9 T. Manaka, S.-I. Nagayama, W. Desadee, N. Yajima,
T. Kumamoto, T. Watanabe, T. Ishikawa, M. Kawahata and
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67, 1399.
12 H. M. Kaiser, I. Zenz, W. F. Lo, A. Spannenberg, K. Schroder, H. Jiao,
¨
¨
D. Gordes, M. Beller and M. K. Tse, J. Org. Chem., 2007, 72, 8847.
13 M. Bera and S. Roy, Tetrahedron Lett., 2007, 48, 7144.
14 S. Mali and U. K. Nadir, Synlett, 2008, 108.
15 (a) E. Medina, A. Moyano, M. A. Pericas and A. Riera, J. Org.
Chem., 1998, 63, 8574 (organocopper reagents); (b) F. A. Davis,
C.-H. Liang and H. Liu, J. Org. Chem., 1997, 62, 3796 (organo-
magnesium reagents); (c) K. Bellos, H. Stamm and D. Speth, J. Org.
Chem., 1991, 56, 6846; (d) R. Falkenstein, T. Mall, D. Speth and
H. Speth, J. Org. Chem., 1993, 58, 7877 (organolithium reagents).
16 A. A. Cantrill, A. N. Jarvis, H. M. I. Osborn, A. Ouadi and
J. B. Sweeney, Synlett, 1996, 847.
17 H. Aoyama, N. Mimura, H. Ohno, K. Ishii, A. Toda,
H. Tamamura, A. Otaka, N. Fujii and T. Ibuka, Tetrahedron
Lett., 1997, 38, 7383.
18 For a demonstration of the effect of aziridine stereochemistry on
the regioselectivity of ring-opening by organocopper reagents, see:
P. Wipf and P. C. Fritch, J. Org. Chem., 1994, 59, 4875.
19 A. Otaka, F. Katagiri, T. Kinoshita, Y. Odagaki, S. Oishi,
H. Tamamura, N. Hamanaka and N. Fujii, J. Org. Chem., 2002,
67, 6152.
Fig. 2 The molecular structures of (ꢁ)-15 (left) and (ꢁ)-17 (right).
analysis. Structural assignment of 16 followed from the con-
version of one of the diastereoisomers into tetrahydropyran 17
on brief treatment with acid (Scheme 4). The X-ray structures
of 15 and 17 are shown in Fig. 2.25
It seems likely that the lithiated oxygen moiety in 9 and 12
interacts in an attractive sense with lithiated 4, directing ring-
opening to the proximal aziridine carbon.20 Supporting this
idea is the observation that reaction of the O-MOM analogue
of 12 with lithio-4b gave a mixture of regiosiomeric products,
corresponding to non-selective aziridine ring-opening.
In summary, we have shown that functionally diverse sulfur-
stabilised carbanionic species react stereospecifically with both
vinyl- and hydroxymethyl-containing 1,2,3-trisubstituted
aziridines with complete regioselectivity. We anticipate that
these transformations will be useful in the synthesis of alkaloids
and related structures, and we are currently investigating the
total synthesis of several natural product targets based on this
chemistry.
20 K. Fuji, T. Kawabata, Y. Kiryu and Y. Sugiura, Heterocycles,
1996, 42, 701.
21 Aziridine 10 has been synthesised in enantiomerically enriched
form: see ref. 20. In the present work the mono-TBDMS derivative
of Z-2-butene-1,4-diol22 was subjected to Sharpless aziridination
conditions (ref. 3) to provide (ꢁ)-10 in 72% yield.
22 P. V. Ramachandran, H. Liu, M. V. R. Reddy and H. C. Brown,
Org. Lett., 2003, 5, 3755.
23 For
145.
a review, see: T. Ibuka, Chem. Soc. Rev., 1998, 27,
24 We thank Mr Niels Tholen (Imperial College) for optimisation of
this reaction. This transformation also may be carried out using
1-methylindole (1.25 equiv. with respect to 11) in the presence of
ZnCl2 (0.35 equiv.) under microwave irradiation conditions
(CH2Cl2 [0.8 M], 80 1C, 2 ꢄ 30 min; 95%).
This research was supported by EPSRC (grant GR/S10445,
and CASE Studentship to C.J.T.H., with Knoll Pharmaceuticals
and GlaxoSmithKline), and the European Community Human
Capital and Mobility programme (contract number HPMF.CT-
1999-00262: Marie Curie Individual Fellowship to S.C.).
25 Crystal data for 5c: C34H35NO5S2, M = 601.75, orthorhombic, Pbca
(no. 61), a = 16.4954(2), b = 13.9284(3), c = 26.6078(5) A, V =
6113.26(19) A3, Z = 8, Dc = 1.308 g cmꢂ3, m(Mo-Ka) =
0.217 mmꢂ1, T = 173 K, colourless tablets, Oxford Diffraction
Notes and references
Xcalibur
3 diffractometer; 7155 independent measured reflec-
1 For reviews on aziridines, see: (a) W. H. Pearson, B. W. Lian and
S. C Bergmeier, in Comprehensive Heterocyclic Chemistry II, ed.
A. R. Katritzky, C. W. Rees and E. F. V. Scriven, Pergamon,
New York, NY, 1996, vol. 1A, pp. 1–60; (b) S. S. Murphree and
A. Padwa, Prog. Heterocycl. Chem., 2001, 13, 52; (c) W. McCoull
and F. A. Davis, Synthesis, 2000, 1347; (d) B. Zwanenburg and
P. T. Holte, Top. Curr. Chem., 2001, 216, 93; (e) J. B. Sweeney,
Chem. Soc. Rev., 2002, 31, 247; (f) X. E. Hu, Tetrahedron, 2004, 60,
2701; (g) Aziridines and Epoxides in Organic Synthesis, ed.
A. K. Yudin, Wiley-VCH, Weinheim, Germany, 2006.
tions (Rint = 0.050), F2 refinement, R1(obs) = 0.067, wR2(obs) =
0.141, 5780 independent observed absorption-corrected reflections
[|Fo| 4 4s(|Fo|), 2ymax = 571], 394 parameters. CCDC 698819. Crystal
data for 7: C29H33NO3S2, M = 507.68, orthorhombic, Pbca (no. 61),
a
= 15.6552(2), b = 12.3842(2), c = 28.0436(4) A, V =
5437.01(14) A3, Z = 8, Dc = 1.240 g cmꢂ3, m(Cu-Ka) =
2.009 mmꢂ1, T = 173 K, colourless tablets, Oxford Diffraction
Xcalibur PX Ultra diffractometer; 3002 independent measured reflec-
tions (Rint = 0.038), F2 refinement, R1(obs) = 0.042, wR2(obs) =
0.076, 1958 independent observed absorption-corrected reflections
[|Fo| 4 4s(|Fo|), 2ymax = 1041], 318 parameters. CCDC 698820.
Crystal data for 15: C34H35NO6S2, M = 617.75, orthorhombic, Pccn
(no. 56), a = 15.99842(7), b = 30.52231(13), c = 12.73593(6) A, V =
2 A. K. Ghosh, W. J. Thompson, M. K. Holloway, S. P. McKee,
T. T. Duong, H. Y. Lee, P. M. Munson, A. M. Smith, J. M. Wai,
P. L. Darke, J. A. Zugay, E. A. Emini, W. A. Schleif, J. R. Huff
and P. S. Anderson, J. Med. Chem., 1993, 36, 2300.
6219.07(5) A3, Z = 8, Dc = 1.320 g cmꢂ3, m(Cu-Ka) = 1.932 mmꢂ1
,
3 J. U. Jeong, B. Tao, I. Sagasser, H. Henniges and K. B. Sharpless,
J. Am. Chem. Soc., 1998, 120, 6844.
T = 173 K, colourless tablets, Oxford Diffraction Xcalibur PX Ultra
diffractometer; 6002 independent measured reflections (Rint = 0.050),
F2 refinement, R1(obs) = 0.038, wR2(obs) = 0.105, 4796 independent
4 We have found that a,b-aziridinoaldehydes decompose to give
complex mixtures on storage; this instability might account for the
low yields of 2 under Wittig and other methylenation conditions.
5 D. Craig, R. McCague, G. A. Potter and M. R. V. Williams,
Synlett, 1998, 58.
6 For reactions of lithiated 4d with 1,2-di-, 1,2,2-tri-, and symmetrical
1,2,3-trisubstituted aziridines, see: H.-J. Breternitz and
E. Schaumann, J. Chem. Soc., Perkin Trans. 1, 1999, 1927.
7 A. S. Dudnik, A. W. Sromek, M. Rubina, J. T. Kim, A. V. Kel’in
and V. Gevorgyan, J. Am. Chem. Soc., 2008, 130, 1440.
observed absorption-corrected reflections [|Fo| 4 4s(|Fo|), 2ymax
=
1421], 390 parameters. CCDC 698821. Crystal data for 17:
C31H36N2O6S2, M = 596.74, monoclinic, C2/c (no. 15), a =
15.217(9), b = 15.731(3), c = 26.981(5) A, b = 101.78(3)1,
V = 6323(4) A3, Z = 8, Dc = 1.254 g cmꢂ3, m(Mo-Ka) =
0.212 mmꢂ1, T = 213 K, colourless blocks, Bruker P4 diffractometer;
4093 independent measured reflections (Rint = 0.046), F2 refinement,
R1(obs) = 0.070, wR2(obs) = 0.141, 2042 independent observed
reflections [|Fo| 4 4s(|Fo|), 2ymax = 451], 383 parameters. CCDC
699430.
8 S. L. Crawley and R. L. Funk, Org. Lett., 2006, 8, 3995.
ꢃc
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