Chemistry Letters Vol.32, No.3 (2003)
301
Table 3. Esterification of benzoic acid using Ph2PNMe2 and various secondary
alcohols
alcohol (5.0 mmol) in THF (18 mL) was dropped a solution of
1.56 M nBuLi /Hexane (5.0 mmol) at 0 ꢁC under argon atmo-
sphere. After the solution was stired at room temperature for 1.0 h,
Ph2PCl (5.0 mmol) was added at 0 ꢁC. The reaction mixture was
stirred for 1.0 h at room temperature and was concentrated in
vacuo. After the residue was diluted with the mixed solution of
hexane (8 mL) and ethyl acetate (1 mL), lithium chloride etc. were
removed by filtration through celite (3.0 g) after passing through
alumina (basic) (Wako pure chemical industries, LTD) (20 g).
The diluted solution was concentrated in vacuo, and crude but
virtually pure alkoxydiphenylphosphines were obtained. To a
mixture of carboxylic acid (0.60 mmol) and DMBQ (0.60 mmol)
under argon atmosphere was added a solution of the above crude
alkoxydiphenylphosphine in dichloromethane (0.50 mL) under
the conditions shown in Table 4. After completion of the reaction
(detected by TLC), it was quenched with water and the mixture
was extracted with dichloromethane. The organic layers were
dried over anhydrous sodium sulfate, filtered and concentrated.
The crude product was purified by preparative TLC to afford the
corresponding carboxylic esters.
Thus, a new and efficient method for the preparation of
carboxylic esters from various primary, bulky secondary and
tertiary alcohols and carboxylic acids was established and the
corresponding carboxylic acid esters were afforded in good to
high yields by way of a new-type oxidation-reduction condensa-
tion using in situ formed alkoxydiphenylphosphines, DMBQ, and
carboxylic acids. Alkoxyphosphines were prepared in situ from
Ph2PNMe2 and primary or secondary alcohols, and primary,
secondary or tertiary alkoxydiphenylphosphines were formed
alternatively in situ by initially treating alcohols with nBuLi and
then to add Ph2PCl. In addition, the corresponding carboxylic
acid alkyl esters were obtained with perfect inversion of
stereochemistry by SN2 replacement in the cases of using chiral
secondary alcohols. Further study on this type of condensation
reaction is now in progress.
PhCOOH (1.0 equiv.)
DMBQ (1.0 equiv.)
R'OH
(1.1 equiv.)
O
Ph2PNMe2
(1.1 equiv.)
Ph2POR'
ClCH2CH2Cl
rt, 1.0 h
Ph
OR'
ClCH2CH2Cl
100 oC,7.0 h
R'OH
iPrOH
R'OH
OH
α
Entry
1
Yield /% Entry
Yield /%
D
94d
24
D
= +26.6
α
5a
94
(c3.08, EtOH)
Ph
Et
Me
OH
2
95
OH
21
D
= -35.3
α
tBu
88
6b
7c
(c1.10, CHCl3)
Me
OH
96
94
3
Ph
Ph
OH
OH
23
D
Ph
= +92.0
α
88e
4
(c1.16, C6H6)
25
a
½ꢀ
¼ À28:7 (c1:02, EtOH) (preparation from PhCOCl, Et3N,
D
alcohol).8 In addition, Daicel Chiralcel OD column was used for chiral
HPLC analysis.
22
b
½ꢀ
¼ þ34:6 (c1:16, CHCl3) (preparation from PhCOCl, Et3N,
D
alcohol).9
24
c
½ꢀ
¼ À93:5 (c1:23, C6H6) (preparation from PhCOCl, Et3N, alco-
D
hol). Diastereoselectivities determined by 1H NMR spectroscopy.10 Also,
intermediate L-menthoxydiphenylphosphine was prepared by mixture
of L-menthol with Ph2PNMe2 stirred for 10 h at 100 ꢁC.
d90%Yieldby Mitsunobureaction.11 e27%Yieldby Mitsunobureaction.11
hols to form alkoxydiphenylphosphine did not take place at all.
Then, preparation of the phosphine from Ph2PCl and alcohols
n
using BuLi was tried according to Evans’s procedure.12 The
esterification of various in situ formed tertiary and secondary
alkoxy diphenylphosphines having sterically hindered bulky
groups with benzoic acid was examined under the above
conditions (Table 4). When tertiary alcohols were used, the
desired esters were obtained in good yields under the conditions
shown in Table 4(Entries 1–7). Whereas the corresponding esters
were afforded in high yields with perfect inversion of stereo-
chemistry with secondary alcohols by SN2 replacement (Entries
8–9). According to this procedure, primary alcohol gave the
corresponding alkoxydiphenylphosphine smoothly, therefore,
the desired ester was afforded in high yield by one-pot procedure
by treating with benzoic acid (Entry 11).
This study was supported in part by the Grand of the 21st
Century COE Program, Ministry of Education, Culture, Sports,
Science, and Technology (MEXT).
Typical experimental procedure is as follows: to a solution of
Table 4. Esterification of benzoic acid using nBuLi and various bulky
secondary and tertiary alcohols
References
1
2
E. Haslam, Tetrahedron, 36, 2409 (1980).
For examples; a) D. Karmakar and P. J. Das, Synth. Commun., 31, 535 (2001). b) J.
E. Kaminska, Z. J. Kaminski, and J. Gora, Synthesis, 1999, 593. c) H. Zhao, A.
Pendri, and R. B. Greenwald, J. Org. Chem., 63, 7559 (1998). d) A. G. M. Barrett,
D. C. Braddock, R. A. James, N. Koike, and P. A. Procopiou, J. Org. Chem., 63,
6273 (1998).
nBuLi/Hexane
O
PhCOOH (1.0 equiv.)
Ph2PCl
R'OH
Ph2POR'
(crude)
Ph
OR'
DMBQ (1.0 equiv.)
CH2Cl2
THF
0-rt oC, 1.0 h
3
4
5
T. Mukaiyama, T. Shintou, and W. Kikuchi, Chem. Lett., 2002, 1126.
T. Shintou, W. Kikuchi, and T. Mukaiyama, Chem. Lett., 32, 22 (2003).
G. M. Kosolapoff and L. Maier, in ‘‘Organic Phosphorus Compounds,’’ Wiley &
Sons, New York (1973), Vol. 4, p 504.
Entry
R0OH
tBuOH
Et3COH
Ph2POR0 /equiv. Condition Yield /%
1
2
3
4
5
1.2
1.2
1.2
1.2
1.2
1.2
1.5
1.1
1.1
reflux, 6.0 h
reflux, 6.0 h
rt, 15 h
rt, 6.0 h
reflux, 15 h
rt, 15 h
reflux, 3.0 h
rt, 3.0 h
rt, 1.0 h
79
72
81
81
83
82
78
86
93
6
7
P. Denis, A. Mortreux, F. Petit, G. Buono, and G. Peiffer, J. Org. Chem., 49, 5274
(1984).
PhC(CH3)2OH
PhCH2C(CH3)2OH
1-Adamantanol
1-Methylcyclopentanol
1-Methylcyclohexanol
L-(À)-Menthol
R-(+)-Phenylethanol
trans-2-Phenyl-
1-cyclohexanol
BnOH
Dimethylamine was passed into a solution of Ph2PCl in Et2O at 0 ꢁC. Distillation
gave Ph2PNMe2, Yield 87% (b.p. 129 ꢁC/0.7 Pa). See: K. Diemert, G. Hein, A.
Janssen, and W. Kuchen, Phosphorus, Sulfur Silicon Relat. Elem., 53, 339 (1990).
K. Kabuto, M. Imuta, E. S. Kempner, and H. Ziffer, J. Org. Chem., 43, 2357
(1978).
6
8
9
7
8a
9b
M. Node, K. Nishide, Y. Shigeta, H. Shiraki, and K. Obata, J. Am. Chem. Soc., 122,
1927 (2000).
10c
(11
1.1
1.1
rt, 3.0 h
rt, 1.0 h
85
10 a) A. M. Barrett, D. C. Braddock, R. A. James, N. Koike, and P. A. Procopiou, J.
Org. Chem., 63, 6273 (1998). b) J. E. Kaminska, Z. J. Kaminski, and J. Gora,
Synthesis, 1999, 593.
98)
11 a) O. Mitsunobu, Synthesis, 1981, 1. b) S. F. Martin and J. A. Dodge, Tetrahedron
Lett., 32, 3017 (1991).
12 D. A. Evans, K. R. Campos, J. S. Tedrow, F. E. Michael, and M. R. Gagne, J. Am.
Chem. Soc., 122, 7905 (2000).
14
a
½ꢀ
¼ þ92:4 (c1:22, C6H6). The corresponding ester was obtained
D
with perfect inversion of stereochemistry by of SN2 replacement.
b
23
½ꢀ
¼ þ27:3 (c1:22, EtOH). c58% Yield Mitsunobu reaction.11
D