Simple methodology for heck arylation at C-8 of adenine nucleosides

Article abstract of DOI:10.1002/adsc.200700418

A simple method for the arylation of 8-vinyladenine nucleoside derivatives is reported. With a broad set of aryl iodides and bromides, the reaction is catalyzed by the simple combination palladium acetate/tris(o-tolyl)phosphine/ triethylamine [Pd-(OAc)₂/(o-tol)₃P/Et₃N]. As expected, aryl chlorides are more difficult coupling partners but some undergo reactions with more exotic catalysts. Although trans-olefins are the major products, minor amounts of cis-isomers are detected in some cases, and a post-arylation mechanism for their formation is proposed. Finally, by subtle catalyst modulation chemoselective N-arylation of the nucleoside can be achieved in the presence of the vinyl moiety.

Full text of DOI:10.1002/adsc.200700418

FULL PAPERS
DOI: 10.1002/adsc.200700418
Simple Methodology for HeckArylation at C-8 of Adenine
Nucleosides
Pallavi Lagisetty,a Li Zhang,b and Mahesh K. Lakshmana,*
a
Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, New
York 10031, U.S.A.
Fax : (+1)-212 650-6107; e-mail: lakshman@sci.ccny.cuny.edu
Mass Spectrometry Facilities, Department of Chemistry, The University of Oklahoma, Norman, Oklahoma 73019, U.S.A.
b
Received: August 25, 2007; Published online: February 18, 2008
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: A simple method for the arylation of 8-vi- of cis-isomers are detected in some cases, and a post-
nyladenine nucleoside derivatives is reported. With a arylation mechanism for their formation is proposed.
broad set of aryl iodides and bromides, the reaction Finally, by subtle catalyst modulation chemoselective
is catalyzed by the simple combination palladium N-arylation of the nucleoside can be achieved in the
acetate/tris
A
[Pd- presence of the vinyl moiety.
A
ACHTREUNG
are more difficult coupling partners but some under-
go reactions with more exotic catalysts. Although Keywords: Heck reaction; nucleosides; palladium;
trans-olefins are the major products, minor amounts phosphanes; vinyl group
Introduction
factors that can influence enzymatic recognition.[7,8]
On the basis of these considerations, we set out to ex-
The physiological and medicinal importance of nu- plore the Heck reaction at the C-8 position of adenine
cleosides and their analogues has long been known, nucleosides. In this communication we report reac-
and these have, over years, spurred the development tions of iodo-, bromo- as well as chloroaromatics with
of novel methods for their syntheses.[1,2] In this con- vinyl nucleosides, and an evaluation of catalytic sys-
text, palladium-mediated transformations play
a
tems. We also investigate a trans-cis isomerization of
prominent role in providing access to hitherto un- the Heck products and provide an initial test of our
known structural motifs.[3] In addition, reactivities of hypothesis that subtly different catalysts can offer the
complex molecules such as nucleosides may not nec- possibility for modification at different sites within a
essarily parallel those of simpler compounds and they nucleoside.
can often provide novel insights. For these reasons it
is important to understand the catalyzed reactions of
nucleosides.
To our knowledge, among the various C C bond
forming reactions of nucleosides the Heck arylation Halonucleosides 1–3 were our starting substrates for
Results and Discussion
À
has not received significant attention. Although Heck this investigation. Commercially available 8-bromo-
reactions at the C-5 position of pyrimidine nucleo-
C
Modification at C-8 could have important biological utilize Pd(PPh3)4 and tri-n-butylvinylstannane or tet-
H
consequences. For instance, substitution at this posi- ravinylstannane in DMF or NMP as solvent. Al-
tion can influence the syn-anti conformational equilib- though these reactions proceed as reported, we found
rium around the glycosidic bond or produce structural it more convenient to prepare 4 from 2 and 5 from 3,
602
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Simple Methodology for Heck Arylation at C-8 of Adenine Nucleosides
FULL PAPERS
via the use of Pd(PPh3)4 (10 mol%), tri-n-butylvinyl-
G
stannane (2 mol equivs.) in anhydrous THF
(Scheme 1). These reactions were typically complete
Scheme 1. C-8 halo- and vinylnucleosides as substrates for
the arylation.
Figure 1. Ligands and preformed catalysts tested for the ary-
lation reactions.
within 24 h and provided the 8-vinyl products in derivatives can be achieved when the purine serves as
>85% yields (see the Supporting Information for de- the vinyl entity and not as the aryl halide.
tails). The 8-halo- as well as the 8-vinyladenine nu-
With these initial results, we next investigated other
cleosides formed the set of substrates for initial inves- catalytic systems for purposes of comparing reactivity.
tigations into the arylation.
A careful selection of entities was made based upon
Initial reactions of the halonucleosides with styrene their reported utility with simpler systems. Cat1[12]
proved to be unsatisfactory (entries 1–3 in Table 1) (Figure 1) constituted an obvious choice since L1/Pd-
even with P
G
(OAc)2 proved effective in the initial studies. L2, an
other hand, 4 and 5 underwent smooth reactions with air-stable species, has been shown to provide excellent
iodobenzene within short reaction spans with 10 results in Heck reactions of a hindered aryl chloride
mol% Pd
N
N
Et3N. The use of L1 in combination with iodobenzene shown to be effective in the activation of aryl chlor-
did not seem problematic,[11] and N-arylation was not ides for Heck reactions with a range of olefins.[14] L4
detected under these conditions. These results indi- has been shown to effectuate oxidative addition of
cate that effective Heck arylation of purines and their chlorobenzene, and Heck reactions with it produce
Table 1. Initial results on the Heck reactions leading to the C-8 modified adenine nucleosides.
Entry Substrate
Conditions[a]
Result[b]
1
2
1: X=Br, R=OTBDMS
10 mol% Pd
styrene
10 mol% Pd
quivs. styrene
10 mol% Pd
10 mol% Pd
C
11% yield in
24 h
3: X=I, R=H
G
Reduction of
3[c]
NR in 4 h
NR in 24 h
[d]
3
4
3: X=I, R=H
4: X=-CH=CH2,
R=OTBDMS
4: X=-CH=CH2,
R=OTBDMS
5: X=-CH=CH2, R=H
[d]
5
6
10 mol% Pd
(o-tol)3, 5 mol equivs. Et3N , 2 mol e-
3 h, 90%[e]
2 h, 92%[e]
quivs. iodobenzene
10 mol% Pd(OAc)2, 20 mol% P
quivs. iodobenzene
A
[a]
[b]
[c]
[d]
[e]
Reactions were conducted in DMF at 1008C.
Reactions were monitored by TLC.
Determined by the appearance of the H-8 resonance of adenosine in the H NMR of the crude product mixture.
No reaction observed.
1
Isolated yield of purified product.
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Pallavi Lagisetty et al.
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largely trans-arylated products,[15] and Cat2 has been ments have not provided insight into the observed dif-
utilized for Heck reactions of aryl chlorides.[16]
ferences in reactivity, it may be possible that the addi-
Table 2 is a listing of the most relevant results from tional equivalent of L1 is not simply a bystander (see
this series of experiments. With iodobenzene, forma- below). With Cat1 formation of the cis-product was
1
tion of the catalytic species from L1/Pd
A
proved to be superior to the use of Cat1 (entries 1 ture (explained later). Catalysts involving L2 and L3
and 2 in Table 2). Although 31P{1H} NMR experi- were useful but inferior. Other aryl iodides such as 1-
Table 2. Detailed evaluation of the arylation conditions and generality of the arylation of nucleoside substrates 4 and 5.
Entry
Aryl halide
Substrate
Conditions[a]
Result[b,c]
1
2
3
4
5
4
4
4
4
5
A
B
C
D
A
6a: 3 h, 90%
6a: 3 h, 70%[d]
6a: 8 h, 68%
6a: 24 h, 61%
7a: 2 h, 92%
6
7
8
9
4
4
4
4
4
A
B
E
D
F
6a: 4 h, 67%
6a: 6 h, 60%[d]
6a: 6 h, 62%[d]
6a: 24 h, 66%
6a: 24 h, 48%
10
11
4
A
6b: 2 h, 86%
12
13
4
5
A
A
6b: 2 h, 81%
7b: 2 h, 80%
14
15
4
5
A
A
6c: 7 h, 80%
7c: 2 h, 87%
16
17
4
5
A
A
6d: 5 h, 78%
7d: 2 h, 81%
18
5
A
7e: 2 h, 79%
19
20
4
5
A
A
6e: 4 h, 71%
7e: 5 h, 67%
21
22
23
4
5
5
A
A
G
6f: 5 h, 57%
7f: 5 h, 61%
7f: 24 h, 59%
24
25
4
5
A
A
6g: 24 h, 87%[d]
7g: 6 h, 82%[d]
26
27
4
5
A
A
6h: 5 h, 71%
7h: 5 h, 73%
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Simple Methodology for Heck Arylation at C-8 of Adenine Nucleosides
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Table 2. (Continued)
Entry
Aryl halide
Substrate
Conditions[a]
Result[b,c]
28
29
4
5
A
A
6i: 24 h, 86%[d]
7i: 24 h, 88%[d]
30
31
4
5
A
A
6j: 3 h, 89%
7j: 1 h, 91%
32
33
4
5
A
A
6k: 2 h, 81%
7k: 1 h, 96%
34
35
4
5
A
A
6l: 5 h, 82%
7l: 4 h, 91%
36
37
4
5
A
A
6m: 5 h, 79%
7m: 4 h, 89%
38
39
4
5
A
A
6n: 24 h, 89%
7n: 24 h, 91%
[a]
Conditions A: 10 mol% Pd
DMF, 1008C; C: 30 mol% PdCl2, 90 mol% L3, 1 mol equiv Cs2CO3, DMF, 1308C; D: 10 mol% Pd2
mol equivs. Cs2CO3, 1,4-dioxane, 908C; E: 10 mol% Cat1, 10 mol% L1, 5 mol equivs. Et3N, DMF, 1008C; F: 10 mol%
Pd(OAc)2, 20 mol% L4, 2 mol equivs. NaOAc, DMF, 1308C; G: 10 mol% Pd(OAc)2, 10 mol% L1, 5 mol equivs. Et3N,
ACHTREUNG
AHCTREUNG
A
ACHTREUNG
DMF, 1008C.
Reactions were monitored by TLC.
Isolated yield of purified product.
[b]
[c]
[d]
1
cis-Isomer was detected by H NMR.
iodonaphthalene, 4-iodo-1-nitrobenzene and 4-iodoto- tably, deactivated aryl bromides, 6-bromo-2-methoxy-
luene also underwent efficient reaction with 20 mol% naphthalene (entries 24 and 25), 4-bromoanisole (en-
L1/10 mol% Pd
1008C (Conditions A).
A
tries 26 and 27) and 4-bromo-N,N-dimethylaniline
(entries 28 and 29), all underwent reaction.
In order to broaden the scope of the reaction, aryl
At the initial stages of the investigation, the cis-
bromides were tested, and reactions were conducted alkene isomer was evident in the 1H NMR of the
with both the riboside 4 as well as the 2’-deoxyribo- crude product mixtures.[17] Subsequently, we discov-
side 5. These results are also displayed in Table 2. ered that the cis-isomer could form by a number of
With bromobenzene yields were lower than with io- ways. For example, in reactions of 4-bromotoluene
dobenzene (entries 6 and 7). Again, the in situ formed and 4-bromoanisole although only trans-olefins were
catalyst complex from L1 and Pd(OAc)2 was superior detected at the end of the reactions, we found that
U
to Cat1. In order to assess the influence of L1 on the the products were prone to isomerization on silica
course of the reaction, a coupling was performed with gel. However, in the cases of 6-bromo-2-methoxy-
10 mol% Cat1 and an additional 10 mol% L1. The naphthalene and 4-bromo-N,N-dimethylaniline the
result of this reaction was essentially identical to that cis-olefin isomers were evident in the crude reaction
obtained with Cat1 alone (entry 8). On the other mixtures. Therefore, 6n, a product that could undergo
hand, the additional equivalent of L1 seems necessary facile isomerization, was selected for further investi-
when used in combination with Pd
ple, as seen from entry 23, equimolar amounts of L1 isomer, exposure to CDCl3, silica gel and CH2Cl2 or
and Pd(OAc)2 (10 mol% each) led to a substantially acetone, all led to various levels of isomerization (see
slower reaction compared to entry 22 where 20 mol% the Supporting Information). Thus, it became clear
of L1 and 10 mol% of Pd(OAc)2 were employed. that a variety of factors could influence the trans-cis
The method is general and the simple combination isomerism ranging from photochemical to presence of
of L1/Pd(OAc)2 is of broad utility for reactions of the mildly acidic agents. The isomerization was pro-
vinylnucleosides with aryl iodides and bromides. No- nounced when electron-donating groups were present
A
ACHTREUNG
AHCTREUNG
ACHTREUNG
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Pallavi Lagisetty et al.
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tected. Nevertheless, in every case the trans olefin
was either the exclusive or the major product. When
possible, isomerization could be avoided through the
use of neutral alumina for chromatography as well as
eliminating contact of the product with CHCl3 and
CH2Cl2. In some cases, chromatography on silica gel
was unavoidable and in these cases rapid purification
was necessary.
Scheme 2. A possible mechanism for the trans-cis isomeriza-
tion of some arylation products.
We next focused on the activation of aryl chlorides
for the transformation (Table 3). L2, L3, L4 and Cat2
had been selected due to their ability to activate aryl
Table 3. Use of aryl chlorides for the arylation.
Entry Aryl chlo-
ride
Substrate Conditions[a] Result[b,c]
À
C Cl bonds. Aryl chlorides containing electron-with-
drawing groups could be effectively utilized, with
Cat2 providing the better conversions (entries 4 and
6). As expected the reaction of 4-chloroanisole was
inefficient.
6a: 48 h,
65%
6a: 5 h, 52%
6c: 24 h,
59%
1
2
3
4
4
4
4
4
C
F
Pd catalysis has proven to be incredibly powerful
[18]
F
À
for C Nbond forming reactions,
and this has also
provided access to a variety of N-arylated nucleoside
analogues.[3a] Therefore, we tested the hypothesis that
catalysts with differing reactivities can be utilized for
functionalization at different reactive centers of nu-
H
6c: 3 h, 64%
5
6
4
4
F
H
6j: 24 h, 57%
6j: 4 h, 67%
cleosides. Using our recently reported method,[19]
4
[a]
Conditions C: 30 mol% PdCl2, 90 mol% L3, 1 mol equiv
could be N-arylated in 69% yield (Scheme 3) without
vinyl arylation. This unoptimized reaction provided
clear evidence that catalyst modulation can be utilized
for chemoselective functionalization at different sites
within the same molecule.
˚
Cs2CO3, DMF, 130 C; F: 10 mol% Pd(OAc)2, 20 mol%
G
L4, 2 mol equivs. NaOAc, DMF, 1308C; H: 10 mol%
Cat2, 1 mol equiv NaOAc, 6 mol equivs. (n-Bu)4N+BrÀ,
DMA, 1508C.
Reactions were monitored by TLC.
Isolated yield of purified product.
[b]
[c]
on the aryl moieties, as in the cases of 6-bromo-2-me- Conclusions
thoxynaphthalene as well as 4-bromo-N,N-dimethyl-
ACHTREUNG
As shown in Scheme 2, any weak electron-acceptor drawing group leading to selective functionalization
including the metal itself could, through coordination at the b-C of the olefin. Aryl iodides and a wide
with the N7, lead to a benzylic cation. Such a species range of the more common aryl bromides can be ef-
would be stabilized by electron-donor groups on the fectively utilized for these reactions. The combination
aromatic moiety. Consistent with this notion, product (o-tol)3P (L1)/Pd(OAc)2/Et3N(2:1 ligand/Pd stoichi-
G
6e from 4-bromotoluene isomerized upon contact ometry) proved to be effective and was superior in re-
with silica gel, but the isomeric 6f did not to any ob- activity to the well-defined Cat1. The role of addition-
servable extent. In the case of 6f, it is plausible that al L1 is currently unclear but the one example in
coplanarity necessary for the isomerization is ob- Table 2 where equimolar amounts (10 mol% each) of
structed by the presence of the o-methyl group. Simi- L1 and Pd(OAc)2 were used (entry 23) demonstrates
G
larly, when electron-withdrawing substituents were that the additional equivalent of L1 is necessary, the
present on the aryl moiety, no isomerization was de- absence of which led to retardation of the reaction.
Scheme 3. N6-Arylation of the C-8 vinylnucleoside by catalyst modulation.
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Simple Methodology for Heck Arylation at C-8 of Adenine Nucleosides
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the proportions of reagents and solvents were appropriately
adjusted. Reactions were monitored by TLC and upon con-
sumption of the starting material, the reaction mixtures
were diluted with EtOAc (10 mL) and washed with brine
(5 mL) and then twice with water. The organic layer was
separated, dried (Na2SO4) and concentrated. The crude re-
action products were purified by column chromatography
using appropriate solvents (listed under the individual com-
pound headings in the Supporting Information). Fractions
containing pure product were combined, evaporated and
dried under vacuum.
Although trans-alkenes are the predominant products,
in some cases isomerization to the cis-alkene can
occur after the arylation. This may be the reason for
the minor trans-olefins observed in the catalytic re-
duction of C-8 alkynyl-2’-deoxyadenosine.[10b] The
methodology described here should be applicable to
many related heteroaryl compounds and the proposed
olefin isomerization mechanism may occur in a varie-
ty of other systems that contain basic nitrogen atoms.
Aryl chlorides can also be used for the chemistry de-
scribed, although at the present time efficient conver-
sions were observed only with activated aromatic
compounds. As shown with the one preliminary ex-
ample in Scheme 3 it appears that reactivity of the
With aryl bromides (Conditions A): A mixture of Pd-
A
N
(31 mL, 0.22 mmol), 8-vinylnucleoside 4 (30 mg, 0.047 mmol)
and aryl bromide (2 mol equivs.) in DMF (0.5 mL) was pre-
pared in an oven-dried vial, equipped with a stirring bar.
The reaction mixture was flushed with N2 gas, sealed with a
Teflon lined cap, and placed in a sand bath that was main-
tained at 100–1058C. Although the general procedure de-
scribed is for reactions on the 30 mg scale of 4, some reac-
tions were conducted at different scales and in these cases
the proportions of reagents and solvents were appropriately
adjusted. Reactions were monitored by TLC and upon con-
sumption of the starting material, the reaction mixtures
were diluted with EtOAc (10 mL) and washed with brine
(5 mL) and then twice with water. The organic layer was
separated, dried (Na2SO4) and concentrated. The crude re-
action products were purified by column chromatography
using appropriate solvents (listed under the individual com-
pound headings in the Supporting Information). Fractions
containing pure product were combined, evaporated and
dried under vacuum.
À
catalyst can be modulated, leading to C Nreactions
in the presence of the vinyl moiety. Finally, in compar-
ison to the single reported Suzuki–Miyaura reaction
at the C-8 position using trans-b-styreneboronic
acid,[20] the present method is superior in terms of
product yield, and is of wider scope since it does not
depend on the availability of the rare trans-b-styrene-
boronic acid derivatives.
Experimental Section
Thin layer chromatography was performed on 250 mm silica
plates and column chromatographic purifications were per-
formed on 200–300 mesh silica gel and neutral alumina as
needed. Solvents used for eluting the compounds, as well as
TLC conditions and Rf values are provided under individual
compound headings (see the Supporting Information). THF
was distilled over LiAlH4 and redistilled over sodium and
With aryl chlorides (Conditions F): Within a N2 gas-filled
glove bag, a mixture of Pd(OAc)2 (1.7 mg, 7.6 mmol), diiso-
G
propylphospinobutane (4.5 mL, 15.5 mmol), NaOAc (13.0 mg,
0.16 mmol), 8-vinylnucleoside 4 (50 mg, 0.08 mmol) and aryl
chloride (2 mol equivs.) in DMF (0.8 mL) was prepared in
an oven-dried vial, equipped with a stirring bar. The reac-
tion mixture was sealed with a Teflon lined cap, removed
from the glove bag and placed in a sand bath that was main-
tained at 130–1358C. Reactions were monitored by TLC
and upon consumption of the starting material, the reaction
mixtures were diluted with EtOAc (10 mL) and washed with
brine (5 mL) and then twice with water. The organic layer
was separated, dried (Na2SO4) and concentrated. The crude
reaction products were purified by column chromatography
using appropriate solvents (listed under the individual com-
pound headings in the Supporting Information). Fractions
containing pure product were combined, evaporated and
dried under vacuum.
Et3Nwas distilled over CaH . All other reagents as well as
2
anhydrous DMF were obtained from commercial sources
1
and used without further purification. H NMR spectra were
recorded at 500 MHz and were referenced to residual pro-
tonated solvent. 13C NMR spectra were recorded at
125 MHz and were referenced to the 13C signals of the sol-
vent. Chemical shifts (d) are reported in parts per million
(ppm) and coupling constants (J) are in hertz (Hz). The
sugar ring is numbered 1’-5’ beginning at the anomeric
carbon and proceeding via the carbon chain to the primary
carbinol carbon. The conventional numbering is used for the
purine. Complete characterization data for all compounds is
available in the Supporting Information.
Typical Procedure for the Arylation of 8-Ethenyl-
With aryl chlorides (Conditions H): A mixture of Cat2
(8.9 mg, 8 mmol), NaOAc (7.7 mg, 0.09 mmol), (nBu)4N+BrÀ
(160 mg, 0.48 mmol), 8-vinylnucleoside 4 (50 mg, 0.08 mmol)
and aryl chloride (2 mol equivs.) in N,N-dimethylacetamide
(0.8 mL) was prepared in an oven-dried vial, equipped with
a stirring bar. The reaction mixture was flushed with N2 gas,
sealed with a Teflon lined cap, and placed in a sand bath
that was maintained at 150–1558C. Reactions were moni-
tored by TLC and upon consumption of the starting materi-
al, the reaction mixtures were diluted with EtOAc (10 mL)
and washed with brine (5 mL) and then twice with water.
The organic layer was separated, dried (Na2SO4) and con-
2’,3’,5’-tris-O-(tert-butyldimethylsilyl)adenosine (4)
With aryl iodides (Conditions A): A mixture of Pd
A
(1.7 mg, 7.6 mmol), P(o-tol)3 (4.7 mg, 15.4 mmol), Et3N
AHCTREUNG
(55 mL, 0.39 mmol), 8-vinylnucleoside 4 (50 mg, 0.08 mmol)
and aryl iodide (2 mol equivs.) in DMF (0.8 mL) was pre-
pared in an oven-dried vial, equipped with a stirring bar.
The reaction mixture was flushed with N2 gas, sealed with a
Teflon lined cap, and placed in a sand bath that was main-
tained at 100–1058C. Although the general procedure de-
scribed is for reactions on the 50 mg scale of 4, some reac-
tions were conducted at different scales and in these cases
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Pallavi Lagisetty et al.
FULL PAPERS
centrated. The crude reaction products were purified by
column chromatography using appropriate solvents (listed
under the individual compound headings in the Supporting
Information). Fractions containing pure product were com-
bined, evaporated and dried under vacuum.
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[3] For reviews, see: a) M. K. Lakshman, Curr. Org. Synth.
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Bergstrom, M. K. Ogawa, J. Am. Chem. Soc. 1978, 100,
8106–8112.
Typical Procedure for the Arylation of 8-Ethenyl-
3’,5’-bis-O-(tert-butyldimethylsilyl)-2’-deoxyadenosine
(5)
With aryl iodides and bromides (Conditions A): A mixture
of Pd
N
N
[5] A. Bråthe, L.-L. Gundersen, F. Rise, A. B. Eriksen,
A. V. Vollsnes, L. Wang, Tetrahedron 1999, 55, 211–
228.
mmol), Et3N(68 mL, 0.49 mmol), 8-vinylnucleoside 5 (50 mg,
0.10 mmol) and aryl iodide or aryl bromide (2 mol equivs.)
in DMF (1.0 mL) was prepared in an oven-dried vial,
equipped with a stirring bar. The reaction mixture was flush-
ed with N2 gas, sealed with a Teflon lined cap, and placed in
a sand bath that was maintained at 100–1058C. Reactions
were monitored by TLC and upon consumption of the start-
ing material, the reaction mixtures were diluted with EtOAc
(10 mL) and washed with brine (5 mL) and then twice with
water. The organic layer was separated, dried (Na2SO4) and
concentrated. The crude reaction products were purified by
column chromatography using appropriate solvents (listed
under the individual compound headings in the Supporting
Information). Fractions containing pure product were com-
bined, evaporated and dried under vacuum.
ˇ
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Supporting Information
Analysis of methods for the synthesis of 4 and 5, details of
their synthesis and characterization, complete characteriza-
tion data for 6a–n and 7a–n, synthesis and characterization
1
of 8. H N MR of6n showing the trans to cis isomerization.
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Acknowledgements
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ganometallics 1992, 11, 1995–1996.
This work was supported by NSF Grant CHE-0640417, a
PSC-CUNY 38 award and partially by NIH Grant S06
GM008168–24S1. Acquisition of a mass spectrometer was
funded by NSF Grant CHE-0520963 (M.K.L). Dr. Chris
Woltermann (FMC Corporation) is thanked for a generous
gift of several of the alkyl phosphine tetrafluoroborate salts.
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[17] The predominant trans-olefin isomers had a Jtrans
=
15.3–16.6 Hz whereas in those cases where a cis-isomer
was observed the Jcis =12.2–12.8 Hz. The vinyl protons
of the trans-isomers were more downfield shifted than
those of the cis.
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