.
(1) (a) Hochmuth, D. H.; König, W. A. Tetrahedron: Asymmetry
1999, 10, 1089. (b) Gibson, S. E.; Knight, J. D. Org. Biomol. Chem.
2003, 1, 1256. (c) Rozenber, V.; Sergeeva, E.; Hopf, H. Modern
Cyclophane Chemistry; Gleiter, R.; Hopf, H., Eds.; Wiley-VCH:
New York, 2004, 435–462. (d) Elacqua, E.; MacGillivray, L. R. Eur.
J. Org. Chem. 2010, 6883. (e) Morisaki, Y.; Chujo, Y. Polym. Chem.
2011, 2, 1249.
(2) For references on enantioselective synthesis of paracyclo-
phanes, see: (a) Tanaka, K.; Hori, T.; Osaka, T.; Noguchi, K.;
Hirano, M. Org. Lett. 2007, 12, 4881. (b) Kanda, K.; Koike, T.;
Endo, K.; Shibata, T. Chem. Commun. 2009, 1870. (c) Kanda, K.;
Endo, K.; Shibata, T. Org. Lett. 2010, 9, 1980. (d) Araki, T.; Hojo,
D.; Noguchi, K.; Tanaka, K. Synlett 2011, 539. For stereoselective
(17) See the Supporting Information.
(18) Crystallographic data for compound 29·CHCl3 have been depos-
ited with the accession number CCDC 1415431, and can be
(19) Ring-closing olefin metathesis of 26 only gave undesired
product when second-generation Hoveyda–Grubbs catalyst was
used. See the Supporting Information for the details.
(20) Hoye, T. R.; Jeffrey, C. S.; Tennakoon, M. A.; Wang, J.; Zhao, H.
J. Am. Chem. Soc. 2004, 126, 10210.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F