Simple preparation of α-diazo esters

Article abstract of DOI:10.1021/jo048011o

(Chemical Equation Presented) The TiCl₄-mediated reaction of an ester with benzoyl chloride results in high yields of the α-benzoylated ester. Diazo transfer of the benzoylated ester utilizing p- acetoamidobenzenesulfonyl azide affords the α-diazo ester in good yield. Using this simplified procedure, it is easy to prepare gram quantities of α-diazo esters.

Full text of DOI:10.1021/jo048011o

chloride, triethylamine, and acetonitrile at room tem-
perature converts an ester to the R-benzoylated ester
(method A). While this procedure worked well with
methyl esters (Table 1), yields were lower with branched
esters. We found that the addition of triethylamine before
the addition of the titanium(IV) chloride provided a buffer
against hydrolysis, thereby resulting in higher yields of
the R-benzoylated ester (method B). Utilizing either
method, we could then effect diazo transfer directly on
the crude benzoylated ester. The diazo ester so prepared
is usually pure enough to carry directly into subsequent
transformations.
Simple Preparation of r-Diazo Esters
Douglass F. Taber,* Ritesh B. Sheth, and
Pramod V. Joshi
Department of Chemistry & Biochemistry,
University of Delaware, Newark, Delaware 19716
taberdf@udel.edu
Received November 9, 2004
The TiCl4-mediated reaction of an ester with benzoyl chlo-
ride results in high yields of the R-benzoylated ester. Diazo
transfer of the benzoylated ester utilizing p-acetoamidoben-
zenesulfonyl azide affords the R-diazo ester in good yield.
Using this simplified procedure, it is easy to prepare gram
quantities of R-diazo esters.
R-Diazo esters are versatile intermediates in organic
synthesis.10-12 Rhodium(II) octanoate (5 mol %, CH2Cl2,
rt) efficiently catalyzes the hetero-H insertion of R-diazo
esters (Scheme 1). â-Hydride elimination to form the (Z)
alkene 713 is always a competing side reaction. Neverthe-
less, N-H, O-H, and S-H insertions proceed smoothly.
We expect that the diazo transfer procedure described
here will make R-diazo esters readily available as inter-
mediates for organic synthesis.
Several years ago, we reported a new method for the
diastereoselective construction of cyclopentanes, diazo
transfer followed by rhodium-mediated C-H insertion,
e.g., 2a to 3a.1 The key to this approach was the diazo
transfer to the ester.
Experimental Section
Representative Benzoylation Procedure by Method A.
Titanium tetrachloride (2.87 g, 15 mmol) was added over 30 min
to a solution of benzoyl chloride (4.26 g, 30 mmol) and methyl
tetradecanoate 1a (2.45 g, 10 mmol) in 10 mL of dry CH3CN at
0 °C. After 15 min, triethylamine (6.13 g, 60 mmol) was added
over 30 min. The mixture was warmed to reflux for 15 min. The
mixture was cooled, then partitioned between water and EtOAc
(5) Taber, D. F.; Herr, R. J.; Pack, S. K. J. Org. Chem. 1996, 61,
2908.
We found2 that benzoylation followed by diazo transfer
was a general method for the preparation of R-diazo
esters. The original procedure was to condense the
methyl ester with sodium hydride and methyl benzoate.
The yield of this reaction was limited by the continued
reaction of the sodium methoxide with the benzoylated
ester. Danheiser introduced 2,2,2-trifluoroethyl trifluo-
roacetate and lithium bis(trimethylsilyl) amide as a more
efficient acylation method.3 While effective, this method
requires the use of an expensive strong base and cryo-
genic conditions.
(6) Sundar, N.; Bhat, V. Synth. Commun. 1998, 28, 2311.
(7) Aitken, R. A.; Armstrong, J. M.; Drysdale, M. J.; Ross, F. C.;
Ryan, B. M. J. Chem. Soc., Perkin Trans. 1 1999, 5, 593.
(8) Queignec, R.; Kirschleger, B.; Lambert, F.; Aboutaj, M. Synth.
Commun. 1988, 18, 1213.
(9) Calo, V.; Nacci, A.; Lopez, L.; Napola, A. Tetrahedron Lett 2001,
42, 4701.
(10) For examples of Rh-mediated O-H insertion, see: (a) Doyle,
M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for Organic
Synthesis with Diazo Compounds. From Cyclopropanes to Ylides;
Wiley-Interscience: New York, 1998. (b) Miller, D. J.; Moody, D. J.
Tetrahedron 1995, 40, 10811. (c) Aller, E.; Brown, D. S.; Cox, G. G.;
Miller, D. J.; Moody, C. J. J. Org. Chem. 1995, 60, 4449. (d) Sengupta,
S.; Das, D.; Sarma, D. S. Tetrahedron Lett. 1996, 37, 8815 (e) Moody,
C. J.; Miller, D. J. Tetrahedron 1998, 54, 2257.
Building on the results of Tanabe,4 we have now found
that the combination of benzoyl chloride, titanium(IV)
(11) For examples of Rh-mediated S-H insertion, see: McKervey,
M. A. Tetrahedron Let. 1982, 23, 2509.
(12) For examples of Rh-mediated N-H insertion, see: (a) Aller,
E.; Buck, R. T.; Drysdale, M. J.; Ferris, L.; Haigh, D.; Moody, C. J.;
Pearson, N. D.; Sanghera, J. B. J. Chem. Soc., Perkins Trans. 1996,
24, 2879. (b) Davis, F. A.; Fang, T.; Goswami, R. Org Lett. 2002, 4,
1599. (c) Buck, R. T.; Clarke, P. A.; Coe, Diane M., Drysdale, M. J.;
Ferris, L.; Haigh, D.; Moody, C. J.; Pearson, N. D.; Swann, E. Chem.
Eur. J. 2000, 6, 2160. (d) Ferris, L.; Haigh, D.; Moody, C. J. J. Chem.
Soc., Perkin Trans. 1996, 24, 2885.
(1) Taber, D. F.; Hennessey, M. J.; Louey, J. P. J. Org. Chem. 1992,
57, 436.
(2) Taber, D. F.; You, K.; Song, Y. J. Org. Chem. 1995, 60, 1093.
(3) Danheiser, R. L.; Miller, R. F.; Brisbois, R. G.; Park, S. Z. J. Org.
Chem. 1990, 55, 1959.
(4) Yoshida, Y.; Matsumoto, R. H.; Tanabe, Y. Tetrahedron Lett.
2001, 40, 4227. Tanabe, Y.; Yoshida, Y.; Hayashi, R. Tetrahedron Lett.
1997, 38, 8727-8730. Tanabe, Y. Bull. Chem. Soc. Jpn. 1989, 62, 1917.
(13) Nakamura, S.; Hayakawa, T.; Nishi, T.; Watanabe, Y.; Toru,
T. Tetrahedron 2001, 57, 6703.
10.1021/jo048011o CCC: $30.25 © 2005 American Chemical Society
Published on Web 02/24/2005
J. Org. Chem. 2005, 70, 2851-2854
2851

TABLE 1. Benzoylation and Diazo Transfer
a Chromatographed yield. b Chromatographed yield without purification of the intermediate R-benzoylated ester.
SCHEME 1
2852 J. Org. Chem., Vol. 70, No. 7, 2005

(3 × 30 mL). The combined organic extract was dried (MgSO4)
and concentrated. The residue was chromatographed to give
methyl 2-benzoyltetradecanoate 4a (2.70 g, 78% yield) as an
1H), 3.32 (d, J ) 7.5 Hz, 2H), 1.12 (d, J ) 6.4 Hz, 3H), 1.02 (d,
J ) 6.4 Hz, 3H); 13C NMR δ u: 192.9, 167.3, 136.9, 134.7, 33.1
d: 131.9, 127.4, 127.1, 126.9, 125.0, 67.5, 55.0, 19.9, 19.8; IR
1730, 1679, 1597, 1495 cm-1; HRMS calcd for C17H16O3 296.3660,
obsd 296.3663. Anal. Calcd for C17H16O3: C, 77.00; H, 6.80.
Found: C, 77.07; H, 6.89.
1
oil: TLC Rf ) 0.31 (95% H/EtOAc). H NMR δ 7.97 (d, J ) 8.5
Hz, 2H), 7.56 (t, J ) 8.5 Hz, 1H), 7.48 (t, J ) 8.5 Hz, 2H), 4.35
(t, J ) 6.9 Hz, 1H), 3.68 (s, 3H), 2.03 (m, 2H), 1.25 (bs, 20H)
0.88 (t, J ) 6.6 Hz, 3H); 13C NMR δ u: 193.5, 169.0, 131.9, 50.9,
30.3, 28.1, 28.0, 27.9, 27.8, 27.6, 26.1, 21.1 d: 131.9, 127.2, 127.0,
52.5, 12.6; IR 1744, 1689, 1597, 1581, 1448 cm-1; HRMS calcd
tert-Butyl 2-benzoylhydrocinnamate 4i (2.10 g, 67% yield) as
1
an oil:9 TLC Rf ) 0.30 (95% H/EtOAc); H NMR δ 7.95 (d, J )
8.4 Hz, 2H), 7.53 (d, J ) 7.3 Hz, 1H), 7.43 (t, J ) 8.4 Hz, 2H),
7.17-7.26 (m, 5H), 4.51 (t, J ) 7.2 Hz, 1H), 3.29 (d, J ) 7.2 Hz,
2H), 1.28 (s, 9H); 13C NMR δ u: 193.3, 166.9, 137.1, 134.9, 80.5,
33.0 d: 131.8, 127.5, 127.1, 127.0, 125.0, 55.7, 26.2; IR 1728,
1686, 1597, 1495 cm-1; HRMS calcd for C20H22O3 310.3929, obsd
310.3930. Anal. Calcd for C20H22O3: C, 77.39; H, 7.14. Found:
C, 77.45; H, 7.19.
for C22H34O3 346.5102, obsd 346.5114. Anal. Calcd for C22
H34O3: C, 76.26; H, 9.89. Found: C, 76.30; H, 9.96.
-
Methyl 2-benzoylundecanoate 4b (2.65 g, 87% yield) as an
1
oil: TLC Rf ) 0.29 (95% H/EtOAc); H NMR δ 7.98 (d, J ) 7.2
Hz, 2H), 7.59 (t, J ) 7.2 Hz, 1H), 7.48 (t, J ) 7.2 Hz, 2H), 4.33
(t, J ) 7.2 Hz, 1H), 3.67 (s, 3H), 2.00 (m, 2H), 1.24 (s, 14H),
0.87 (t, J ) 6.4 Hz, 3H); 13C NMR δ u: 193.6, 169.0, 134.7, 50.8,
30.3, 27.9, 27.8, 27.7, 27.6, 26.1, 21.1 d: 131.9, 127.2, 127.1,
127.0, 126.5, 52.4, 12.5; HRMS calcd for C19H28O3 304.4295, obsd
304.4297. Anal. Calcd for C19H28O3: C, 74.96; H, 9.27. Found:
C, 74.99; H, 9.29.
Diazo Transfer. 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU,
0.153 mL, 1.0 mmol) was added over 30 min to a solution of the
benzoylated ester (4a, 346 mg, 1 mmol) and 4-acetoamidoben-
zenesulfonyl azide (248 mg, 1.0 mmol) in 10 mL of dry CH3CN
at 0 °C. After the initial exotherm had subsided, additional
4-acetoamidobenzenesulfonyl azide (124 mg, 0.5 mmol) and DBU
(0.076 mL, 0.5 mmol) were added over 30 min. After an
additional 30 min, the mixture was partitioned between water
and EtOAc (3 × 30 mL). The combined organic extract was dried
(MgSO4) and concentrated. The residue was chromatographed
to give methyl 2-diazotetradecanoate 2a (228 mg, 85% yield) as
a yellow oil:1 TLC Rf ) 0.37 (95% H/EtOAc); 1H NMR δ 3.76 (s,
3H), 2.30 (t, 2H, J ) 7.4 Hz), 1.53-1.44 (m, 2H), 1.25 (s, 20 H),
0.88 (t, J ) 6.6 Hz, 3H); 13C NMR δ u: 168.0, 31.9, 29.6, 29.5,
29.3, 29.2, 29.0, 28.7, 27.5, 23.0, 22.6 d: 51.7, 14.0; IR 1702, 1698,
1438 cm-1; HRMS calcd for C15H28O2N2 268.3995 (240.3861 loss
N2), obsd 240.3862. Anal. Calcd for C15H28O2N2: C, 67.13; H,
10.52. Found: C, 67.15; H, 10.55.
Methyl 2-diazoundecanoate 2b (179 mg, 79% yield) as a yellow
oil:5 TLC Rf ) 0.35 (95% H/EtOAc); 1H NMR δ 3.76 (s, 3H), 2.30
(t, 2H, J ) 7.4 Hz), 1.53-1.44 (m, 2H), 1.25 (s, 12H), 0.88 (t, J
) 6.6 Hz, 3H); 13C NMR δ u: 166.5, 30.3, 27.9, 27.7, 27.2, 26.0,
21.4, 21.1 d: 50.2, 12.5; HRMS calcd for C12H22O2N2 226.3189
(198.3055 loss N2), obsd 198.3056. Anal. Calcd for C12H22O2N2:
C, 63.69; H, 9.80. Found: C, 63.72; H, 9.88.
Methyl 2-diazooctanoate 2c (151 mg, 82% yield) as a yellow
oil. TLC: Rf ) 0.32 (95% H/EtOAc); 1H NMR δ 3.76 (s, 3H), 2.30
(t, 2H, J ) 7.4 Hz), 1.49 (m, 2H), 1.32 (m, 6H), 0.89 (t, J ) 6.6
Hz, 3H); 13C NMR δ u: 29.9, 26.8, 26.0, 21.5, 21.0 d: 50.3, 12.5;
HRMS calcd for C9H16O2N2 184.2382 (156.2248 loss N2), obsd
156.2252. Anal. Calcd for C9H16O2N2: C, 58.67;, H, 8.75.
Found: C, 58.68; H, 8.77.
Methyl 2-diazoheptanoate 2d (143 mg, 84% yield) as a yellow
oil: TLC Rf ) 0.30 (95% H/EtOAc); 1H NMR δ 3.75 (s, 3H), 2.30
(t, 2H, J ) 7.4 Hz), 1.53-1.42 (m, 2H), 1.25 (s, 4H), 0.86 (t, J )
6.6 Hz, 3H); 13C NMR δ u: 168.1, 31.9, 29.1, 22.0, 21.5, d: 52.3,
14.3; HRMS calcd for C8H14O2N2 170.2114 (142.1980 loss N2),
obsd 142.1981. Anal. Calcd for C8H14O2N2: C, 56.45; H, 8.29.
Found: C, 56.49; H, 8.37.
Methyl 2-diazohexanoate 2e (151 mg, 84% yield) as a yellow
oil: TLC Rf ) 0.28 (95% H/EtOAc); 1H NMR δ 3.76 (s, 3H), 2.31
(t, 2H, J ) 7.4 Hz), 1.58-1.31 (m, 4H), 0.93 (t, J ) 6.6 Hz, 3H);
13C NMR δ u: 28.1, 21.2, 20.3, d: 50.3, 12.1; HRMS Calcd for
C7H12O2N2 156.1845 (128.1711 loss N2), obsd 128.1716. Anal.
Calcd for C7H12O2N2: C, 53.83; H, 7.74. Found: C, 53.88; H,
7.81.
Methyl 2-diazohydrocinnamate 2f (160 mg, 84% yield) as a
yellow oil:7 TLC Rf ) 0.31 (95% H/EtOAc); 1H NMR δ 7.22-
7.35 (m, 5H), 3.78 (s, 3H), 3.63 (s, 2H); 13C NMR δ u: 164.2,
135.6, 27.8 d: 127.3, 126.8, 126.4, 125.6, 50.5; IR 1730, 1598,
1495, 1453 cm-1; HRMS calcd for C10H10O2N2 190.2016 (162.1882
loss N2), obsd 162.1884. Anal. Calcd for C10H10O2N2: C, 63.15;
H, 5.30. Found: C, 63.17; H, 5.37.
Ethyl 2-diazohydrocinnamate 2g (165 mg, 81% yield) as a
yellow oil:7 TLC Rf ) 0.33 (95% H/EtOAc); 1H NMR δ 7.22-
7.35 (m, 5H), 4.24 (q, J ) 7.2 Hz, 2 H) 3.63 (s, 2H), 1.28 (d, J )
7.2 Hz, 3H); 13C NMR δ u: 163.3, 135.7, 59.4, 27.8 d: 127.2,
126.8, 126.4, 125.6, 13.0; HRMS calcd for C11H12O2N2 204.2285
Methyl 2-benzoyloctanoate 4c (2.20 g, 84% yield) as an oil:
1
TLC Rf ) 0.27 (95% H/EtOAc); H NMR δ 7.98 (d, J ) 7.2 Hz,
2H), 7.59 (t, J ) 7.2 Hz, 1H), 7.49 (t, J ) 7.2 Hz, 2H), 4.33 (t, J
) 7.2 Hz, 1H), 3.68 (s, 3H), 2.00 (m, 2H), 1.29 (s, 8H) 0.86 (t, J
) 6.4 Hz, 3H); 13C NMR δ u: 193.7, 169.0, 134.7, 50.8, 29.9,
27.6, 27.5, 26.0, 20.9 d: 132.0, 127.2, 127.1, 127.0, 52.5, 12.5;
HRMS calcd for C16H22O3 262.3489, obsd 262.3490. Anal. Calcd
for C16H22O3: C, 73.25; H, 8.45. Found: C, 73.28; H, 8.46.
Methyl 2-benzoylheptanoate 4d (2.31 g, 93% yield) as an oil:
1
TLC Rf ) 0.25 (95% H/EtOAc); H NMR δ 7.99 (d, J ) 7.2 Hz,
2H), 7.58 (t, J ) 7.2 Hz, 1H), 7.49 (t, J ) 7.2 Hz, 2H), 4.32 (t, J
) 7.2 Hz, 1H), 3.68 (s, 3H), 2.03 (m, 2H), 1.31 (s, 6H) 0.87 (t, J
) 6.4 Hz, 3H); 13C NMR δ u: 193.7, 169.0, 134.6, 50.9, 30.0,
27.5, 25.8, 20.8 d: 131.9, 127.2, 127.0, 52.5, 12.4; HRMS calcd
for C15H20O3 248.3220, obsd 248.3221. Anal. Calcd for C15
20O3: C, 72.55; H, 8.12. Found C, 72.56; H, 8.14.
Methyl 2-benzoylhexanoate 4e (2.11 g, 90% yield) as an oil:
-
H
1
TLC Rf ) 0.23 (95% H/EtOAc); H NMR δ 7.98 (d, J ) 7.2 Hz,
2H), 7.56 (t, J ) 7.2 Hz, 1H), 7.48 (t, J ) 7.2 Hz, 2H), 4.34 (t, J
) 7.2 Hz, 1H), 3.67 (s, 3H), 2.02 (m, 2H), 1.34 (s, 4H), 0.90 (t, J
) 6.4 Hz, 3H); 13C NMR δ u: 193.7, 168.9,134.6, 50.8, 28.2, 27.3,
21.0 d: 131.9, 127.2, 127.0, 52.4, 12.2; HRMS calcd for C14H18O3
234.2951, obsd 234.2996. Anal. Calcd for C14H18O3: C, 71.77;
H, 7.74. Found C, 71.79; H, 7.79.
Methyl 2-benzoylhydrocinnamate 4f (2.28 g, 85% yield) as an
1
oil:6 TLC Rf ) 0.17 (95% H/EtOAc); H NMR δ 7.95 (d, J ) 8.4
Hz, 2H), 7.53 (d, J ) 7.3 Hz, 1H), 7.45 (t, J ) 8.4 Hz, 2H), 7.21-
7.25 (m, 5H), 4.65 (t, J ) 7.5 Hz, 1H), 3.64 (s, 3H), 3.32 (d, J )
7.5 Hz, 2H); 13C NMR δ u: 192.9, 168.2, 136.8, 134.6, 33.3 d:
132.1, 127.4, 127.2, 127.0, 125.2, 54.4, 51.0; IR 1739, 1686, 1596,
1495, 1448 cm-1; HRMS calcd for C17H16O3 268.3122, obsd
268.3123. Anal. Calcd for C17H16O3: C, 73.25; H, 8.45. Found:
C, 73.28; H, 8.46.
Representative Benzoylation Procedure by Method B.
Titanium tetrachloride (2.87 g, 15 mmol) was added over 30 min
to a solution of benzoyl chloride (4.26 g, 30 mmol), 1g (1.78 g,
10 mmol), and triethylamine (6.13 g, 60 mmol) in 10 mL of dry
CH3CN at 0 °C. The mixture was warmed to reflux for 15 min.
The mixture was cooled and then partitioned between water and
EtOAc (3 × 30 mL). The combined organic extract was dried
(MgSO4) and concentrated. The residue was chromatographed
to give ethyl 2-benzoylhydrocinnamate 4g (2.14 g, 78% yield)
as an oil:8 TLC: Rf ) 0.22 (95% H/EtOAc); 1H NMR δ 7.96 (d, J
) 8.4 Hz, 2H), 7.53 (d, J ) 7.3 Hz, 1H), 7.43 (t, J ) 8.4 Hz, 2H),
7.21-7.25 (m, 5H), 4.63 (t, J ) 7.3 Hz, 1H), 4.08 (q, J ) 7.1 Hz,
2H), 3.32 (d, J ) 7.3 Hz, 2H), 1.10 (t, J ) 7.1 Hz, 3H); 13C NMR
δ u: 192.9, 167.7, 136.9, 134.6, 59.9, 33.2 d: 132.0, 127.4, 127.1,
126.9, 125.1, 54.6, 12.4; IR 1736, 1687, 1597, 1495 cm-1; HRMS
calcd for C18H18O3 282.3391, obsd 283.3398. Anal. Calcd for
C18H18O3: C, 76.57; H, 6.43. Found: C, 76.61; H, 6.54.
Isopropyl 2-benzoylhydrocinnamate 4h (2.01 g, 68% yield) as
1
an oil: TLC Rf ) 0.26 (95% H/EtOAc). H NMR δ 7.96 (d, J )
8.4 Hz, 2H), 7.53 (d, J ) 7.3 Hz, 1H), 7.43 (t, J ) 8.4 Hz, 2H),
7.21-7.25 (m, 5H), 4.94 (m, J ) 7.5 Hz, 1 H) 4.63 (t, J ) 7.5 Hz,
J. Org. Chem, Vol. 70, No. 7, 2005 2853

(176.2151 loss N2), obsd 176.2158. Anal. Calcd for C11H12O2N2:
C, 64.69; H, 5.92. Found: C, 64.77; H, 6.00.
Alkene 7 (160 mg, 99% yield) as an oil: TLC Rf ) 0.32 (95%
H/EtOAc); 1H NMR δ 7.58 (d, J ) 7.4 Hz, 2H), 7.22-7.39 (m,
3H), 6.95 (d, J ) 12.7 Hz, 1H), 5.95 (d, J ) 12.7 Hz, 1H), 3.71
(s, 3H); 13C NMR δ u: 165.1, 133.2, d: 141.8, 128.2, 127.6, 126.5,
117.8, 49.9; IR 1710, 1630, 1430 cm-1; HRMS calcd for C10H10O2
162.1882, obsd 162.1885. Anal. Calcd for C10H10O2: C, 74.06;
H, 6.21. Found: C, 74.11; H, 6.35.
Isopropyl 2-diazohydrocinnamate 2h (181 mg, 83% yield) as
1
a yellow oil: TLC Rf ) 0.36 (95% H/EtOAc); H NMR δ 7.22-
7.35 (m, 5H), 5.11 (m, J ) 6.2 Hz, 1 H) 3.62 (s, 2H), 1.25 (d, J )
6.2 Hz, 6H); 13C NMR δ u: 161.1, 135.8, 27.8 d: 127.2, 126.8,
126.4, 125.5, 66.9, 20.5; HRMS calcd for C12H14O2N2 218.2554
(190.2420 loss N2), obsd 190.2421. Anal. Calcd for C12H14O2N2:
C, 66.04; H, 6.47. Found: C, 66.10; H, 6.53.
Ether 8 (183 mg, 64% yield) as an oil: TLC Rf ) 0.31 (95%
H/EtOAc); 1H NMR δ 7.20-7.36 (m, 5H), 6.77 (d, J ) 2.4 Hz,
4H), 4.47 (dd, J ) 4.5, 6.8 Hz, 1H), 3.77 (s, 3H), 3.76 (s, 3H),
3.13 (dd, J ) 4.5, 13.9 Hz, 1H), 2.96 (dd, J ) 6.8, 13.9 Hz, 1H);
13C NMR δ u: 173.1, 152.2, 148.0, 134.7, 39.1 d: 127.9, 127.8,
127.1, 126.9, 125.4, 114.5, 113.3, 69.7, 54.2, 51.0; IR 1736, 1604,
1510, 1440 cm-1; HRMS calcd for C17H18O4 286.3275, obsd
286.3277. Anal. Calcd for C17H18O4: C, 71.31; H, 6.34. Found:
C, 71.33; H, 6.38.
tert-Butyl 2-diazohydrocinnamate 2i (188 mg, 81% yield) as
1
a yellow oil: TLC Rf ) 0.40 (95% H/EtOAc); H NMR δ 7.22-
7.35 (m, 5H), 3.58 (s, 2H), 1.48 (s, 9H); 13C NMR δ u: 167.4,
136.3, 79.8, 27.8 d: 127.2, 126.8, 126.4, 125.5, 26.8; HRMS calcd
for C13H16O2N2 232.2822 (204.2688 loss N2), obsd 204.2688. Anal.
Calcd for C13H16O2N2: C, 67.22; H, 6.94. Found C, 67.29; H, 7.03.
Amine 5. Methyl 2-diazohydrocinnamate (190 mg, 1.0 mmol)
in 10 mL of dry dichloromethane was added over 1 h to a solution
of rhodium(II) octanoate dimer (0.4 mg, 5 mol %) and p-anisidine
(123 mg, 1.0 mmol) in 10 mL of dry dichloromethane at 25 °C.
The mixture was concentrated and chromatographed to give the
amino ester 5 (239 mg, 84% yield) as an oil: TLC Rf ) 0.12 (95%
H/EtOAc); 1H NMR δ 7.22-7.35 (m, 5H), 6.75 (d, J ) 9.0 Hz,
2H), 6.57 (d, J ) 9.0 Hz, 2H), 4.27 (t, J ) 6.3 Hz, 1H), 3.73 (s,
3H), 3.64 (s, 3H), 4.27 (dd, J ) 3.2, 6.3 Hz, 2H); 13C NMR δ u:
172.4, 151.3, 138.9, 134.9, 37.4 d: 127.7, 126.9, 125.4, 113.7,
113.4, 57.4, 54.1, 50.4; IR 1738, 1619, 1513, 1453 cm-1; HRMS
calcd for C17H19O3N 285.3428, obsd 285.3429. Anal. Calcd for
Sulfide 9 (169 mg, 62% yield) as an oil: TLC Rf ) 0.32 (95%
1
H/EtOAc); H NMR δ 7.16-7.44 (m, 10H), 3.90 (t, J ) 6.4 Hz,
1H), 3.57 (s, 3H), 3.17 (dd, J ) 9.6, 14.2 Hz, 1H), 3.07 (dd, J )
6.4, 14.2 Hz, 1H); 13C NMR δ u: 170.5, 136.1, 36.5 d: 131.7,
131.6, 131.5, 127.9, 127.8, 127.7, 127.6, 127.5, 127.0, 126.9, 126.8,
126.6, 125.5, 125.4, 50.6; IR 1951, 1694, 1583, 1478, 1440 cm-1
;
HRMS calcd for C16H16O2S 272.3678, obsd 272.3682. Anal. Calcd
for C16H16O2S: C, 70.56; H, 5.92. Found: C, 70.61; H, 6.29.
C
17H19O3N: C, 71.56; H, 6.71. Found: C, 71.64; H, 6.76.
Acknowledgment. We thank DuPont Agricultural
Products for financial support of this work.
Amine 6 (228 mg, 76% yield) as an oil: TLC Rf ) 0.19 (95%
H/EtOAc); 1H NMR δ 7.15-7.28 (m, 5H), 6.77 (d, J ) 9.2 Hz,
2H), 6.69 (d, J ) 9.2 Hz, 2H), 4.45 (t, J ) 7.5 Hz, 1H), 3.72 (s,
3H), 3.62 (s, 3H), 3.25 (dd, J ) 7.0, 14.8 Hz, 1H), 3.04 (dd, J )
8.0, 14.0 Hz, 1H), 2.85 (s, 3H); 13C NMR δ u: 170.9, 151.2, 142.8,
136.5, 34.0 d: 127.5, 127.3, 126.9, 125.0, 114.8, 112.9, 64.1, 54.1,
50.2, 32.5; IR 1735, 1604, 1512, 1454 cm-1; HRMS calcd for
Supporting Information Available: General experimen-
tal procedure and spectroscopic data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
C18H21O3N 299.3696, obsd 299.3700. Anal. Calcd for C18
21O3N: C, 72.22. H, 7.07. Found: C, 72.23; H, 7.09.
-
H
JO048011O
2854 J. Org. Chem., Vol. 70, No. 7, 2005