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Determination of the absolute configuration of linear secondary alcohols adopting one enantiomer of the chiral anisotropic reagents, methoxy-(1-and 2-naphthyl)acetic acids
TETRAHEDRON LETTERS Pergamon
Tetrahedron Letters 39 (1998) 8113-8116
Determination of the absolute configuration of linear secondary alcohols adopting one enantiomer of the chiral anisotropic reagents, methoxy(1- and 2-naphthyl)acetic acids Hiroshi Yamase, Takashi Ooi, and Takenori Kusumi* Faculty of Pharmaceutical Sciences Tokushima University Tokushima 770-8505, Japan
Received 11 June 1998; revised 24 August 1998; accepted 28 August 1998
Abstract The absolute configurations of the aliphatic secondary alcohols can be determined by NMR spectroscopy using only one enantiomer of the chiral anisotropic reagents, I N M A and 2NMA.
© 1998 Elsevier Science Ltd. All rights reserved.
Keywords: Alcohols; Configuration; NMR; Stereochemistry
The modified Mosher's method [1] is now worldwidely used for determination of the absolute configuration of secondary alcohols. In the Mosher's and analogous methods, both (R)- and (S)-esters are necessary to obtain AS values. Recently, as a unique countermeasure for this intricacy, Riguera, et al, has proposed the use of a single methoxyphenylacetic ester derivative, the 1H-NMR spectrum of which was recorded at two different temperatures [2]. We have reported that the chiral anisotropic reagents, 1- and 2-naphthylmethoxyacetic acids (1NMA and 2NMA), show anisotropic effect larger than MTPA [3, 4]. This extremely large anisotropy of 1NMA and 2NMA led us to the idea that a single enantiomer of these reagents would be enough for determining the absolute configuration of secondary alcohols. We at first considered that the absolute configuration could be determined by subtracting chemical shifts of the NMA ester from those of the original alcohol (A~OH_NMA = ~OH ~NMA)- The A~OH_NM A values obtained 1 for 1NMA and 2NMA esters of (R)-2-octanol are shown in Figure 1. 1 All the NMR spectra (400 MHz) were recorded in CDCI3 at 30 °C. Concentration of the sample was set at 0.1-0.2 M.
0040-4039/98/$ - see front matter © 1998 Elsevier Science Ltd. All rights reserved. PIl: S0040-4039(98)01800-0
8114
.... syn side . . . . . . . .
anti side ....
.... syn side . . . . . . . .
+0.252 +0.413 +0.156 -0.029
+0.4oo
+0.647 i (R)-INMA-- 0 .... anti side ....
+
0
-0.100
.... anti side
.... syn side ....
~
....
!
-0.155.... s y n
side ....
82 +0.023 +0.078 +0.157
|
+0.0s6
I O-(b~-2NMA
O-(S)-INMA
,r"KX.,..x
.... santi side--~. ~
I COOH
_o_
-.f
H
.... syn ~icle ....
2NMA
.~H
",,
COOH
INMA
anti side ....
+0.024 +0.2.59 +0.281 +0~059 -0.056
+0.155
5
-o.. ' 2NMA
0
plane
Figure 1. A~)OH.NMAvalues obtained for (R)-2-octanol are shown. Values larger than 0.08 ppm are shown in bold. The ideal conformationof the (R)-2NMA ester of (R)-2-octanol is described on the right bottom. In the ideal conformation,the naphthyl group directed toward the left side of the plane. Such direction of the naphthyl group is shown in the structures of the NMA esters. In (R)-NMA ester, the protons with large A~OH.NMA values (> +0.08 ppm) distribute on the same side (syn side) of the naphthyl group of NMA. In the case of (S)-NMA ester, however, the protons with large A~OH_NMA values are seen on the opposite side (anti side) to the naphthyl group of NMA as well as syn side. This conflicting results might be due to ignorance of the electronic effect caused by esterification of the alcohol. We next intended to compare the chemical shifts of the NMA ester with those of the acetate. The A~Ac.NMA values (A~Ac-NMA = SAc - 8NMA) obtained for (R)-2-octanol are shown in Figure 2. When the threshold value was set at 0.08 ppm, the protons over the threshold distribute on only syn side of NMA. This indicates that the absolute configuration +0.234
+0.394
+0.264 +0.154
+0.130 4.0.262 +0.067
+0.241
-0.020 4
.
0
.
1
3
+0.006
-
0
.
+0.049 0
0
-0.049
+0.004 +0.191 9
~
( Fi'),,,2NMA--O
(R)-I NMA-- O
+0.026
-0.047
+0.039 +
~ O-- (,S)-INMA
0
40.025 .
0
-0.044
+0.093
~ o - (S)-~MA
Figure 2. A~^c-NMA values obtained for (R)-2-octanol. The values over the threshold value [0.08 ppm] are shown in hold.
8115
can be determined by ASAc-NMA values and setting the threshold at 0.08 ppm. However, this methodology needs two derivatization reactions [acetylation and esterification with (R)- or (S)-NMA], and it does not seem to be more advantageous than the conventional method using e.g. AS = S (R)-2NMA - S (S)-2NMADuring our works on the utility of INMA and 2NMA, a number of IH-NMR data of the acetates of linear and cyclic secondary alcohols have been accumulated, and we have noticed that there was a marked tendency about the chemical shifts of the NMA esters. This led us to establishment of the increment parameters shown in Figure 3. The increment parameters were obtained from the average differences between S(acetate) and S(alcohol) of fifteen linear alcohols including (S)-10-nonacosanol [4]. The AS' value is defined as [AS'= SOH - SNMA + increment], and an example is shown in Figure 4. The protons with AS' values over the threshold(0.08 ppm) distribute only syn side of NMA. OH -0.02
-0.03
(-0.01) -0.02
(-0.02) -0.02
-0.09
(-0.01) -0.03
I
-0 17 _'_
I
(+0.05) [+0.15 +0.08 44.0.04
[
Figure 3. The incrementparameter for the linear alcohols. The values in parenthesis is for the methyl group at the position. These parameters should be used for the protons irrespctive of the direction of the naphthyl group. In case that the protons at ~- or V-positionsappear as nonequibvalent signals, the upper (lower) value in the half parenthesis is used for the proton with a larger (smaller) A~)OH-NMAinstead of the average value. This methodology was applied to other linear alcohols. Figure 5 shows AS' values for the 1NMA and 2NMA esters of 2-butanol, 2-pentanol, 2-bexanol and 3-bexanol. AS' values over +0.306 +0.232
+0.383
+0.196
+0"~
+0.021
+0.239
I
+0.038
4-0.050 +0 016
-0.006
I
(R)-2NMA-- O
4-0.232
-0.
+0.037
+0"
+0.067
+0.174 +0.099
+0-~
IR)-I NMA-- O
+0.024
+0.251
O--(S)-INMA
+0.014
-0.005 -0.032
+0.046
+0.134
• O~(S)-2NMA
Figure 4. A6' values obtained for 1NMA and 2NMA esters of (R)-2-octanol. The values over threshold (0.08 ppm) arc shown in bold.
8116
threshold (0.08 ppm) in all the compounds are found on syn side of the naphthyl group. From these results, we have concluded that the absolute configurations of linear alcohols can be determined by AS' values adopting the increment parameters shown in Figure 3. 1NMA esters
(S)-INMA. (~
(S)-I NMA-- t'l
+0.001 +0.230
+0.021~
O-(S)-INMA
+0.210
+0.029 ~ -0'009 +0"228
~ +0.365 +0.232 +0.014
+
0
~
+0.529 | ~ 0 . 0 3 8 +0.393
+0,204
O--(S)..1NMA
+0.231 +0.031 -0.006
+0.006
n _O-(+0.008 - - | _,, 1NMA
+0383/~
(R)-INMA- O
+0.296
+0.412 +0.180 +0.016
+0.006 _O-(R)-INMA
÷u.t~o
!
$4~
+0.040 -0.001 +0,238 +0.033
+ 0 . 3 ~ (R)-INMA- 0
+0.032 +0.008 40.257 +0.220
2NMA esters
(S)-2NMk _O
-0.042 +0.129 .0.012/~
+0.215 +0.076 -0.014
O-(S)-2NMA +0.082
(S)'2NM.~(~
~ ~ -0.024 / +0.015 -0.056 +0.133 +0.0~
~ ~
O-(R)-2NMA
m
+0.245 +0.089-0.012
0-" (S)-2NMA
+0.098
-0.021
j-
~ +0.271 ~ . ~ .| 0 1 9
+0.149 ./~
/
+0.252 +0.059 -0.012
-0049 ~ -0.028
~-(R)-2NMA
+0.0101+0.286
+0.219~~
(R)-2NMA- O
+0.018 -0.057 + 0 . 1 4 0 -0.016
+ 0 . 2 8 3 ~
(R)-2NMA- O
+0.020 -0.040 +0.131 +0.094
Figure 5. AS' values obtained for the INMA and 2NMA esters of (R)-2-butanol, (S)-2-pentanol, (R)-2-hexanol and (S)-3-hexanol. References
[I] Ohtani I, gusumi T, gashman Y, Kakisawa H. J. Am. Chem. Soc. 1991;113:4092-4096. [2] Latypov Sh. K, Seco J. M, Quifio~ E, Riguera R. J. Am. Chem. Soc. 1998;120:877-882. [3] Takahashi H, Kusumi T, Kan Y, Satake M, Yasumoto T. Tetrahedron Lett. 1996;37:7087-7090. [4] Takahashi H, Kusumi T, Hashimoto T, Asakawa Y. Chemistry Lett. 1994:1093-1094.
Tetrahedron Letters 39 (1998) 8113-8116
Determination of the absolute configuration of linear secondary alcohols adopting one enantiomer of the chiral anisotropic reagents, methoxy(1- and 2-naphthyl)acetic acids Hiroshi Yamase, Takashi Ooi, and Takenori Kusumi* Faculty of Pharmaceutical Sciences Tokushima University Tokushima 770-8505, Japan
Received 11 June 1998; revised 24 August 1998; accepted 28 August 1998
Abstract The absolute configurations of the aliphatic secondary alcohols can be determined by NMR spectroscopy using only one enantiomer of the chiral anisotropic reagents, I N M A and 2NMA.
© 1998 Elsevier Science Ltd. All rights reserved.
Keywords: Alcohols; Configuration; NMR; Stereochemistry
The modified Mosher's method [1] is now worldwidely used for determination of the absolute configuration of secondary alcohols. In the Mosher's and analogous methods, both (R)- and (S)-esters are necessary to obtain AS values. Recently, as a unique countermeasure for this intricacy, Riguera, et al, has proposed the use of a single methoxyphenylacetic ester derivative, the 1H-NMR spectrum of which was recorded at two different temperatures [2]. We have reported that the chiral anisotropic reagents, 1- and 2-naphthylmethoxyacetic acids (1NMA and 2NMA), show anisotropic effect larger than MTPA [3, 4]. This extremely large anisotropy of 1NMA and 2NMA led us to the idea that a single enantiomer of these reagents would be enough for determining the absolute configuration of secondary alcohols. We at first considered that the absolute configuration could be determined by subtracting chemical shifts of the NMA ester from those of the original alcohol (A~OH_NMA = ~OH ~NMA)- The A~OH_NM A values obtained 1 for 1NMA and 2NMA esters of (R)-2-octanol are shown in Figure 1. 1 All the NMR spectra (400 MHz) were recorded in CDCI3 at 30 °C. Concentration of the sample was set at 0.1-0.2 M.
0040-4039/98/$ - see front matter © 1998 Elsevier Science Ltd. All rights reserved. PIl: S0040-4039(98)01800-0
8114
.... syn side . . . . . . . .
anti side ....
.... syn side . . . . . . . .
+0.252 +0.413 +0.156 -0.029
+0.4oo
+0.647 i (R)-INMA-- 0 .... anti side ....
+
0
-0.100
.... anti side
.... syn side ....
~
....
!
-0.155.... s y n
side ....
82 +0.023 +0.078 +0.157
|
+0.0s6
I O-(b~-2NMA
O-(S)-INMA
,r"KX.,..x
.... santi side--~. ~
I COOH
_o_
-.f
H
.... syn ~icle ....
2NMA
.~H
",,
COOH
INMA
anti side ....
+0.024 +0.2.59 +0.281 +0~059 -0.056
+0.155
5
-o.. ' 2NMA
0
plane
Figure 1. A~)OH.NMAvalues obtained for (R)-2-octanol are shown. Values larger than 0.08 ppm are shown in bold. The ideal conformationof the (R)-2NMA ester of (R)-2-octanol is described on the right bottom. In the ideal conformation,the naphthyl group directed toward the left side of the plane. Such direction of the naphthyl group is shown in the structures of the NMA esters. In (R)-NMA ester, the protons with large A~OH.NMA values (> +0.08 ppm) distribute on the same side (syn side) of the naphthyl group of NMA. In the case of (S)-NMA ester, however, the protons with large A~OH_NMA values are seen on the opposite side (anti side) to the naphthyl group of NMA as well as syn side. This conflicting results might be due to ignorance of the electronic effect caused by esterification of the alcohol. We next intended to compare the chemical shifts of the NMA ester with those of the acetate. The A~Ac.NMA values (A~Ac-NMA = SAc - 8NMA) obtained for (R)-2-octanol are shown in Figure 2. When the threshold value was set at 0.08 ppm, the protons over the threshold distribute on only syn side of NMA. This indicates that the absolute configuration +0.234
+0.394
+0.264 +0.154
+0.130 4.0.262 +0.067
+0.241
-0.020 4
.
0
.
1
3
+0.006
-
0
.
+0.049 0
0
-0.049
+0.004 +0.191 9
~
( Fi'),,,2NMA--O
(R)-I NMA-- O
+0.026
-0.047
+0.039 +
~ O-- (,S)-INMA
0
40.025 .
0
-0.044
+0.093
~ o - (S)-~MA
Figure 2. A~^c-NMA values obtained for (R)-2-octanol. The values over the threshold value [0.08 ppm] are shown in hold.
8115
can be determined by ASAc-NMA values and setting the threshold at 0.08 ppm. However, this methodology needs two derivatization reactions [acetylation and esterification with (R)- or (S)-NMA], and it does not seem to be more advantageous than the conventional method using e.g. AS = S (R)-2NMA - S (S)-2NMADuring our works on the utility of INMA and 2NMA, a number of IH-NMR data of the acetates of linear and cyclic secondary alcohols have been accumulated, and we have noticed that there was a marked tendency about the chemical shifts of the NMA esters. This led us to establishment of the increment parameters shown in Figure 3. The increment parameters were obtained from the average differences between S(acetate) and S(alcohol) of fifteen linear alcohols including (S)-10-nonacosanol [4]. The AS' value is defined as [AS'= SOH - SNMA + increment], and an example is shown in Figure 4. The protons with AS' values over the threshold(0.08 ppm) distribute only syn side of NMA. OH -0.02
-0.03
(-0.01) -0.02
(-0.02) -0.02
-0.09
(-0.01) -0.03
I
-0 17 _'_
I
(+0.05) [+0.15 +0.08 44.0.04
[
Figure 3. The incrementparameter for the linear alcohols. The values in parenthesis is for the methyl group at the position. These parameters should be used for the protons irrespctive of the direction of the naphthyl group. In case that the protons at ~- or V-positionsappear as nonequibvalent signals, the upper (lower) value in the half parenthesis is used for the proton with a larger (smaller) A~)OH-NMAinstead of the average value. This methodology was applied to other linear alcohols. Figure 5 shows AS' values for the 1NMA and 2NMA esters of 2-butanol, 2-pentanol, 2-bexanol and 3-bexanol. AS' values over +0.306 +0.232
+0.383
+0.196
+0"~
+0.021
+0.239
I
+0.038
4-0.050 +0 016
-0.006
I
(R)-2NMA-- O
4-0.232
-0.
+0.037
+0"
+0.067
+0.174 +0.099
+0-~
IR)-I NMA-- O
+0.024
+0.251
O--(S)-INMA
+0.014
-0.005 -0.032
+0.046
+0.134
• O~(S)-2NMA
Figure 4. A6' values obtained for 1NMA and 2NMA esters of (R)-2-octanol. The values over threshold (0.08 ppm) arc shown in bold.
8116
threshold (0.08 ppm) in all the compounds are found on syn side of the naphthyl group. From these results, we have concluded that the absolute configurations of linear alcohols can be determined by AS' values adopting the increment parameters shown in Figure 3. 1NMA esters
(S)-INMA. (~
(S)-I NMA-- t'l
+0.001 +0.230
+0.021~
O-(S)-INMA
+0.210
+0.029 ~ -0'009 +0"228
~ +0.365 +0.232 +0.014
+
0
~
+0.529 | ~ 0 . 0 3 8 +0.393
+0,204
O--(S)..1NMA
+0.231 +0.031 -0.006
+0.006
n _O-(+0.008 - - | _,, 1NMA
+0383/~
(R)-INMA- O
+0.296
+0.412 +0.180 +0.016
+0.006 _O-(R)-INMA
÷u.t~o
!
$4~
+0.040 -0.001 +0,238 +0.033
+ 0 . 3 ~ (R)-INMA- 0
+0.032 +0.008 40.257 +0.220
2NMA esters
(S)-2NMk _O
-0.042 +0.129 .0.012/~
+0.215 +0.076 -0.014
O-(S)-2NMA +0.082
(S)'2NM.~(~
~ ~ -0.024 / +0.015 -0.056 +0.133 +0.0~
~ ~
O-(R)-2NMA
m
+0.245 +0.089-0.012
0-" (S)-2NMA
+0.098
-0.021
j-
~ +0.271 ~ . ~ .| 0 1 9
+0.149 ./~
/
+0.252 +0.059 -0.012
-0049 ~ -0.028
~-(R)-2NMA
+0.0101+0.286
+0.219~~
(R)-2NMA- O
+0.018 -0.057 + 0 . 1 4 0 -0.016
+ 0 . 2 8 3 ~
(R)-2NMA- O
+0.020 -0.040 +0.131 +0.094
Figure 5. AS' values obtained for the INMA and 2NMA esters of (R)-2-butanol, (S)-2-pentanol, (R)-2-hexanol and (S)-3-hexanol. References
[I] Ohtani I, gusumi T, gashman Y, Kakisawa H. J. Am. Chem. Soc. 1991;113:4092-4096. [2] Latypov Sh. K, Seco J. M, Quifio~ E, Riguera R. J. Am. Chem. Soc. 1998;120:877-882. [3] Takahashi H, Kusumi T, Kan Y, Satake M, Yasumoto T. Tetrahedron Lett. 1996;37:7087-7090. [4] Takahashi H, Kusumi T, Hashimoto T, Asakawa Y. Chemistry Lett. 1994:1093-1094.