J. Barluenga et al.
6.53 (s, 1H), 7.42 (brs, 1H), 7.49 ppm (s, 1H); 13C NMR (100 MHz,
CDCl3): d= 38.9 (CH2), 45.7 (CH2), 46.3 (CH2), 51.7 (CH3), 71.9 (C),
77.6 (CH), 78.8 (C), 110.2 (CH), 112.2 (CH2), 118.2 (CH2), 125.9 (C),
133.4 (CH), 140.7 (CH), 142.8 (CH), 143.3 ppm (C); LRMS (70 eV, EI):
m/z (%): 264 (8) [M]+, 214 (28), 173 (58), 145 (100), 125 (45), 117 (34),
95 (33); HRMS (70 eV, EI): calcd for C15H20O4: 264.1362; found:
264.1367 [M]+; elemental analysis calcd (%) for C15H20O4: C 68.16, H
7.63; found: C 68.27, H 7.74.
Acknowledgements
We gratefully acknowledge the Spanish MCYT (BQU2001–3853) and the
FICYT of Principado de Asturias (PR-01-GE-9) for financial support
and Merck Sharp & Dohme (UK) for generous support. I.P.-S. thanks
the Principado de Asturias (FICYT) for a predoctoral fellowship. M.G.S.
thanks the Ministerio de Educación, Ciencia y Deporte (Spain) for a
FPU predoctoral fellowship.
(1R*,2R*,3S*,4S*)-1-Allyl-3-(3,3-dimethyl-1-butynyl)-3-methoxy-2-
methyl-5-methylene-1,4-cyclohexanediol (8g): Pale yellow oil; Rf =0.15
1
(hexane/EtOAc 3:1); H NMR (300 MHz, CDCl3): d=1.23 (d, J=7.1 Hz,
3H), 1.29 (s, 9H), 1.72 (q, J=7.1 Hz, 1H), 2.24 (brs, 1H), 2.26 (brs, 1H),
2.30 (brs, 1H), 2.33–2.40 (m, 2H), 3.53 (s, 3H), 3.96 (s, 1H), 4.07 (brs,
1H), 5.05 (brs, 1H), 5.08 (brs, 1H), 5.13 (d, J=3.4 Hz, 1H), 5.27 (brs,
1H), 5.71–5.85 ppm (m, 1H); 13C NMR (100 MHz, CDCl3): d= 9.6
(CH3), 27.5 (C), 30.8 (3CH3), 44.0 (CH2), 45.0 (CH), 45.5 (CH2), 52.7
(CH3), 74.1 (C), 75.0 (C), 79.1 (CH), 83.1 (C), 98.7 (C), 110.8 (CH2),
116.2 (CH2), 133.5 (CH), 141.3 ppm (C); LRMS (70 eV, EI): m/z (%):
292 (0.4) [M]+, 260 (36) [MꢀCH3OH]+, 245 (41), 219 (31), 203 (58), 191
(59), 173 (37), 159 (48), 153 (66), 152 (75), 137 (47), 109 (94), 69 (100);
HRMS (70 eV, EI): calcd for C18H28O3: 292.2038 [M]+; found: 292.2047.
[1] Metal Carbenes in Organic Synthesis,Vol. 13: Topics Organomet.
Chem. (Ed.: K. H. Dötz), Springer-Verlag, Berlin, 2004.
[2] For reviews on multicomponent reactions see: a) G. H. Posner,
Chem. Rev. 1986, 86, 831; b) L. Weber, K. Illgen, M. Almstetter,
Synlett 1999, 366; c) A. Dömling, I. Ugi, Angew. Chem. 2000, 112,
3300; Angew. Chem. Int. Ed. 2000, 39, 3168; d) H. Bienaymé, C.
Hulme, G. Oddon, P. Schmitt, Chem. Eur. J. 2000, 6, 3321; e) A. J.
von Wangelin, H. Neumann, D. Gördes, S. Klaus, D. Strübing, M.
Beller, Chem. Eur. J. 2003, 9, 4286; f) J. Barluenga, M.A. Fernán-
dez-Rodríguez, E. Aguilar, J. Organomet. Chem. 2005, 690, 539.
[3] Preliminary communication: J. Barluenga, I. Pérez-Sánchez, E.
Rubio, J. Flórez, Angew. Chem. 2003, 115, 6040; Angew. Chem. Int.
Ed. 2003, 42, 5860.
(1R*,3S*,4S*)-3-Cyclopentyl-3-methoxy-1-methyl-5-methylene-1,4-cy-
clohexanediol (10b): Colorless solid; m.p. 128–1308C; Rf =0.20 (hexane/
1
EtOAc 3:1); H NMR (300 MHz, CDCl3): d= 1.20 (s, 3H), 1.40–1.67 (m,
8H), 1.75–1.81 (m, 1H), 1.93 (dd, J=14.7, 3.0 Hz, 1H), 2.15 (brd, J=
13.4 Hz, 1H), 2.25 (brd, J=6.5 Hz, 1H), 2.39 (dd, J=13.4, 3.1 Hz, 1H),
2.55 (quintet, J=8.6 Hz, 1H), 3.34 (s, 3H), 4.07 (brs, 1H), 4.22 (s, 1H),
5.02 (apparent s, 1H), 5.20 ppm (apparent s, 1H); 13C NMR (75 MHz,
CDCl3): d=25.3 (CH2), 25.8 (CH2), 27.0 (CH2), 28.7 (CH2), 29.2 (CH3),
38.6 (CH2), 42.1 (CH), 47.8 (CH2), 51.1 (CH3), 70.6 (C), 76.2 (CH), 83.0
(C), 109.9 (CH2), 145.2 ppm (C); LRMS (70 eV, EI): m/z (%): 241 (0.3)
[M+H]+, 240 (0.5) [M]+, 208 (28), 190 (46), 171 (29), 169 (42), 153 (44),
150 (30), 147 (23), 137 (55), 127 (38), 121 (31), 111 (42), 97 (37), 95 (49),
85 (31), 71 (100), 69 (40); HRMS (70 eV, EI): calcd for C14H24O3:
240.1725 [M]+; found: 240.1728; elemental analysis calcd (%) for
C14H24O3: C 69.96, H 10.07; found: C 69.70, H 10.18.
[4] J. Barluenga, J. Flórez, F. J. Fañanás, J. Organomet. Chem. 2001, 624,
5.
[5] C. P. Casey, W. R. Brunsvold, Inorg. Chem. 1977, 16, 391.
[6] J. M. Concellón, P. L. Bernad, Jr., Tetrahedron Lett. 1998, 39, 7967.
[7] a) J. Barluenga, J. Alonso, F. Rodríguez, F. J. Fañanás, Angew.
Chem. 2000, 112, 2555; Angew. Chem. Int. Ed. 2000, 39, 2459; b) J.
Barluenga, J. Alonso, F. J. Fañanás, J. Am. Chem. Soc. 2003, 125,
2610; c) J. Barluenga, J. Alonso, F. J. Fañanás, J. Borge, S. García-
Granda, Angew. Chem. 2004, 116, 5626; Angew. Chem. Int. Ed.
2004, 43, 5510; d) J. Barluenga, J. Alonso, F. J. Fañanás, Chem. Eur.
J. 2005, 11, 4995.
[8] a) H. Rudler, A. Parlier, B. Martín-Vaca, E. Garrier, J. Vaissermann,
Chem. Commun. 1999, 1439; b) H. Rudler, A. Parlier, T. Durand-
Réville, B. Martín-Vaca, M. Audouin, E. Garrier, V. Certal, J. Vais-
sermann, Tetrahedron 2000, 56, 5001; c) H. Rudler, A. Parlier, V.
Certal, G. Lastennet, M. Audouin, J. Vaissermann, Eur. J. Org.
Chem. 2004, 2471.
[9] a) K. Fuchibe, N. Iwasawa, Org. Lett. 2000, 2, 3297; b) K. Fuchibe,
N. Iwasawa, Chem. Eur. J. 2003, 9, 905.
[10] a) J. Barluenga, S. K. Nandy, Y. R. S. Laxmi, J. R. Suárez, I. Merino,
J. Flórez, S. García-Granda, J. Montejo-Bernardo, Chem. Eur. J.
2003, 9, 5725. See also: b) E. O. Fischer, U. Schubert, W. Kalbfus,
C. G. Kreiter, Z. Anorg. Allg. Chem. 1975, 416, 135.
[11] a) I. Lee, N. J. Cooper, J. Am. Chem. Soc. 1993, 115, 4389; b) H.
Stadtmüller, P. Knochel, Organometallics 1995, 14, 3163.
[12] K. H. Dötz, H. Fischer, P. Hofmann, F. R. Kreissl, U. Schubert, K.
Weiss, Transition Metal Carbene Complexes, Verlag Chemie, Wein-
heim, 1983.
(1R*,2R*,3S*,4S*)-1-Allyl-4-deuteriomethyl-3-methoxy-2-methyl-3-
phenylcyclopentanol (3 f): Butyllithium (1.1 mmol, 1.6m in hexanes,
0.69 mL) was added to a solution of (E)-1-methoxy-1-trimethylsilyloxy-
propene (1.1 mmol, 176 mg) in THF (2 mL) at ꢀ788C.[33] The mixture
was stirred for 15 min at -788C and then for 15 min at 08C. The resulting
solution of enolate 2a was then added at ꢀ788C to a solution of carbene
complex 1a (1 mmol, 312 mg) in THF (15 mL). After 15 min at ꢀ788C,
allylmagnesium bromide (2.5 mmol, 1m in Et2O, 2.5 mL) was added. The
resulting reaction mixture was stirred for 30 min at ꢀ788C and was then
warmed to room temperature and stirred for a further 20 min period.
After this time, the mixture was quenched with D2O (10 mL) and neu-
tralized with DCl (solution in D2O, ca. 12n, 1 mL). The reaction workup
was carried out as indicated above (general procedure). Column chroma-
tography on silica gel (hexane/EtOAc 9:1) afforded cyclopentanol 3 f as a
single diastereoisomer (0.84 mmol, 219 mg, 84%). Colorless oil; Rf =0.36
1
(hexane/EtOAc 9:1); H NMR (300 MHz, CDCl3): d=1.00 (d, J=7.1 Hz,
[13] a) C. P. Casey, T. J. Burkhardt, J. Am. Chem. Soc. 1973, 95, 5833;
b) C. P. Casey, W. R. Brunsvold, J. Organomet. Chem. 1974, 77, 345.
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Riedmüller, Chem. Ber. 1976, 109, 3358.
3H), 1.07 (brd, J=7.1 Hz, 2H), 1.69 (dd, J=13.9, 10.5 Hz, 1H), 1.91 (q,
J=7.1 Hz, 1H), 2.13–2.22 (m, 2H), 2.38–2.47 (m, 2H), 3.29 (s, 3H), 3.38
(brs, 1H), 5.09–5.15 (m, 2H), 5.83–5.97 (m, 1H), 7.29–7.42 ppm (m, 5H);
13C NMR (75 MHz, CDCl3): d= 7.3 (CH3), 14.1 (t, 1J
(C,D)=19.5 Hz,
A
[15] a) C. P. Casey, T. J. Burkhardt, C. A. Bunnell, J. C. Calabrese, J. Am.
Chem. Soc. 1977, 99, 2127; b) E. O. Fischer, W. Held, F. R. Kreissl,
A. Frank, G. Huttner, Chem. Ber. 1977, 110, 656; c) J. Barluenga, A.
Ballesteros, R. Bernardo de la Rúa, J. Santamaría, E. Rubio, M.
Tomás, J. Am. Chem. Soc. 2003, 125, 1834.
[16] a) C. P. Casey, T. J. Burkhardt, J. Am. Chem. Soc. 1972, 94, 6543;
b) C. P. Casey, S. H. Bertz, T. J. Burkhardt, Tetrahedron Lett. 1973,
14, 1421; c) E. O. Fischer, W. Held, J. Organomet. Chem. 1976, 112,
C59; d) J. Barluenga, P. L. Bernad, Jr., J. M. Concellón, Tetrahedron
Lett. 1994, 35, 9471; e) N. Iwasawa, M. Saitou, Chem. Lett. 1994,
231; f) J. Barluenga, A.A. Trabanco, J. Flórez, S. García-Granda, E.
Martín, J. Am. Chem. Soc. 1996, 118, 13099; g) B. Alcaide, L. Casar-
rubios, G. Domínguez, M.A. Sierra, Organometallics 1996, 15, 4612.
CH2D), 42.4 (CH), 43.2 (CH2), 46.0 (CH2), 52.0 (CH), 55.3 (CH3), 79.4
(C), 91.2 (C), 117.7 (CH2), 126.9 (CH), 127.0 (2CH), 128.1 (2CH), 134.6
(CH), 139.5 ppm (C); LRMS (70 eV, EI): m/z (%): 243 (13) [MꢀH2O]+,
229 (13), 214 (14), 188 (28), 149 (44), 146 (50), 137 (100), 117 (35), 105
(44); HRMS (70 eV, EI): calcd for C17H21DO [MꢀH2O]+: 243.1733;
found: 243.1730.
7234
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Chem. Eur. J. 2006, 12, 7225 – 7235