4002
P. R. Blakemore et al. / Tetrahedron Letters 48 (2007) 3999–4002
B.; Rowlands, G. J.; Parmar, R. Chem. Commun. 2005,
4219–4221; Vinylmetals: (d) Sklute, G.; Marek, I. J. Am.
Chem. Soc. 2006, 128, 4642–4649, and references cited
therein; Metalated enol ethers: (e) Milne, J. E.; Kocienski,
P. J. Synthesis 2003, 584–592; Ferrocenylmetals: (f) Riant,
O.; Argouarch, G.; Guillaneux, D.; Samuel, O.; Kagan, H.
B. J. Org. Chem. 1998, 63, 3511–3514; (g) Albrow, V. E.;
Blake, A. J.; Fryatt, R.; Wilson, C.; Woodward, S. Eur. J.
Org. Chem. 2006, 2549–2557; (h) Kloetzing, R. J.; Kno-
chel, P. Tetrahedron: Asymmetry 2006, 17, 116–123;
Cyclopropylmetals: (i) Kopp, F.; Sklute, G.; Polburn,
K.; Marek, I.; Knochel, P. Org. Lett. 2005, 7, 3789–3791.
(1H, q, J = 6.7 Hz), 1.78 (1H, d, J = 6.7 Hz) ppm. Data
for anti-15 (X = Br): H NMR (300 MHz, CDCl3) d 7.68
1
(2H, d, J = 8.6 Hz), 7.48 (2H, d, J = 8.7 Hz), 4.57 (1H, q,
J = 6.8 Hz), 1.91 (3H, d, J = 6.8 Hz) ppm. Data for 16
(R = n-Bu): colorless oil; IR (neat) 2959, 1475, 1081, 1040,
1
1011, 825, 741 cmꢀ1; H NMR (300 MHz, CDCl3) d 7.53
(2H, d, J = 8.7 Hz), 7.46 (2H, d, J = 8.7 Hz), 2.74 (2H, t,
J = 7.2 Hz), 1.75–1.63 (1H, m), 1.60–1.50 (1H, m), 1.48–
1.32 (2H, m), 0.88 (3H, t, J = 7.2 Hz) ppm; 13C NMR
(75 MHz, CDCl3) d 142.7 (0), 137.3 (0), 129.7 (2C, 1),
125.6 (2C, 1), 57.3 (2), 24.2 (2), 22.1 (2), 13.8 (3) ppm.
Data for 16 (R = s-Bu, less polar isomer): colorless oil; IR
6. Satoh, T.; Takano, K. Tetrahedron 1996, 52, 2349–2358.
7. Hoffmann, R. W.; Nell, P. G.; Leo, R.; Harms, K. Chem.
Eur. J. 2000, 6, 3359–3365.
8. Blakemore, P. R.; Marsden, S. P.; Vater, H. D. Org. Lett.
2006, 8, 773–776.
9. Satoh and Takano reported the generation of complex
product mixtures from the reaction of an a-chloro-a-
protioalkyl tolyl sulfoxide and t-BuLi in THF (Ref. 6).
Durst et al. reported reactions of 1-chloroethyl phenyl
sulfoxide with n-BuLi, t-BuLi, and MeLi (in THF) and
obtained sulfoxide exchange products in yields of 22%,
9%, and 36%, respectively (Ref. 1g).
(neat) 2924, 1459, 1040, 827 cmꢀ1 1H NMR (400 MHz,
;
CDCl3) d 7.50–7.48 (4H, m), 2.51 (1H, sextet, J = 7.0 Hz),
1.94 (1H, d of quintet, J = 13.6, 7.2 Hz), 1.47 (1H, d of
quintet, J = 14.0, 7.0 Hz), 1.09 (3H, t, J = 7.2 Hz), 1.04
(3H, d, J = 6.8 Hz) ppm; 13C NMR (100 MHz, CDCl3) d
140.8 (0), 137.1 (0), 129.4 (2C, 1), 126.3 (2C, 1), 61.5 (1),
24.0 (2), 11.8 (3), 10.3 (3) ppm; HRMS (EI+) m/z
217.04536 (C10H1435ClOS requires 217.04539). Data for
16 (R = t-Bu): colorless oil; IR (neat) 2962, 1475, 1169,
1045, 1011, 825, 742 cmꢀ1; 1H NMR (300 MHz, CDCl3) d
7.53 (2H, d, J = 8.7 Hz), 7.46 (2H, d, J = 8.7 Hz), 1.16
(9 H, s) ppm; 13C NMR (75 MHz, CDCl3) d 138.8 (0),
137.6 (0), 128.7 (2C, 1), 127.6 (2C, 1), 56.1 (0), 22.7 (3C, 3)
ppm. Data for 16 (R = Me): colorless oil; IR (neat) 2970,
10. For a-halogenation of sulfoxides with N-halosuccini-
mides, see: (a) Jung, F.; Tin, K. C.; Durst, T. Int. J.
Sulfur Chem. 1973, 8, 1–4; (b) Drabowicz, J. Synthesis
1986, 831–833; (c) Satoh, T.; Oohara, T.; Ueda, Y.;
Yamakawa, K. Tetrahedron Lett. 1988, 29, 313–316.
11. Data for 14: colorless oil; IR (neat) 2978, 1475, 1391, 1051,
;
1476, 1090, 1052, 1011, 822, 741 cmꢀ1 1H NMR
(300 MHz, CDCl3) d 7.59 (2H, d, J = 8.7 Hz), 7.51 (2H,
d, J = 8.7 Hz), 2.71 (3H, s) ppm; 13C NMR (75 MHz,
CDCl3) d 144.5 (0), 137.4 (0), 129.8 (2C, 1), 125.1 (2C, 1),
44.3 (3) ppm. Data in agreement with those previously
reported, see: 16 (R = n-Bu) (a) Xia, M.; Chen, Z.-C.
Synth. Commun. 1997, 27, 1315–1320. 16 (R = t-Bu) (b)
Shelton, J. R.; Davis, K. E. Int. J. Sulfur Chem. 1973, 3,
197–204. 16 (R = Me) (c) Buchanan, G. W.; Reyes-
Zamora, C.; Clarke, D. E. Can. J. Chem. 1974, 52,
3895–3904.
825 cmꢀ1 1H NMR (300 MHz, CDCl3) d 7.51 (2H, d,
;
J = 8.1 Hz), 7.45 (2H, d, J = 8.1 Hz), 2.86 (1H, dq,
J = 13.2, 7.5 Hz), 2.70 (1H, dq, J = 13.2, 7.5 Hz), 1.15
(3H, t, J = 7.5 Hz) ppm; 13C NMR (75 MHz, CDCl3) d
141.8 (0), 137.0 (0), 129.4 (2C, 1), 125.6 (2C, 1), 50.2 (2),
5.8 (3) ppm. Data for 15 (X = Cl): colorless solid; mp 52–
54 °C (EtOAc/hexanes); IR (neat) 2980, 1475, 1082, 1058,
1
1012, 823, 742 cmꢀ1; H NMR (300 MHz, CDCl3) d 7.63
14. (a) Creger, P. L. J. Am. Chem. Soc. 1970, 92, 1396–1397;
(b) Seebach, D.; Boes, M.; Naef, R.; Schweizer, W. B. J.
Am. Chem. Soc. 1983, 105, 5390–5398; (c) Vedejs, E.; Lee,
N. J. Am. Chem. Soc. 1995, 117, 891–900.
(2H, d, J = 8.7 Hz), 7.52 (2H, d, J = 8.7 Hz), 4.71 (1H, q,
J = 6.6 Hz), 1.61 (3H, d, J = 6.6 Hz) ppm; 13C NMR
(75 MHz, CDCl3) d 138.4 (0), 137.0 (0), 129.2 (2C, 1),
127.3 (2C, 1), 70.3 (1), 17.0 (3) ppm. Data for 15 (X = Br):
oily solid; IR (neat) 2953, 1475, 1391, 1082, 1054, 822,
15. The possibility that anti-15 may arise from 15 via a base
catalyzed process or via a halide anion mediated substi-
tution (‘ping-pong’) mechanism was suggested by a
reviewer. Additional experiments have established that
neither pathway is a significant cause of epimerization for
15 (X = Cl). Thus, exposure of 15 (X = Cl) to excess LiCl
or LiBr in THF at temperatures ranging from ꢀ78 °C to
65 °C resulted in no observed reaction. Likewise, reaction
of 15 (X = Cl) with substoichiometric quantities (0.1–
0.25 equiv) of either LDA or t-BuLi did not in any
experiment result in the production of anti-15 in a quantity
greater than the amount of added base.
742 cmꢀ1 1H NMR (300 MHz, CDCl3) d 7.64 (2H, d,
;
J = 8.7 Hz), 7.51 (2H, d, J = 8.7 Hz), 4.74 (1H, q,
J = 6.6 Hz), 1.80 (3H, d, J = 6.6 Hz) ppm; 13C NMR
(75 MHz, CDCl3) d 138.6 (0), 137.7 (0), 129.3 (2C, 1),
127.5 (2C, 1), 61.7 (1), 18.0 (3) ppm. All data in agreement
with those previously reported, see: 14 (a) Shukla, V. G.;
Salgaonkar, P. D.; Akamanchi, K. G. J. Org. Chem. 2003,
68, 5422–5425. 15 (X = Cl and Br) (b) Cinquini, M.;
Colonna, S.; Landini, D.; Maia, A. M. J. Chem. Soc.,
Perkin Trans. 2 1976, 996–1000.
12. Solutions (0.20 M) of 15 in the indicated solvent were used
throughout. Alkylmetal reagents were dispensed as
the following standardized solutions: n-BuMgCl (2.4 M
in THF), n-BuLi (2.1 M in hexanes), s-BuLi (1.4 M in
cyclohexane), t-BuLi (1.5 M in pentane), MeLi (1.6 M in
Et2O).
16. Experiments in pentane and Et2O were also attempted but
gave irreproducible results owing to the poor solubility of
sulfoxide 15 (X = Cl) in these solvents at ꢀ78 °C.
17. Use of t-BuLi with PhMe solvent has now been verified as
optimal for the generation of enantioenriched Li-carbe-
noids for use in stereospecific reagent controlled homol-
ogation (StReCH) reactions, see: Blakemore, P. R.; Burge,
M. S. J. Am. Chem. Soc. 2007, 129, 3068–3069.
13. Data for anti-15 (X = Cl): 1H NMR (300 MHz, CDCl3) d
7.68 (2H, d, J = 8.7 Hz), 7.52 (2 H, d, J = 8.7 Hz), 4.48