Table
2
Modular and exclusive synthesis of 3,4-disubstituted or
an unexpected oxidative rearrangement of arylalkenes, which
is surprisingly assisted by the use of excess water and micro-
wave irradiation under neutral conditions.
2-bromo-4,5-disubstituted arylaldehydes using varying amounts of NBSa
Equiv.
NBS
used
Although this methodology provided a modest ee in these
initial investigations, it offers a promising platform for the
hitherto unknown organocatalytic enantioselective oxidation
of arylalkenes. Further studies to improve the scope and
enantioselectivity of this transformation using various other
chiral catalysts are currently under way in our laboratory.
A. S., N. S., R. K. and U. K. S. are indebted to C.S.I.R,
New Delhi, for the award of research fellowships. We are
thankful to Dr R. S. Jolly (IMTECH, Chandigarh) for
discussions regarding europium shift NMR experiments. The
authors gratefully acknowledge financial assistance from
project MLP-0025, as well as the Director of I.H.B.T.,
Palampur for his kind cooperation and encouragement.
Compound
Entry number
Substrate
Yield (%)b
1
11
1
11b
(60%)
4
1
4
11b0
(68%)
2
12
12b
(52%)
12b0
(69%)
a
General conditions: substrate (entries 1 and 2, 0.96 mmol), CTAB
Notes and references
(20 mol%), NBS (1 equiv. or 4 equiv.), water (11 ml) and DMSO (3.7 ml)
under MW for 15 min (250 W, 115 1C). The structure of all the novel
compounds was confirmed by NMR (1H, 13C) and HRMS analysis
1 For pertinent reviews on organic synthesis in water, see: (a) C. J. Li
and L. Chen, Chem. Soc. Rev., 2006, 35, 68; (b) D. Dallinger and
C. O. Kappe, Chem. Rev., 2007, 107, 2563; (c) A representative
example: A. Sharma, R. Kumar, N. Sharma, V. Kumar and
A. K. Sinha, Adv. Synth. Catal., 2008, 350, 2910.
b
(see the ESI for details). Yield of pure isolated product (single run).
2 (a) J. Barluenga, M. M. Arias, F. G. Bobes, A. Ballesteros and
J. M. Gonzalez, Chem. Commun., 2004, 2616; (b) M. F. A. Adamo,
V. K. Aggarwal and M. A. Sage, J. Am. Chem. Soc., 2000, 122, 8317.
3 (a) J. J. Kim and H. Alper, Chem. Commun., 2005, 3059; (b) Y. Yan
and X. Zhang, J. Am. Chem. Soc., 2006, 128, 7198.
4 (a) C. A. Dvorak, US Pat., 4395571, 1983; (b) J. K. Stille and
G. Parrinello, Eur. Pat., 314759, 1989.
5 G. R. Pettit, J. W. Lippert and D. L. Herald, J. Org. Chem., 2000,
65, 7438.
6 (a) T. Baumann, M. Bachle and S. Brase, Org. Lett., 2006, 8, 3797;
(b) S. Brase, T. Baumann, S. Dahmenb and H. Vogt, Chem.
Commun., 2007, 1881.
Scheme 2 Organocatalytic enantioselective oxidation.
7 (a) A. Padwa, M. D. Danca, K. I. Hardcastle and M. S. McClure,
J. Org. Chem., 2003, 68, 929; (b) R. Martin and S. L. Buchwald,
Angew. Chem., Int. Ed., 2007, 46, 7236.
8 (a) R. Sudha, K. M. Narasimhan, V. G. Saraswathy and
S. Sankararaman, J. Org. Chem., 1996, 61, 1877; (b) S. Kulasegaram
and R. J. Kulawiec, J. Org. Chem., 1997, 62, 6547; (c) B. C. Ranu and
U. Jana, J. Org. Chem., 1998, 63, 8212; (d) K. Suda, S. Nakajima,
Y. Satoh and T. Takanami, Chem. Commun., 2009, 1255; (e) M. W. C.
Robinson, A. M. Davies, R. Buckle, I. Mabbett, S. H. Taylor and
A. E. Graham, Org. Biomol. Chem., 2009, 7, 2559.
In view of the rearrangement-type mechanistic rationale
(Fig. 1), we were eager to see if the use of Cinchona-based chiral
phase transfer organocatalysts18 could provide an asymmetric
version of the water-promoted oxidative rearrangement of
arylalkenes. As a proof of concept, 11a was treated with NBS
(1.3 equiv.) using water–DMSO (3 : 1 ratio) in the presence of
(ꢀ)-N-benzyl-cinchonidinium chloride (19, 20 mol%) to provide
corresponding 11b in 50% yield (Scheme 2). However, our
subsequent attempts to ascertain the enantiomeric excess (ee)
proved futile as 11b proved to be non-resolvable under both
chiral GC and HPLC conditions, which was further corro-
borated by a couple of literature precedents.3b,4b At this stage,
9 G. Jiang, J. Chen, H. Y. Thu, J. S. Huang, N. Zhu and C. M. Che,
Angew. Chem., Int. Ed., 2008, 47, 6638.
10 (a) D. R. Dalton, V. P. Dutta and D. C. Jones, J. Am. Chem. Soc.,
1968, 90, 5498; (b) J. Tsuji, H. Nagashima and K. Sato, Tetra-
hedron Lett., 1982, 23, 3085; (c) D. N. Rubingh and P. M. Holland,
Cationic Surfactants: Physical Chemistry, CRC Press, Boca Raton,
FL, 1991chapter 7, p. 370.
1
a H NMR assay-based methodology19 using L-valine methyl
11 J. S. Yadav, B. V. S. Reddy, P. S. R. Reddy, A. K. Basak and
A. V. Narsaiah, Adv. Synth. Catal., 2004, 346, 77.
ester hydrochloride as a chiral derivatizing agent proved useful,
and 11b was shown to be formed in 19% ee.
12 (a) A. K. Sinha, R. Acharya and B. P. Joshi, J. Nat. Prod., 2002, 65,
764; (b) A. K. Sinha, B. P. Joshi and R. Dogra, US Pat., 6969778, 2003;
(c) B. P. Joshi, A. Sharma and A. K. Sinha, Tetrahedron, 2005, 61, 3075.
13 (a) B. V. D. O. Santos and M. C. D. O. Chaves, Biochem. Syst. Ecol.,
1999, 25, 539; (b) J. Hu and X. Feng, Planta Med., 2000, 66, 662.
14 A. K. Sinha, A. Sharma, R. Kumar and N. Sharma, Patent filed,
CSIR no. 0091NF, 2008.
Interestingly, the use of an increased amount of organo-
catalyst (19, 40 mol%) enhanced the ee of 11b up to 30% with
a 48% yield (see the ESI for detailsw). However, any further
increase in the amount of 19 did not increase the reaction yield
due to emulsion formation.
15 P. Coutrot, C. Grison and C. Bomont, J. Organomet. Chem., 1999,
586, 208.
16 (a) T. Hamori, S. Solyom, P. Berzsenyi, F. Andrasi and I. Tarnawa,
Bioorg. Med. Chem. Lett., 2000, 10, 899; (b) H. Kiuchi, K. Kogure
and M. Toyoda, Chem. Lett., 1984, 13, 341.
17 A. K. Sinha, B. P. Joshi, A. Sharma and V. Kumar, Aust. J. Chem.,
2007, 60, 124.
18 J. Seayad and B. List, Org. Biomol. Chem., 2005, 3, 719.
19 Y. Chi, T. J. Peelen and S. H. Gellman, Org. Lett., 2005, 7, 3469.
In conclusion, we have developed a new water-promoted
methodology for the direct synthesis of biologically and
synthetically important a-arylaldehydes bearing electron-
donating or halogen groups from arylalkenes using only
N-halosuccinimides and a phase transfer catalyst under
aqueous conditions. Importantly, the reaction doesn’t rely
on transition metal catalysts but instead proceeds through
ꢁc
This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 5299–5301 | 5301