On the specific rotation of deuterium-containing isotopomers of 2-dimethylaminocyclohexyl-1-trimethylammonium iodide

Article abstract of DOI:10.1002/jlcr.1036

The specific rotation of a variety of differential isotopomers is reported. The difference in their specific rotation appears to be greater than their percentage mass difference and each isotopomer seems to rotate (the plane of) plane-polarized light differently. Copyright

Full text of DOI:10.1002/jlcr.1036

JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS
J Label Compd Radiopharm 2006; 49: 153–161.
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jlcr.1036
Research Article
On the specific rotation of deuterium-containing
isotopomers of 2-dimethylaminocyclohexyl-1-
trimethylammonium iodide
Gregory S. Coumbarides, Marco Dingjan, Jason Eames* and
Michael J. Suggate
Department of Chemistry, Queen Mary, University of London, London E1 4NS, UK
Summary
The specific rotation of a variety of differential isotopomers is reported. The difference
in their specific rotation appears to be greater than their percentage mass difference
and each isotopomer seems to rotate (the plane of) plane-polarized light
differently. Copyright # 2005 John Wiley & Sons, Ltd.
Key Words: deuterium; isotopomers; optical rotation; quasi-enantiomeric; specific
rotation
Introduction
Compounds that are chiral by virtue of deuterium labelling are known to have
small but significant specific rotations, f½aꢀTDg, in the order ꢁ 0.5–28.1–3, y
However, in certain cases, the specific rotation can be extremely high (ꢂ3678)4
due to a cooperative deuterium effect, and in other cases undetectable.5 The
relative conformation of certain deuteriated substrates has been shown to have
a remarkable influence on their specific rotation6 and this has been
documented in a number of other studies.4
The magnitude of rotation (of the plane) of plane-polarized light has been
shown to be influenced by optically active chromophores, such as polarizable
aromatic rings.7,8 Whilst a C–D bond is shorter, and consequently has lower
polarizability than its parent C–H bond;1b the result of which may give rise to
*Correspondence to: J. Eames, Department of Chemistry, University of Hull, Cottingham Road, Kingston
upon Hull, HU6 7RX UK. E-mail: j.eames@hull.ac.uk
y Liquid crystals have been shown to give increased sensitivity for molecules that owe their chirality due to
isotopic substitution.2
Contract/grant sponsor: Queen Mary, University of London
Contract/grant sponsor: GOSS Scientific Instruments Ltd
Copyright # 2005 John Wiley & Sons, Ltd.
Received 17 October 2005
Revised 6 November 2005
Accepted 12 November 2005

154
G. S. COUMBARIDES ET AL.
lower specific rotations for deuterium-containing chiral isotopomers.
Within the literature, it is apparent that very little attention has been focussed
on this area. Most notably, Paquette and Mason have observed a decrease in
specific rotation of deuterium-labelled apoborenes relative to their unlabelled
variants.1b Whereas, Meyer and Lobo have reported a 3% reduction in the
magnitude of the peak and trough (in the Cotton Effect) for a series of
camphor D-labelled isotopomers relative to their non-labelled parent
substrates.9 Closer inspection of the literature has revealed conflicting views;
in some cases a moderate decrease in the specific rotation for a deuterium-
containing isotopomer has been shown,10,11 whereas, others have shown a
marginal increase in specific rotation.10 By comparison, both unlabelled and
D-labelled chiral isotopomers have been reported to have similar optical
rotatory dispersion properties.7,12, z Within the literature, it is evident that a
significant amount of attention has been focussed on probing differential
isotopomers using vibrational optical activity13 and studying their theoretical
optical rotation.14, }
Results and discussion
We have recently become interested in the synthesis of enantiomerically pure
symmetrically N,N0-tetra-substituted 1,2-diamines, like (R,R)-2, through
sequential alkylation of 1,2-diaminocyclohexane (R,R)-1 mediated by lithium
hydroxide monohydrate as the stoichiometric base (Scheme 1).15 This
methodology has been shown to be particularly versatile for SN2 active
electrophiles, which are structurally related to benzyl bromide and allyl
bromide.16 Within a series of reports, we have extended this methodology
towards related unsymmetrically N,N0-tetra-substituted 1,2-diamines derived
from symmetrically N,N0-di-substituted 1,2-diamines.17 Under these condi-
tions, formation of the corresponding ammonium salt(s) through simple
quaternatization of the resulting tertiary 1,2-diamine does not occur.18
In an attempt to probe the scope and limitation of this methodology,15–17,19
we were interested in the use of methyl iodide as our SN2 active electrophile.
Using our standard protocol,15 addition of five equivalents of methyl iodide to
a stirred solution of 1,2-diaminocyclohexane (R,R)-1 and lithium hydroxide
monohydrate (four equivalents) in dichloromethane, gave exclusively the
ammonium iodide (R,R)-3 in 87% yield (Scheme 1). This process must proceed
via methylation of the corresponding tetramethyl-1,2-diamino cyclohexane
(R,R)-4. This pathway was shown to be particularly efficient since addition of
methyl iodide to a stirred solution of tetramethyl-1,2-diaminocyclohexane
z By using optical rotatory dispersion.12
} For a quantum mechanical account of optical activity, see Rosenfeld.14c
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SPECIFIC ROTATION OF DEUTERIUM-CONTAINING ISOTOPOMERS
155
Scheme 1.
(R,R)-4 in dichloromethane gave, the required ammonium iodide (R,R)-3 in
96% yield (Scheme 2).
We next focussed our attention on synthesizing a series of non-racemizable
deuterium-containing isotopomers (R,R)-3-d3, d6, d9 and d15 based on the
parent ammonium iodide (R,R)-3 in attempt to probe their specific rotations.
We were interested in these particular derivatives due to their ease of synthesis,
configurational stability, rich abundance of deuterium atoms and differential
molecular masses. We first synthesized the isotopomeric ammonium iodides
(R,R)-3-d3, (R,R)-3-d9, (R,R)-3-d15, and (R,R)-3-d6 by simple addition of
trideuteriomethyl iodide to the corresponding 1,2-diamines (R,R)-4, (R,R)-5
and (R,R)-1, respectively (Scheme 3), and by addition of methyl iodide to the
N,N0-di-(trideuteriomethyl)-diaminocyclohexane (R,R)-9-d6. These reactions
proceeded efficiently giving a wide range of deuterium-containing enantio-
merically pure isotopomeric ammonium iodides (R,R)-3-d3, (R,R)-3-d6,
(R,R)-3-d9 and (R,R)-3-d15 in good yields (Scheme 3). By 13C NMR
spectroscopy, it is interesting to note the relative C–N chemical shifts for
these parent isotopomers; the 13C NMR chemical shift for the CH3–N+ signal
appears downfield relative to the CH–N signal}e.g. for (R,R)-3-d3, the
chemical shifts for C–N+, CH–N, CH3–N+ and CH3–N appear at 71.8, 64.5,
53.8 and 40.0 ppm, respectively.
With these isotopomers in hand, it was interesting to discover that their
specific rotations differed considerably (Table 1). We had initially expected the
Scheme 2.
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G. S. COUMBARIDES ET AL.
Scheme 3.
specific rotations to be marginally lower on increasing deuterium incorpora-
tion due to its dependence on concentration (g/ml)},k by assuming each
} Based on the difference in molarity, the specific rotation of a deuterium-labelled isotopomer is equal to ½aꢀDT
(of the unlabelled substrate) ꢃ (Md0/Mdn), where Md0 is the molecular mass of the unlabelled substrate and
Mdn is the molecular mass of the D-labelled substrate. From this, the assumed specific rotation for 3-d3,
3-d6, 3-d9 and 3-d15 is ꢂ42.37, ꢂ41.97, ꢂ41.60 and ꢂ40.8, respectively (based on the unlabelled ammonium
iodide 3-d0) and ꢂ42.14, ꢂ41.45, ꢂ40.18 and ꢂ39.59, respectively (based on the unlabelled ammonium ion
itself).
k By assuming the rotation of the plane of plane-polarized light is unaltered by the presence of an isotopic
label (or the change is negligible); the observed rotation of a labelled substrate can approximated to
aobsðLÞ ¼ aobsðUÞ ꢃ RMMU=RMML when all other variables are constant. Obviously, ½aꢀTD ðlabelledÞ ¼
a
obsðLÞ=c1l1 and ½aꢀTD ðunlabelledÞ ¼ aobsðUÞ=c2l2. However, l1 ¼ l2 for the same polarimeter cell, and
c1 ¼ gðLÞ=mlðLÞ and c2 ¼ gðuÞ=mlðuÞ. If we assume that mlðLÞ ¼ mlðUÞ, and gðLÞ ¼ gðUÞ, then c1 ¼ c2. Therefore
½aꢀTD ðlabelledÞ ¼ aobsðLÞ=c1l1 ¼ ðaobsðUÞ ꢃ RMMU=RMMLÞ=c2l2 ¼ ½aꢀTD ðunlabelledÞ ꢃ ðRMMU=RMMLÞ.
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SPECIFIC ROTATION OF DEUTERIUM-CONTAINING ISOTOPOMERS
157
Table 1.
Ammonium salt
½aꢀ2D4
3
ꢂ42.8 (c 1.5, CHCl3)
ꢂ41.4 (c 1.5, CHCl3)
ꢂ35.7 (c 1.5, CHCl3)
ꢂ35.5 (c 1.5, CHCl3)
ꢂ26.6 (c 1.2, CHCl3)
3-d3
3-d6
3-d9
3-d15
isotopomer had a similar magnitude of rotation (of the plane) of plane-
polarized light. However, closer inspection} revealed that each isotopomer
intrinsically rotated (the plane of) plane-polarized light differently than its
non-isotopomeric counterpart (R)-3 due to their larger than expected
differences in specific rotations. This presumably is due to the subtle
differences between the deuterium atom (within a C–D bond) and the
hydrogen atom (within a C–H bond), and the resulting properties these
intrinsically play on their ability to rotate (the plane of) plane-polarized light.
Increasing the relative abundance of deuterium labels present with a particular
isotopomer could potential magnify this effect.1b,4 However, due to the limited
number of reported studies within this area and their conflicting outcomes, it is
difficult to conclude to what degree this effect influences the specific rotation.
In conclusion, we report a novel and efficient procedure for the synthesis of
isotopomeric pentamethyl ammonium salts (R,R)-3-d3, (R,R)-3-d6, (R,R)-3-d9
and (R,R)-3-d15, derived from 1,2-diaminocyclohexane (R,R)-1, and have
shown that these differential isotopomers rotate (the plane of) plane-polarized
light differently. This perhaps is due to a number of factors;
(a) the concentration effect (g/ml) and;
(b) differential enantiomers rotate (the plane of) plane-polarized light
differently.
Within our laboratory, we are currently exploring this phenomenon and these
studies will be reported in due course.
Experimental
All reactions were carried out under nitrogen using oven-dried glassware.
Proton and carbon NMR spectra were recorded on a Bruker AM 400 Fourier
transform spectrometer using an internal deuterium lock. Chemical shifts are
quoted in parts per million downfield from tetramethylsilane. Infrared spectra
were recorded on a Shimadzu 8300 FTIR machine. The levels of
D-incorporation were determined by a combination of mass and proton
NMR spectra. The specific rotations were measured on a Jasco P-1010
polarimeter between 24.1 and 24.88C. Each sample was subject to three
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G. S. COUMBARIDES ET AL.
separate optical rotations ðaobsÞ and the average of these three readings ðaaveÞ
were used to calculate the specific rotation. For consistency, the same
volumetric flask (2 ml) and analytical balance were used in each operation. For
mass spectrometry, samples were sent to the EPSRC national Mass Spectro-
metry Service Centre, Swansea.
(–)-N,N,N,N0,N0-2-Dimethylaminocyclohexyl-1-trimethylammonium iodide
(R,R)-3
Methyl iodide (0.24 g, 0.11 ml, 1.7 mmol) was added to a stirred solution of
(ꢂ)-N,N,N0,N0-tetramethyl-1,2-diaminocyclohexane (R,R)-4 (0.29 g, 1.7 mmol)
in dichloromethane (5 ml). The solution was stirred for 30 min. The solvent
was removed under reduced pressure to give (–)-N,N,N,N0,N0-2-dimethylami-
nocyclohexyl-1-trimethylammonium iodide (R,R)-3 (0.46 g, 87%) as a white
solid; RF [(chloroform/diethyl ether/acetone) 1:1:1] 0.10; ½aꢀ2D4 ¼ ꢂ48:8 (c 1.5,
CHCl3); mp 1268C; nmax(film)/cmꢂ1 3390, 2939 and 1454; dH(270 MHz,
CDCl3) 4.13 (1 H, td, J ¼ 11:0 and 3.7 Hz, NꢄCH), 3.44 (9 H, s, 3 ꢃ NꢄCH3),
2.68 (1 H, td, J ¼ 11:0 and 3.2 Hz, NCH), 2.37 (1 H, m, CH), 2.26 (6 H, s,
2 ꢃ NCH3), 1.97–1.72 (2 H, m, 2 ꢃ CH) and 1.62–1.15 (5 H, m, 5 ꢃ CH);
dC(100 MHz, CDC13) 71.8 (Nꢄ–C), 64.5 (NC), 53.8 (Nꢄ–CH3), 40.0
(N–CH3), 27.1, 24.9, 23.9 and 22.5 (4 ꢃ CH2) [found (M–I)+ 185.2010,
C11H25N2 requires M–I, 185.2018].
(–)-N,N,N,N0-2-Dimethylaminocyclohexyl-1-dimethyltrideuterioammonium
iodide (R,R)-3-d3
Methyl iodide-d3 (0.19 g, 0.08 ml, 1.3 mmol) was added to a stirred solution of
(–)-N,N,N0,N0-tetramethyl-1,2-diaminocyclohexane (R,R)-4 (0.22 g, 1.3 mmol)
in dichloromethane (5 ml). The solution was stirred for 30 min. The solvent
was removed under reduced pressure to give (–)-N,N,N,N0-2-dimethylamino-
cyclohexyl-1-dimethyltrideuterioammonium iodide (R,R)-3-d3 (0.38 g, 93%) as
a white solid; RF [(chloroform/diethyl ether/acetone) 1:1:1] 0.10; ½aꢀ2D4 ¼ ꢂ41:4
(c 1.5, CHCl3); mp 1268C; nmax(film)/cmꢂ1 3390, 2939, 2100 (CD) and 1454;
dH(270 MHz, CDCl3) 4.13 (1 H, td, J ¼ 11:0 and 3.7 Hz, Nꢄ–CH), 3.46 (6 H,
s, 2 ꢃ NꢄCH3), 2.68 (1 H, td, J ¼ 11:0 and 3.2 Hz, NCH), 2.37 (1 H, m, CH),
2.26 (6 H, s, 2 ꢃ NCH3), 1.97–1.72 (2 H, m, 2 ꢃ CH) and 1.62–1.15 (5 H, m,
5 ꢃ CH); dC(100 MHz, CDC13) 71.8 (NꢄC), 64.5 (NC), 53.8 (2 ꢃ NꢄCH3),
1
52.9 (1 C, septet, JC–D ꢅ20 Hz; NꢄCD3), 40.0 (NCH3), 27.1, 24.9, 23.9 and
22.5 (4 ꢃ CH2) [found (M–I)+ 188.2200, C11H12D3N2 requires M–I, 188.2201].
(–)-N,N0,N0-2-Methyltrideuterioaminocyclohexyl-1-dimethyltrideuterioammo-
nium iodide (R,R)-3-d6
Methyl iodide (0.30 g, 0.13 ml, 2.1 mmol) was added to a solution of (–)-N,N0-
dimethyl-d6-l,2-diaminocyclohexane (R,R)-9-d6 (0.12 g, 0.7 mmol) in dichlor-
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159
omethane (5 ml). The solution was stirred for 30 min. Lithium hydroxide
monohydrate (58 mg, 1.4 mmol) was added and stirring continued for another
hour. The mixture was decanted from inorganic solids and solvent was
removed to give (–)-N,N0,N0-2-methyltrideuterioaminocyclohexyl-1-dimethyl-
trideuterioammonium iodide (R,R)-3-d6 (0.24 g, 89%) as a white solid; RF
[(chloroform/diethyl ether/acetone) 1:1:1] 0.10; ½aꢀ2D4 ¼ ꢂ35:7 (c 1.5, CHCl3);
n
max(film)/cmꢂ1 3390, 2939 and 2100 (CD) and 1454; dH(270 MHz, CDCl3)
4.14 (1 H, td, J ¼ 11:0 and 3.7 Hz, NꢄCH), 3.43 (6 H, s, 2 ꢃ NꢄCH3), 2.68 (1
H, td, J ¼ 11:0 and 3.2 Hz, NCH), 2.39 (1 H, m, CH), 2.26 (3 H, s, NCH3),
2.04–1.76 (2 H, m, 2 ꢃ CH) and 1.58–1.17 (5 H, m, 5 ꢃ CH); dC(100 MHz,
CDC13) 72.1 (NꢄC), 64.9 (NC), 53.0 (2 ꢃ NꢄCH3), 52.9 (1 C, septet,
1JC–D ꢅ20 Hz; NꢄCD3), 40.1 (NCH3), 40.0 (1 C, septet, JC–D ꢅ20 Hz;
1
NCD3), 27.1, 24.9, 23.9 and 22.5 (4 ꢃ CH2) [found (M–I)+ 191.2389,
C11H19D6N2 requires M–I, 191.2389].
(–)-N,N0-2-Methyltrideuterioaminocyclohexyl-1-methylditrideuterioammonium
iodide (R,R)-3-d9
Methyl iodide-d3 (0.90 g, 0.40 ml, 6.3 mmol) was added to a stirred solution
of (–)-N,N0-dimethyl-l,2-diaminocyclohexane (R,R)-9 (0.30 g, 2.1 mmol) in
dichloromethane (5 ml). The solution was stirred for 30 min. Lithium
hydroxide monohydrate (0.15 g, 4.2 mmol) was added and stirring continued
for another hour. The mixture was decanted from inorganic solids and solvent
was removed to give (–)-N,N0-2-methyltrideuterioaminocyclohexyl-1-methyl-
ditrideuterioammonium iodide (R,R)-3-d9 (0.61 g, 92%) as a white solid; RF
[(chloroform/diethyl ether/acetone) 1:1:1] 0.10; ½aꢀ2D4 ¼ ꢂ35:5 (c 1.5, CHCl3);
n
max(film)/cmꢂ1 3390, 2939 and 2100 (CD) and 1454; dH(270 MHz, CDCl3)
4.11 (1 H, td, J ¼ 11:0 and 3.7 Hz, NꢄCH), 3.43 (3 H, s, NꢄCH3), 2.67 (1 H,
td, J ¼ 11:0 and 3.2 Hz, NCH), 2.38 (1 H, m, CH), 2.26 (3 H, s, NCH3),
1.96–1.76 (2 H, m, 2 ꢃ CH) and 1.58–1.17 (5 H, m, 5 ꢃ CH); dC(100 MHz,
CDC13) 72.0 (NꢄC), 64.9 (NC), 52.8 (NꢄCH3), 52.5 (2 C, br septet, JC–D
1
ꢅ20 Hz; 2 ꢃ NꢄCD3), 40.2 (NCH3), 40.1 (1 C, septet, 1JC–D ꢅ20 Hz; NCD3),
27.1, 24.9, 23.9 and 22.5 (4 ꢃ CH2) [found (M–I)+ 194.2578, C11H16D9N2
requires M–I, 194.2577].
(–)-N,N,N0,N0,N0-2-Ditrideuterioaminocyclohexyl-1-tri(trideuterio)ammonium
iodide (R,R)-3-d15
Methyl iodide-d3 (1.05 g, 0.47 ml, 7.5 mmol) was added to a stirred solution of
(–)-l,2-diaminocyclohexane (R,R)-1 (0.17 g, 1.5 mmol) in dichloromethane
(5 ml). The solution was stirred for 30 min. Lithium hydroxide monohydrate
(0.30 g, 7.5 mmol) was added sequentially over 2 h. The mixture was then
decanted from inorganic solids and solvent was removed to give
(–)-N,N,N0,N0,N0-ditrideuterioaminocyclohexyl-l-tri(trideuterio)ammonium
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iodide (R,R)-3-d15 (0.46 g, 99%) as a white solid; RF [(chloroform/diethyl
ether/acetone) 1:1:1] 0.10; ½aꢀ2D4 ¼ ꢂ26:6 (c 1.2, CHCl3); nmax(film)/cmꢂ1 2048
(C–D); dH(270 MHz, CDCl3) 4.08 (1 H, td, J ¼ 11:0 and 3.7 Hz, NꢄCH), 2.67
(1 H, td, J ¼ 11:0 and 3.2 Hz, NCH), 2.35 (1 H, m, CH), 1.96–1.79 (2 H, m,
2 ꢃ CH) and 1.58–1.17 (5 H, m, 5 ꢃ CH); dC(100 MHz, CDC13) 72.0 (NꢄC),
1
64.8 (NC), 52.5 (3 C, br septet, JC–D ꢅ20 Hz; 3 ꢃ NꢄCD3), 40.1 (3 C,
1
br septet, JC–D ꢅ20 Hz; 2 ꢃ NCD3), 27.1, 24.9, 23.9 and 22.5 (4 ꢃ CH2)
[found (M–I)+ 200.2951, C11H10D15N2 requires M–I, 200.2954].
Acknowledgements
We thank Queen Mary, University of London and GOSS Scientific
Instruments Ltd for their generous financial assistance, and Dr Ewan Boyd
(Syngenta, Grangemouth, Scotland) for his interest in this project.
References
1. (a) Alexander ER. J Am Chem Soc 1950; 72: 3796; (b) Paquette LA, Doecke CW,
Kearney FR, Drake AF, Mason SF. J Am Chem Soc 1980; 102: 7228;
(c) Polavarapu PL, Nafie LA, Benner SA, Morton TM. J Am Chem Soc 1981; 103:
5349; (d) Helmkamp GK, Joel CD, Sharman H. J Am Chem Soc 1956; 21: 844;
(e) Metzenthin T, Schreiber A, McMullan RK, Koetzle TF, Mosher HS, Bau R.
J Org Chem 1997; 62: 5017; (f) Guthrie RD. J Am Chem Soc 1967; 89: 6718;
(g) Streitwieser A. J Am Chem Soc 1953; 75: 5014.
2. Gottarelli G, Samori B. J Am Chem Soc 1981; 103: 471.
3. Yan S-J, McKinnie G, Abacherli C, Hill RK, Babior BM. J Am Chem Soc 1984;
106: 2961.
4. (a) Green MM, Andreola C, Munoz B, Reidy MP. J Am Chem Soc 1998;
110: 4063; (b) Forsyth DA, Johnson SM. J Am Chem Soc 1993; 115: 3364; (c)
Lifson S, Andreola C, Peterson NC, Green MM. J Am Chem Soc 1989; 111: 8850.
5. Djerassi C, Tursch B. J Am Chem Soc 1961; 83: 4609.
6. Lee S-F, Barth G, Kieslich K, Djerassi C. J Am Chem Soc 1978; 100: 3965.
7. Streitwieser A, Verbit L, Andreades S. J Org Chem 1965; 30: 2078.
8. Foltz EW, Lippman AE, Djerassi C. J Am Chem Soc 1965; 77: 4359; (b) Lyle GG.
J Org Chem 1960; 25: 1779.
9. Meyer WL, Lobo AP. J Am Chem Soc 1966; 88: 3181.
10. (a) Fletcher MD, Harding JR, Hughes RA, Kelly NM, Schmalz H, Sutherland A,
Willis CL. J Chem Soc, Perkin Trans 1 2000; 43; (b) Yan S-J, McKinnie G,
Abacherli C, Hill RK, Babior BM. J Am Chem Soc 1984; 106: 2961.
11. (a) Harding JR, Hughes RA, Kelly NM, Sutherland A, Willis CL. J Chem Soc,
Perkin Trans 1 2000; 3406; (b) Baldwin JE, Adlington RM, Crouch NP, Mellor
LC, Morgan N, Smith AM, Sutherland JD. Tetrahedron 1995; 51: 4089.
12. Verbit L. J Am Chem Soc 1967; 89: 167.
13. (a) Abbate S, Havel HA, Laux L, Pultz V, Moscowitz A. J Phys Chem 1998;
92: 3302; (b) Diem M, Polavarapu PL, Oboodi M, Nafie LA. J Am Chem Soc
1982; 104: 3329; (c) Lal BB, Diem M, Polavarapu PL, Oboodi M, Freedman TB,
Copyright # 2005 John Wiley & Sons, Ltd.
J Label Compd Radiopharm 2006; 49: 153–161

SPECIFIC ROTATION OF DEUTERIUM-CONTAINING ISOTOPOMERS
161
Nafie LA. J Am Chem Soc 1982; 104: 3336; (d) Freedman TB, Diem M,
Polavarapu PL, Nafie LA. J Am Chem Soc 1982; 104: 3343; (e) Freedman TB,
Kallmerten, Lipp ED, Young DA, Nafie LA. J Am Chem Soc 1988; 110: 689; (f)
Cianciosi SJ, Ragunathan N, Nafie LA, Lewis DK, Glenar DA, Baldwin JE.
J Am Chem Soc 1991; 113: 1865.
14. (a) Brewster JH. J Am Chem Soc 1959; 81: 5475; (b) Brewster JH. J Am Chem Soc
1959; 81: 5493; (c) Rosenfeld Z. Phys 1928; 52: 161.
15. Coumbarides GS, Boyd E, Eames J, Jones RVH, Stenson R, Suggate MJ.
Tetrahedron Lett 2005; 46: 1921.
16. Coumbarides GS, Boyd E, Eames J, Jones RVH, Motevalli M, Stenson R,
Suggate MJ. Tetrahedron Lett 2005; 46: 3473.
17. Coumbarides GS, Boyd E, Eames J, Jones RVH, Stenson R, Suggate MJ.
Tetrahedron Lett 2005; 46: 3479.
18. Suggate MJ. PhD Thesis, University of London, 2005.
19. Alexakis A, Chauvin A-S, Stouvenel R, Vrancken E, Mutti S, Mangeney P.
Tetrahedron: Asymmetry 2001; 12: 1171; (b) Kizirian J-C, Caille J-C, Alexakis A.
Tetrahedron Lett 2003; 44: 8893; (c) Mimoun H, de Saint Laumer JY, Giannini L,
Scopellita R, Floriani C. J Am Chem Soc 1999; 121: 6158; (d) Corey EJ, Sarshar S,
Azimioara MD, Newbold RC, Noe MC. J Am Chem Soc 1996; 118: 7851;
(e) Vasse J-L, Stranne R, Zalubovskis R, Gayet C, Moberg C. J Org Chem 2003;
68: 3258.
Copyright # 2005 John Wiley & Sons, Ltd.
J Label Compd Radiopharm 2006; 49: 153–161