1936 J. Am. Chem. Soc., Vol. 118, No. 8, 1996
Paquette and Mitzel
important event.40,43 Clearly, additional studies of this entire
question would be welcomed.
(75 MHz, CDCl3) δ 97.2, 93.7, 87.4, 39.3, 28.9, 28.7, 26.3, 25.7. 25.6;
MS m/z (M+) calcd 172.1099, obsd 172.1093.
r-(Methoxymethoxy)cyclohexaneacetaldehyde (4). A magneti-
cally stirred solution of 9 (900 mg, 6.42 mmol) in a 1:1 mixture of
THF and DMF (30 mL) was treated with sodium hydride (277 mg,
11.56 mmol) and chloromethyl methyl ether (616 mg, 7.70 mmol),
and the reaction was allowed to proceed at 20 °C for 48 h. Water (25
mL) and CH2Cl2 (25 mL) were introduced, and the separated aqueous
layer was extracted with CH2Cl2 (2 × 30 mL). The combined organic
phases were dried and concentrated, and the residue was purified by
chromatography on silica gel (elution with 10:1 hexanes-ethyl acetate)
to give the protected alcohol as a colorless oil (945 mg, 80%): 1H
NMR (300 MHz, CDCl3) δ 5.70-5.58 (m, 1 H), 5.25-5.11 (m, 2 H),
4.69 (d, J ) 6.7 Hz, 1 H), 4.50 (d, J ) 6.7 Hz, 1 H), 3.70 (t, J ) 7.4
Hz, 1 H), 3.36 (s, 3 H), 1.94-1.00 (m, 11 H); 13C NMR (75 MHz,
CDCl3) δ 136.9, 118.0, 93.7, 82.5, 55.4, 42.2, 29.0, 26.6, 26.1, 26.0.
Despite the considerable success of the present investigation,
the precise mechanism of indium-promoted reactions remains
unclear. In the mid-1980s, the involvement of radical pairs was
advanced in explanation of tin-promoted allylations.44 Subse-
quent recourse to radical clock experiments demonstrated
unambiguously that radicals could not be involved.45 We have
come to favor a single electron transfer process similar to that
advanced by Chan.13b According to this reaction profile, the
allyl bromide approaches the surface of the indium metal where
the SET process generates the reactive radical anion/indium
radical cation pair E. These conditions operate, of course, only
A 630 mg (3.38 mmol) sample of this ether was ozonolyzed in the
predescribed manner and purified by flash chromatography on silica
gel to give 4 as an unstable colorless oil (472 mg, 75%): 1H NMR
(300 MHz, CDCl3) δ 9.62 (d, J ) 2.5 Hz, 1 H), 4.71 (d, J ) 6.8 Hz,
1 H), 4.66 (d, J ) 6.8 Hz, 1 H), 3.65 (dd, J ) 5.5, 3.1 Hz, 1 H), 3.39
(s, 3 H), 1.81-1.64 (m, 6 H), 1.28-1.17 (m, 5 H); 13C NMR (75 MHz,
CDCl3) δ 203.6, 97.0, 86.5, 55.9, 39.5, 28.9, 27.8, 26.1, 26.0, 25.9.
Prototypical Allylation Reactions. A. In H2O. A magnetically
stirred solution of 4 (150 mg, 0.806 mmol) in water (8.9 mL) was
treated with indium powder (101 mg, 0.887 mmol) and allyl bromide
(145 mg, 1.21 mmol). The reaction was allowed to proceed until no
4 remained (TLC analysis). Ethyl acetate was added, stirring was
maintained for 60 min, and the separated aqueous phase was extracted
with ethyl acetate (2 × 20 mL). The combined organic layers were
dried and evaporated. The residue was taken up in anhydrous methanol
(15 mL) containing a few milligrams of p-toluenesulfonic acid and
refluxed for 12 h to provide the diol. The methanol was removed in
vacuo and replaced by acetone (15 mL). The resulting solution was
stirred for 6 h and concentrated to leave an oil, purification of which
was accomplished by flash chromatography on silica gel (elution with
50:1 hexanes-ethyl acetate) to give the acetonide in 80-95% yield
(Table 1).
The determination of diastereomer composition was performed as
described by Keck.25 The key identifying NMR signals are as
follows: syn, dd at δ 3.46 and 13C absorptions at 107.9, 84.5, and 78.0
ppm. For the anti isomer: dd at δ 3.73 and 13C peaks at 107.2, 82.3,
and 76.9 ppm.
Comparable processing of 7 (200 mg, 1.54 mmol) afforded 207 mg
(83%) of a 1:3.2 mixture of syn and anti alcohols.50 Syn isomer: 1H
NMR (250 MHz, CDCl3) δ 5.93-5.76 (m, 1 H), 5.12 (d, J ) 17 Hz,
1 H), 5.11 (d, J ) 10.5 Hz, 1 H), 4.07-3.95 (m, 2 H), 3.78-3.67 (m,
1 H), 3.58 (quintet, J ) 6.3 Hz, 1 H), 3.27-2.19 (series of m, 3 H),
1.43 (s, 3 H), 1.36 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ 134.2, 117.8,
109.4, 78.5, 71.5, 66.0, 38.2, 27.0, 25.3. Anti isomer: 1H NMR (250
MHz, CDCl3) δ 5.92-5.75 (m, 1 H), 5.25 (d, J ) 16 Hz, 1 H), 5.13
(d, J ) 10.5 Hz, 1 H), 4.05-3.87 (m, 3 H) 3.77 (dq, J ) 8.8, 4.4 Hz,
1 H), 2.43-2.10 (m, 2 H), 2.00 (d, J ) 3.4 Hz, 1 H), 1.43 (s, 3 H),
1.37 (s, 3); 13C NMR (75 MHz, CDCl3) δ 133.9, 118.2, 109.0, 78.1,
70.4, 65.2, 37.6, 26.5, 25.2.
when indium metal is present as a reactant. Acyclic diastereo-
facial control is presently recognized to occur in a wide range
of reactions.46,47 Suffice it to indicate at this point that the
preformation of allylindium reagents may well bypass the
involvement of E, suggesting an alternative pathway involving
the more conventional species F can also operate.17a,48 Proper
selection of reaction conditions could alter the precise pathway
at work.
Experimental Section49
5-Cyclohexyl-1,3-dioxolan-4-ol (3). A solution of vinylmagnesium
bromide in THF [from 11.36 g (107.2 mmol) of vinyl bromide] was
treated dropwise with cyclohexanecarboxaldehyde (3.00 g, 26.8 mmol).
The reaction mixture was refluxed for 5 h, cooled to 20 °C, treated
with 1 N HCl, and extracted with ether (4 × 50 mL). The combined
organic layers were washed sequentially with 1 N HCl, water, and brine,
then dried and evaporated. The residue was purified by chromatography
on silica gel (elution with 4:1 hexanes-ethyl acetate) to give 9 as a
colorless oil (3.60 g, 94%): 1H NMR (300 MHz, CDCl3) δ 5.85 (m,
1 H), 5.13 (m, 1 H), 3.83 (t, J ) 6.4 Hz, 1 H), 1.86-0.95 (series of m,
11 H); 13C NMR (75 MHz, CDCl3) δ 139.8, 115.4, 76.6, 43.5, 29.0,
28.3, 26.5, 26.1, 26.0.
A solution of 9 (1.00 g, 7.14 mmol) in CH2Cl2 (65 mL) was cooled
to -78 °C, ozonolyzed for 15 min, purged with oxygen, and treated
with dimethyl sulfide (12 mL). After 30 min, the cooling bath was
removed and the reaction mixture was stirred at 20 °C for 15 h prior
to solvent evaporation. Flash chromatographic purification (silica gel,
elution with 5:1 hexanes-ethyl acetate) gave 3 as a colorless oily
diasteromeric mixture (858 mg, 70%): 1H NMR (300 MHz, CDCl3) δ
5.25 (d, J ) 2.9 Hz, 1 H), 5.08 (d, J ) 9.8 Hz, 2 H), 3.50 (d, J ) 2.9
Hz, 1 H), 3.34 (br s, 1 H), 1.83-1.01 (series of m, 11 H); 13C NMR
Analogous treatment of 8 (100 mg, 0.463 mmol) gave rise to 94 mg
(78%) of a 1:2 mixture of syn and anti alcohols.24 Syn isomer: 1H
NMR (300 MHz, CDCl3) δ 5.82 (m, 1 H), 5.15 (m, 2 H), 3.78 (m, 2
H), 3.59 (m, 1 H), 3.19 (m, 1 H), 2.98 (dd, J ) 4.4, 7.5 Hz, 1 H), 2.37
(t, J ) 6.7 Hz, 2 H), 2.21 (br s, 1 H), 0.91 (s, 9 H), 0.10 (s, 3 H), 0.09
(s, 3 H); 13C NMR (75 MHz, CDCl3) δ 133.2, 118.3, 68.9, 61.6, 59.8,
57.6, 38.7, 25.8 (3 C), 18.2, -5.3, -5.4. Anti isomer: 1H NMR (300
MHz, CDCl3) δ 5.89 (m, 1 H), 5.25 (m, 2 H), 4.01 (dd, J ) 5.6, 11.6
Hz, 1 H), 3.71 (dd, J ) 6.5, 11.6 Hz, 1 H), 3.57 (m, 1 H), 3.14 (m, 1
H), 2.94 (dd, J ) 4.3, 7.9 Hz, 1 H), 2.69 (d, J ) 1.7 Hz, 1 H), 2.42 (m,
2 H), 0.89 (s, 9 H), 0.09 (s, 3 H), 0.08 (s, 3 H); 13C NMR (75 MHz,
CDCl3) δ 133.5, 118.1, 69.2, 62.0, 58.3, 55.4, 39.4, 25.8 (3 C), 18.2,
-5.3, -5.5.
(43) (a) Poll, T.; Metter, J. O.; Helmchen, G. Angew. Chem., Int. Ed.
Engl. 1985, 24, 112. (b) Buhro, W. E.; Georgiou, S.; Ferna´ndez, J. M.;
Patton, A. T.; Strouse, C. E.; Gladysz, J. A. Organometallics 1986, 5, 956.
(c) Arai, M.; Kawasuji, T.; Nakamura, E. J. Org. Chem. 1993, 58, 5121.
(44) (a) Petrier, C.; Luche, J. L. J. Org. Chem. 1985, 50, 910. (b) Einhorn,
C.; Luche, J. L. J. Organomet. Chem. 1987, 322, 177.
(45) Wilson, S. R.; Guazzaroni, M. E. J. Org. Chem. 1989, 54, 3087.
(46) Porter, N. A.; Giese, B.; Curran, D. P. Acc. Chem. Res. 1991, 24,
296.
(47) Smadja, W. Synlett 1994, 1.
(48) Marshall, J. A.; Hinkle, K. W. J. Org. Chem. 1995, 60, 1920.
(49) For generic experimental details, see: Paquette, L. A.; Lobben, P.
C. J. Am. Chem. Soc. 1996, 118, 1917.
(50) (a) Hoffmann, R. W.; Endesfelder, A.; Zeiss, H.-J. Carbohydrate
Res. 1983, 23, 320. (b) Roush, W. R.; Walts, A. E.; Hoong, L. K. J. Am.
Chem. Soc. 1985, 107, 8186.