a-methine proton to the vinyl group in the case of the major
anti isomer 26b, and to the 2,4-difluorophenyl group in the
case of syn isomers 24b and 25b. The stereochemistry of the
minor syn isomer 25b was unequivocally assigned by X-ray
crystallographic analysis (Fig. 1),18 and the structure of major
syn isomer 24b was inferred accordingly. The structures of the
major and minor anti isomers 26b and 27b followed from those
of the syn compounds, since the configuration of the quaternary
centre is set during the pericyclic process, and is unaffected by
the subsequent in situ decarboxylation step. The dCr reactions
of 23a–c are shown in Scheme 6, and the results collected in
Table 2.
Thus, rearrangement of 23a took place with an overall dia-
stereoisomeric ratio (dr) of 70 : 30, while that of 23b and 23c
showed dr’s of 77 : 23 and 85 : 15 respectively. The sense of
asymmetric induction evident in the major products is the
same as that observed previously in reactions of acyclic
substrates,15 taking into account the necessary boat-like
geometry of the reactive conformation (Scheme 7). It is
noteworthy that the dr is greatest for substrate 23c, which
has the sterically most demanding Ar group.
In summary, we have described the first transannular,
decarboxylative Claisen rearrangements, and have demonstrated
their use in the stereoselective formation of quaternary centres.
Extension of this methodology to larger rings, and use in total
synthesis will be reported in due course.
Inspection of the results in Table 2 reveals that the ratios of
syn to anti products ([24 + 25] : [26 + 27]) vary between 2 : 1
and 3 : 2. More importantly, the ratios [24 + 26] : [25 + 27]
are indicative of asymmetric induction from the sulfoximine
group, since these pairs of compounds arise through C–C
bond formation taking place with the same topicity.
We thank EPSRC (DTA-funded studentship to S.J.G., and
responsive-mode grant GR/T10268), Hoffmann–La Roche
(additional studentship support to S.J.G.) and Pfizer
(Industrial CASE studentship to S.E.L.) for support.
Notes and references
1 R. E. Ireland and R. H. Mueller, J. Am. Chem. Soc, 1972, 94, 5897;
For reviews of the Ireland–Claisen rearrangement, see:
(a) S. Pereira and M. Srebnik, Aldrichimica Acta, 1993, 26, 17;
(b) Y. Chai, S. Hong, H. A. Lindsay, C. McFarland and
M. McIntosh, Tetrahedron, 2002, 58, 2905.
2 For a review of the Claisen and related rearrangements, see:
A. M. Castro, Chem. Rev., 2004, 104, 2939.
3 For a review of catalysis of the Claisen rearrangement, see:
K. C. Majumdar, S. Alam and B. Chattopadhyay, Tetrahedron,
2008, 64, 597.
4 D. Bourgeois, D. Craig, N. P. King and D. M. Mountford, Angew.
Chem., Int. Ed., 2005, 44, 618.
5 D. Bourgeois, D. Craig, F. Grellepois, D. M. Mountford and A. J.
W. Stewart, Tetrahedron, 2006, 62, 483.
6 (a) D. Craig, N. P. King, J. T. Kley and D. M. Mountford,
Synthesis, 2005, 3279; (b) J. E. Camp and D. Craig, Tetrahedron
Lett., 2009, 50, 3503.
Scheme 6 dCr Reactions of 23a–c. Reagents and conditions: (i) BSA
(1.0 equiv.), KOAc (0.1. equiv.), DMF, microwave, 160 1C, 10 min.
7 D. Craig, F. Paina and S. C. Smith, Chem. Commun., 2008, 3408.
8 D. Craig and G. D. Henry, Eur. J. Org. Chem., 2006, 3558.
9 D. Craig and N. K. Slavov, Chem. Commun., 2008, 6054.
10 D. Craig and F. Grellepois, Org. Lett., 2005, 7, 463.
11 D. Craig, M. I. Lansdell and S. E. Lewis, Tetrahedron Lett., 2007,
48, 7861.
Table 2 dCr reactions of a-sulfoximinyl-g-aryl-e-lactones 23a–c
Ratio 24 : 25 :
26 : 27a
Yieldb
(%)
Substrate Ar
Products
12 M. M. Abelman, R. L. Funk and J. D. Munger, J. Am. Chem. Soc.,
1982, 104, 4030; R. L. Funk and J. D. Munger, J. Org. Chem.,
1985, 50, 707; M. M. Abelman, R. L. Funk and J. D. Munger,
Tetrahedron, 1986, 42, 2831; R. L. Funk, J. B. Stallman and
J. A. Wos, J. Am. Chem. Soc., 1993, 115, 8847.
13 A. G. Cameron and D. W. Knight, Tetrahedron Lett., 1985, 26,
3503.
14 R. E. Ireland, R. H. Mueller and A. K. Willard, J. Am. Chem. Soc.,
1976, 98, 2868.
23a
23b
23c
C6H5
24a : 25a :
26a : 27a
44 : 22 : 26 : 7 78
44 : 16 : 33 : 7 70
49 : 11 : 36 : 4 71
2,4-F2C6H3 24b : 25b :
26b : 27b
2,6-F2C6H3 24c : 25c :
26c : 27c
a
b
Determined by 1H NMR analysis of crude products. Isolated yield
of 24 + 25 + 26 + 27.
15 D. Craig, F. Grellepois and A. J. P. White, J. Org. Chem., 2005, 70,
6827.
16 Substrate 19 was synthesised as the RS enantiomer; substrate 20
was synthesised as the SS enantiomer.
17 Substrates 23a–c were synthesised as racemic mixtures.
18 Crystal data for 25b: C32H37F2NO3S2, M = 585.75, orthorhombic,
Pca21 (no. 29), a = 11.4277(3), b = 11.7915(3), c = 22.8410(5) A,
V = 3077.82(13) A3, Z = 4, Dc = 1.264 g cmÀ3, m(Mo-Ka) =
0.218 mmÀ1, T = 173 K, colourless platy needles, Oxford
Diffraction Xcalibur 3 diffractometer; 6964 independent measured
reflections (Rint = 0.0560), F2 refinement, R1(obs) = 0.0472,
wR2(all)
= 0.0918, 4734 independent observed absorption-
corrected reflections [|Fo| > 4s(|Fo|), 2ymax = 611], 366 parameters.
The absolute structure of 25b was determined by a combination of
R-factor tests [R1+ = 0.0472, R1À = 0.0479] and by use of the Flack
parameter [x+ = 0.00(6), xÀ = 1.00(6)]. CCDC 767566.
Scheme 7 Reactive conformations of 23.
ꢀc
This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 4991–4993 | 4993