3720 J . Org. Chem., Vol. 63, No. 11, 1998
Taber and Malcolm
While we have had some success,2e we are aware of
the limitations inherent in a transition-state model for
rhodium-mediated C-H insertion that attempts to pre-
dict product ratios on the basis of MM2 calculations.
Arbitrary decisions limiting the several degrees of free-
dom possible in the transition state could lead one to a
model for the “point of commitment” to cyclization that
would be far from reality. The work described here is
important because it offers experimental evidence for a
key rotational degree of freedom, the dihedral angle
between the ester carbonyl and the rhodium carbenoid.
between 3 M aqueous NaOH and CH2Cl2. The combined
organic extract was then dried (Na2SO4) and concentrated. The
residue was chromatographed to yield 1a (159 mg, 85% from
7a ) as a yellow oil. This product gave spectra consistent with
those previously reported for 1a .15
3-exo-(2-exo-(1-Na p h th yl))bor n yl 2-Dia zou n d eca n oa te
(1b). A dry 50 mL round-bottom flask was charged with a
94:6 mixture of 7b and 7a (1.49 g, 3.14 mmol), 25 mL of dry
CH2Cl2 (0.25M), and DBU (0.95 mL, 6.27 mmol). The tem-
perature was lowered to 0 °C, and p-nitrobenzenesulfonyl azide
(PNBSA) (1.43 g, 6.27 mmol) was added in the dark. The
reaction was stirred for 1 h, during which time the water bath
went from 0 °C to ambient temperature. The reaction mixture
was partitioned between 3 M aqueous NaOH and CH2Cl2. The
combined organic extract was then dried (Na2SO4) and con-
centrated. The residue was chromatographed to yield a 93:7
mixture of 1b and 1a (1.2 g, 84% yield for both compounds) as
a yellow oil. For 1b: TLC Rf (10% MTBE/petroleum ether) )
Exp er im en ta l P r oced u r es17
Com p u ta tion a l An a lysis. Structure minimization was
carried out using Mechanics as provided in the Tektronics
CAChe System Version 2.8. CAChe Mechanics uses an
augmented version of Allinger’s MM2 force field. Details of
this computational approach have been published.2e
1
0.50; IR (film) 2081, 1682, 784 cm-1; H NMR δ 8.1-7.3 (m,
7H), 5.52 (d, J ) 8.7 Hz, 1H), 4.07 (d, J ) 8.7 Hz, 1H), 2.0-
0.9 (m, 33H); 13C NMR δ u 175.3, 135.8, 133.5, 133.4, 49.3,
48.2, 42.6, 35.2, 34.8, 31.9, 31.8, 29.1, 28.8, 28.3, 27.5, 24.7,
24.4, 23.9, 22.6; d 149.6, 128.7, 127.0, 126.5, 125.9, 125.5,
125.0, 124.3, 123.6, 119.4, 79.9, 79.3, 55.5, 51.4, 51.2, 50.5, 43.5,
42.9, 24.1, 21.6, 14.9, 14.8, 14.1.
Meth yl 2-Acetylu n d eca n oa te (7a ). To a solution of
methyl acetoacetate (6) (4.5 mL, 42 mmol) in 20 mL of DME
were added potassium carbonate (5.8 g, 42 mmol) and tet-
rabutylammonium iodide (770 mg, 2.1 mmol). 1-Bromononane
(4.0 mL, 21 mmol) was introduced via syringe, and the mixture
was warmed to reflux for 24 h. The reaction mixture was then
cooled and partitioned between 3 M aqueous HCl and petro-
leum ether. The combined organic extracts were dried (Na2SO4)
and concentrated. The residue was distilled under reduced
pressure (bath ) 140 °C/0.5 mmHg), and the distillate was
chromatographed to give 7a as a colorless oil (3.50 g, 69% yield
from 1-bromononane). This product gave spectra consistent
with those previously reported for 7a .15
Rh od iu m -Med ia ted C-H In ser tion Rea ction s. The
CH2Cl2 was distilled over calcium hydride and then passed
through a pad of anhydrous K2CO3 just prior to use. The
requisite diazo compound (1a or 1b) was dried before use by
dilution of the sample with toluene and subsequent evapora-
tion. It was then diluted in the CH2Cl2 to a concentration of
approximately 0.25 M, and the temperature was adjusted. The
rhodium catalyst (1 mol %) was dissolved in 0.1 mL of CH2Cl2,
and the temperature of the catalyst solution was adjusted to
the experimental conditions desired. The catalyst solution was
then added to the substrate dropwise as rapidly as foaming
would allow and then stirred until the reaction was complete
as determined by TLC (usually within 1/2 h). The resulting
light green solution was filtered through silica and evaporated.
For the reaction at -78 °C, the solution was allowed to warm
to ambient temperature overnight.
3-exo-(2-exo-(1-Na p h th yl))bor n yl 2-Acetylu n d eca n oa te
(7b). A 100 mL sidearm flask was equipped with a Dean-
Stark water trap filled with 4 Å molecular sieve and a reflux
condenser. The flask was charged with methyl ester 7a (1.27
g, 5.23 mmol), naphthylborneol 5 (1.47 g, 5.23 mmol), DMAP
(13 mg, 0.105 mmol), and 50 mL of dry toluene. The solution
was warmed to reflux for 3 days and then cooled. It was then
partitioned between saturated aqueous ammonium chloride
and ethyl acetate. The combined organic extract was dried
(Na2SO4) and concentrated. The mixture was separated into
two fractions by column chromatography. One fraction con-
tained 0.04 mmol of 7a , 0.43 mmol of 7b, and 1.29 mmol of
recovered alcohol 5 and was not purified further. The second
fraction contained 1.21 mmol of unreacted 7a and 3.63 mmol
of 7b (quantitative yield based on starting materials recov-
ered). Most of the methyl ester was removed by distillation
(bath ) 140 °C/0.5 mmHg), yielding 1.62 g of a 94:6 mixture
In an unoptimized run, this procedure was applied to the
methyl diazo ester 1a . Reaction of 1a with Rh2Piv4 at ambient
temperature yielded a 3:1 mixture of cyclic esters (R,R)-3a and
(S,S)-3a to alkene 4a . Chromatography yielded the pure
racemic trans ester (40% from 1a ).
(R*,R*)-(2-P en tyl)cyclop en ta n em eth a n ol ((R,R)-8 a n d
(S,S)-8). A mixture of esters (3a ) 0.020 mmol, 4a ) 0.024
mmol, 3b ) 0.185 mmol, 4b ) 0.151 mmol) (total 159 mg, 0.380
mmol) was diluted in 2 mL of THF in a 5 mL reactivial. One
equivalent of LiAlH4 (14 mg, 0.38 mmol) was added to the
stirring solution, and the reaction was followed by TLC. Over
the next 4 h, the temperature was raised to 50 °C, and 2 more
equiv of LiAlH4 was added. When the reaction was judged
complete by TLC, it was cautiously quenched with 50 µL of
H2O, 50 µL of 3 M aqueous NaOH, and finally 150 µL of H2O.
The resultant slurry was filtered through Celite, and the salts
were rinsed with 20 mL of MTBE and 20 mL of acetone. The
filtrate was evaporated and chromatographed to yield 90.2 mg
(96%) of the recovered chiral alcohol 5 and a clean cut of a
mixture of alcohols (R,R)-8 and (S,S)-8 (20.1 mg, 57%). Yields
are based on a complete reaction where one would expect 0.336
mmol (94 mg) of 5 and 0.205 mmol (35 mg) of a mixture of
(R,R)-8 and (S,S)-8. For the clean (R,R)-8 and (S,S)-8: TLC
Rf (10% MTBE/petroleum ether) ) 0.18; IR (film) 3320, 1464,
of the expected chiral ester (7b) and methyl ester (7a ).
A
portion of the mixture was further distilled to give an analyti-
cal sample of 7b: TLC Rf (10% MTBE/petroleum ether) ) 0.55;
1
IR (film) 1738, 1716, 787 cm-1; H NMR δ 8.0-7.4 (m, 7H),
5.54 (dd, J ) 8.8, 4.9 Hz, 1H), 4.07 (d, J ) 7.9 Hz, 1H), 2.68 (t,
J ) 7.3 Hz, 0.5H), 2.54 (t, J ) 7.3 Hz, 0.5H), 2.2-0.6 (m, 36H);
13C NMR δ u 202.0, 168.8, 135.0, 133.5, 133.1, 49.3, 48.2, 42.4,
31.8, 29.3, 29.1, 29.0, 27.2, 27.0, 26.7, 23.7, 22.6; d 128.9, 127.2,
126.6, 126.1, 125.1, 124.5, 123.3, 80.4, 59.6, 55.2, 51.2, 27.6,
23.9, 21.4, 14.6, 14.0; EI MS m/z (rel intensity) 490 (M+, 9),
380 (8), 262 (30), 207 (13), 170 (100), 141 (34), 121 (10), 95 (8);
HRMS (calcd for C33H46O3) 490.3447, found 490.3428. Anal.
Calcd for C33H46O3: C, 80.77; H, 9.45. Found C, 80.68; H, 9.30.
Meth yl 2-Dia zou n d eca n oa te (1a ). A dry 5 mL reactivial
was charged with 7a (200 mg, 0.83 mmol), 2.5 mL of dry
CH2Cl2 (0.25M), and DBU (0.25 mL, 1.65 mmol). The tem-
perature was lowered to 0 °C, and p-nitrobenzenesulfonyl azide
(PNBSA) (377 mg, 1.65 mmol) was added in the dark. The
reaction was stirred for 1 h at 0 °C and 1 h at ambient
temperature. The reaction mixture was then partitioned
1070, 780 cm-1 1H NMR δ 3.61 (dd, J ) 10.4, 5.2 Hz, 1H),
;
3.42 (dd, J ) 10.4, 7.5 Hz, 1H), 1.8-1.1 (m, 15H), 0.85 (t, J )
6.7, 3H); 13C NMR δ u 66.8, 35.8, 32.7, 32.2, 29.4, 28.1, 24.4,
22.7; d 48.2, 42.1, 14.1; EI MS m/z (rel intensity) 152 (7), 131
(7), 109 (20), 96 (80), 81 (100), 67 (63), 55 (51). Anal. Calcd
for C11H20O: C, 77.58; H, 13.02. Found: C, 77.19; H, 12.64.
(R*,R*)-(2-P en tyl)cyclop en ta n em eth yl (R)-r-Meth oxy-
r-(tr iflu or om eth yl)p h en yla ceta te ((R,R,R)-9 a n d (S,S,R)-
9). The mixture of (R,R)-8 and (S,S)-8 (10 mg, 0.0587 mmol)
was diluted in 0.2 mL of pyridine that had been distilled from
(17) For general experimental procedures, see: Taber, D. F.;
Meagley, R. P.; Doren, D. J . J . Org. Chem. 1996, 61, 5723-5728.
Exceptions are noted.