7142 J . Org. Chem., Vol. 65, No. 21, 2000
Baldwin and Burrell
H), 1.45-1.61 (m, 1 H), 1.12 (d, J ) 6.59 Hz, 3 H) (compare
ref 3 and 16); 13C NMR δ 175.4, 51.5, 45.6, 35.1, 26.4, 21.3,
21.2; MS m/z (rel intensity) 128 (3, M+), 113 (15), 97 (19), 87
(100), 69 (64), 55 (55), 41 (54).
resolved. The maze of reported structural interconver-
sions relating (+)-1 with other molecules is complicated
and convoluted; the mere definition of absolute stereo-
chemistry for (1R,2S)-(+)-1 does not by itself lead to fully
satisfactory and consistent reinterpretations of all ac-
counts in the literature, but some readings of the data
do seem more plausible than others.14 In particular, we
believe the (+) isomer of cis-3-oxabicyclo-[3.2.0]heptan-
2-one is indeed (1S,5R)-14.15
For the immediate purposes of this work, the essential
stereochemical point is that a great hazard has been
avoided. To have relied on the assignment of absolute
stereochemistry (1S,2R) for (+)-1 provided by the litera-
ture7 would have led to reversed configurational asssign-
ments for the four 1-(E)-propenyl-2-methylcyclobutanes
and hence to erroneous inferences on the stereochemistry
of the thermal reactions converting them into mixtures
of seven dimethylcyclohexenes.
With absolute stereochemistry assignments now se-
cure, for both a key synthetic intermediate, (1R,2S)-(+)-
1, which may be converted readily into (1R,2S)-10 and
(1S,2S)-11, and for the six chiral 3,4- and 3,6-dimethyl-
cyclohexenes,13 the stage is set for synthetic, kinetic, and
analytical work which should unveil the stereochemical
complexities and preferences characteristic of the thermal
vinylcyclobutane-to-cyclohexene isomerizations of the
four 1-(E)-propenyl-2-methylcyclobutanes.
cis-2-Meth ylcyclobu ta n em eth a n ol ((()-6) and tr a n s-2-
m eth ylcyclobu ta n em eth a n ol ((()-7). A 40:60 mixture (1.5
g, 13.2 mmol) of acids (()-4 and (()-5 in ether (10 mL) was
added dropwise to a suspension of LiAlH4 (0.5 g, 13.2 mmol)
in ether (60 mL) at 0 °C.16 The mixture was warmed to room
temperature and stirred for 24 h under argon. At that time,
the flask was fitted with a reflux condenser and the solution
was refluxed for 1.5 h. The solution was cooled to 0 °C and
carefully quenched with water (10 mL). The organic layer was
removed and the aqueous layer was acidified with 2 N HCl
(50 mL). The aqueous layer was then extracted with ether (4
× 40 mL). The combined organic material was dried (MgSO4),
filtered, and concentrated by distillation. The residue was
purified by column chromatography (silica gel, hexanes:ethyl
acetate, 1:9) to give 1.1 g (84%) of cis-2-methylcyclobutane-
methanol ((()-6) and trans-2-methylcyclobutane-methanol
((()-7) as a 40:60 mixture according to analytical GC. Separa-
tion of the isomers in pure form was done with preparative
GC (1-m, 17% Carbowax, 100 °C). For (()-6:1H NMR δ 3.86-
3.72 (m, 1 H), 3.56-3.69 (m, 1 H), 2.42-2.63 (m, 2 H), 1.91-
2.17 (m, 2 H), 1.46-1.73 (m, 2 H), 1.11 (br s, 1 H), 1.04 (d, J
) 6.86 Hz, 3 H) (compare ref 16); 13C NMR δ 63.6, 39.3, 30.9,
26.5, 21.3, 15.6; MS m/z (rel intensity) 82 (11), 72 (9), 67 (42),
57 (100), 41 (55), 39 (42). For (()-7: 1H NMR δ 3.60 (br s, 2
H), 1.87-2.18 (m, 4 H), 1.39-1.65 (m, 2 H), 1.47 (br s, 1 H),
1.07 (d, J ) 6.31 Hz, 3 H) (compare ref 16); 13C NMR δ 66.7,
45.4, 33.4, 26.4, 21.2, 21.0; MS m/z (rel intensity) 82 (13), 72
(12), 67 (47), 57 (100), 41 (58), 39 (42).
Exp er im en ta l Section
cis-2-Meth ylcyclobu ta n eca r boxa ld eh yd e ((()-8) a n d
tr a n s-2-Meth ylcyclobu ta n eca r boxa ld eh yd e ((()-9).17 To
a 100-mL flask were added PCC18 (2.0 g, 9.2 mmol) and dry
CH2Cl2 (40 mL). A 40:60 mixture (0.6 g, 6.1 mmol) of (()-6
and (()-7 in CH2Cl2 (10 mL) was added dropwise to the PCC
solution over 5 h. The reaction mixture was stirred for an
additional 2 h at room temperature and then diluted with 40
mL of ether. The brown suspension was filtered through
Florisil. The black tar that remained in the flask was washed
with ether (3 × 30 mL), the washings were filtered through
Florisil, and the Florisil was washed with ether (60 mL). The
combined ethereal material was concentrated by distillation
to give (()-8 and (()-9 (0.54 g, 93%, cis/trans 40:60) as a 30%
solution in ether according to analytical GC. The aldehydes
were separated and purified through preparative GC (1-m,
17% Carbowax, 78 °C). (()-8: 1H NMR δ 9.87 (d, J ) 2.47 Hz,
1 H), 3.14-3.27 (m, 1 H), 2.81-2.99 (m, 1 H), 2.35-2.50 (m, 1
H), 2.14-2.28 (m, 1 H), 1.91-2.05 (m, 1 H), 1.58-1.70 (m, 1
H), 1.13 (d, J ) 7.13 Hz, 3 H); 13C NMR δ 204.7, 48.8, 33.6,
27.0, 18.0, 17.2; MS m/z (rel intensity) 98 (2, M+), 83 (23), 69
(58), 57 (92), 55 (44), 42 (71), 41 (100), 39 (69). (()-9: 1H NMR
δ 9.70 (d, J ) 2.47 Hz, 1 H), 2.54-2.82 (m, 2 H), 1.94-2.20
(m, 3 H), 1.55-1.73 (m, 1 H), 1.16 (d, J ) 6.59 Hz, 3 H); 13C
NMR δ 196.4, 47.2, 25.8, 20.2, 14.9, 12.1; MS m/z (rel intensity)
98 (4, M+), 83 (20), 69 (66), 57 (64), 55 (36), 42 (62), 41 (100),
39 (60).
cis-2-Met h ylcyclob u t a n eca r b oxylic a cid ((()-4) and
tr a n s-2-m eth ylcyclobu ta n eca r boxylic a cid ((()-5) were
prepared from 1,3-dibromobutane and diethyl malonate.6
A
sample of the intermediate diester 3 (bp 95-115 °C (15 mm),
lit.6b bp 70-72.5 °C (1.0 mm)) was purified by preparative GC
(1-m, 10% SE-30, 110 °C): 1H NMR δ 4.08-4.30 (m, 4 H),
3.05-3.20 (m, 1 H), 2.58-2.72 (m, 1 H), 1.98-2.18 (m, 2 H),
1.60-1.76 (m, 1 H), 1.20-1.32 (m, 6 H), 1.05 (d, J ) 7.14 Hz,
3 H); MS m/z (rel intensity) 214 (1, M+), 185 (4), 173 (32), 169
(30), 160 (14), 140 (12), 127 (100), 122 (46), 113 (16), 99 (48),
67 (22), 55 (17), 41 (25), 29 (81).
Hydrolysis and decarboxylation of 3 led to distilled (()-4
and (()-5, collected as a clear oil. Analytical GC showed this
material to be a 40:60 mixture of cis acid (()-4 and trans acid
(()-5. Both were isolated in pure form through preparative
GC (1-m, 17% Carbowax, 165 °C). (()-4: 1H NMR δ 3.19-
3.31 (m, 1 H), 2.22-2.90 (m, 1 H), 2.27-2.41 (m, 1 H), 1.94-
2.22 (m, 2 H), 1.58-1.72 (m, 1 H), 1.12 (d, J ) 7.13 Hz, 3 H)
(compare ref 7); 13C NMR δ 180.3, 41.7, 32.8, 26.2, 19.9, 16.9;
MS m/z (rel intensity) 114 (1, M+), 99 (8), 86 (11), 73 (100), 68
(26), 55 (30), 42 (45), 41 (40), 39 (32). (()-5: 1H NMR δ 2.53-
2.75 (m, 2 H), 1.96-2.21 (m, 3 H), 1.48-1.63 (m, 1 H), 1.14 (d,
J ) 6.59 Hz, 3 H); 13C NMR δ 180.2, 45.4, 35.3, 26.4, 21.1,
21.1; MS m/z (rel intensity) 114 (2, M+), 99 (8), 85 (60), 73
(100), 68 (32), 55 (43), 42 (72), 41 (65), 39 (57).
cis-1-Meth oxycar bon yl-2-m eth ylcyclobu tan e ((()-1) and
tr a n s-1-m et h oxyca r b on yl-2-m et h ylcyclob u t a n e ((()-2)
were prepared from the mixture of acids (()-4 and (()-5
through a conventional esterification with diazomethane in
ether. A 40:60 mixture of cis/trans isomers was obtained
according to analytical GC. They were separated and purified
by preparative GC (1-m, 17% Carbowax, 85 °C). (()-1: 1H NMR
δ 3.69 (s, 3 H), 3.15-3.27 (m, 1 H), 2.67-2.84 (m, 1 H), 2.29-
2.43 (m, 1 H), 1.93-2.20 (m, 2 H), 1.55-1.70 (m, 1 H), 1.03 (d,
J ) 7.13 Hz, 3 H) (compare ref 3, 7, and 16); 13C NMR δ 174.6,
51.2, 41.7, 32.8, 26.3, 20.2, 17.0; MS m/z (rel intensity) 128 (2,
M+), 113 (10), 97 (12), 87 (100), 69 (43), 55 (73), 41 (55). (()-2:
1H NMR δ 3.67 (s, 3 H), 2.48-2.71 (m, 2 H), 1.94-2.18 (m, 3
1,1-Diiod oeth a n e was prepared following a literature
procedure.19 The two-step sequence afforded distilled material
of bp 60-61 °C (12 mm) (lit.19 bp 60-61 °C (12 mm)): 1H NMR
δ 5.22 (qd, J ) 6.58, 1.10 Hz, 1 H), 2.92 (dd, J ) 6.58, 1.10
Hz, 3 H) (compare ref 20); 13C NMR δ 38.9, -39.3; MS m/z
(rel intensity) 282 (40, M+), 254 (16), 155 (100), 127 (51).
(16) Hill, E. A.; Chen, A. T.; Doughty, A. J . Am. Chem. Soc. 1976,
98, 167-170.
(17) Kazanskii, B. A.; Lukina, M. Yu. Dokl. Akad. Nauk SSSR 1954,
94, 887-889; Chem. Abstr. 1955, 49, 3030i.
(18) Corey, E. J .; Suggs, J . W. Tetrahedron Lett. 1975, 2647-2650.
(19) Friedrich, E. C.; Falling, S. N.; Lyons, D. E. Synth. Commun.
1975, 5, 33-36.
(15) J akovac, I. J .; Goodbrand, H. B.; Lok, K. P.; J ones, J . B. J . Am.
Chem. Soc. 1982, 104, 4659-4665.
(20) Neuman, R. C.; Rahm, M. L. J . Org. Chem. 1966, 31, 1857-
1859.