Chiral recognition in silver(I) olefin complexes with chiral diamines. Resolution of racemic alkenes and NMR discrimination of enantiomers

Article abstract of DOI:10.1021/om0341653

The fragment [(chiral diamine)Ag]⁺ is a very useful reagent, both for the resolution of racemic alkenes and for the ¹H or ¹³C NMR determination of the enantiomeric abundances of chiral olefinic compounds.

Full text of DOI:10.1021/om0341653

Organometallics 2004, 23, 15-17
15
Ch ir a l Recogn ition in Silver (I) Olefin Com p lexes w ith
Ch ir a l Dia m in es. Resolu tion of Ra cem ic Alk en es a n d
NMR Discr im in a tion of En a n tiom er s
Maria E. Cucciolito, Germana Flores, and Aldo Vitagliano*
Dipartimento di Chimica, Universita` di Napoli Federico II,
Complesso Universitario di Monte Sant’Angelo, via Cintia, 80126 Napoli, Italy
Received September 10, 2003
Summary: The fragment [(chiral diamine)Ag]+ is a very
Sch em e 1
useful reagent, both for the resolution of racemic alkenes
and for the 1H or 13C NMR determination of the
enantiomeric abundances of chiral olefinic compounds.
Chiral recognition in the coordination of olefins to
chiral transition-metal fragments is a topic of great
interest,1 not only because of its involvement in metal-
promoted enantioselective syntheses2 but also because
it can offer simple procedures for the thermodynamic3
or kinetic4 resolution of racemic mixtures or for the
analytical determination of relative enantiomeric abun-
dances.5
We recently reported a detailed investigation of
trigonal Cu(I) olefin complexes with the chiral diamine
N,N′-bis(mesitylmethyl)-1,2-diphenyl-1,2-ethanedi-
amine (1), which led to a fairly good understanding of
the factors affecting stereoselectivity in these species.6
One remarkable property of the [(S,S)-1-Cu]+ fragment
proved to be the ability to selectively coordinate the R
enantiomer of secondary allylic alcohols, providing a
simple and effective method for the resolution of these
compounds.3a,6 Following our studies on Cu(I) com-
plexes, we were prompted to prepare analogous Ag(I)
species, both to determine whether the larger size of the
metal ion could affect the stereochemical properties of
the complexes and to investigate whether its higher
lability and air stability could be exploited in practically
useful methods. Although silver-olefin adducts are
about the oldest metal π-complexes known,7 very few
studies on chiral species appear to have been reported
in the literature, and these are essentially limited to
the use of silver salts, in combination with chiral
lanthanide shift reagents, for the NMR discrimination
of enantiomeric olefins.5a,b In this communication we
report the use of the [(S,S)-1-Ag]+ and [(S,S)-2-Ag]+
adducts as effective reagents for the resolution of
racemic olefins (especially allylic alcohols) and for the
NMR determination of the enantiomeric excess of chiral
olefinic compounds.
Tricoordinate cationic complexes of general formula
[(N-N)Ag(olefin)]+ were rapidly formed by suspending
a silver salt (triflate, fluoroborate, or nitrate) in dichlo-
romethane (0.1 mmol/mL) at room temperature and
adding 1 equiv of the diamine and an excess (from 3 to
5 equiv) of the appropriate olefin (Scheme 1).
The nitrate salts are generally less soluble and best
suited to achieve an optimal resolution of chiral olefins.
They separated from the reaction mixture as a gelatin-
ous solid by addition of diethyl ether (in the case of
allylic alcohols) or pentane (in the case of hydrocarbon
olefins).8 The gel generally showed a poor to moderate
diastereomeric enrichment, but when the mixture was
stirred overnight, it was converted in better than 95%
yield (based on Ag) to a crystalline material which
contained the enantiomerically enriched olefin in up to
99% ee, the best resolutions being achieved in the case
of secondary allylic alcohols and diamine 1 (Table 1).9
* To whom correspondence should be addressed. E-mail: alvitagl@
unina.it.
(1) Gladysz, J . A.; Boone, B. J . Angew. Chem., Int. Ed. Engl. 1997,
36, 550-583.
(2) (a) Advances in Catalytic Processes; Doyle, M. P., Ed.; J AI
Press: London, 1997; Vol. 1. (b) Advances in Catalytic Processes; Doyle,
M. P., Ed.; J AI Press: London, 1997; Vol. 2.
(3) (a) Cucciolito, M. E.; Ruffo, F.; Vitagliano, A.; Funicello, M.
Tetrahedron Lett. 1994, 35, 169-170. (b) Paiaro, G. Organomet. Chem.
Rev. 1970, 6, 319-335 and references therein. (c) Goldman, M.;
Kustanovich, Z.; Weinstein, S.; Tishbee, A.; Gil-Av, E. J . Am. Chem.
Soc. 1982, 104, 1093.
(4) (a) Visser, M. S.; Heron, N. M.; Didiuk, M. T.; Sagal, J . F.;
Hoveyda, A. H. J . Am. Chem. Soc. 1996, 118, 4291-4298. (b) Visser,
M. S.; Harrity, J . P. A.; Hoveyda, A. H. J . Am. Chem. Soc. 1996, 118,
3779-3780. (c) Morken, J . P.; Didiuk, M. T.; Visser, M. S.; Hoveyda,
A. H. J . Am. Chem. Soc. 1994, 116, 3123-3124. Kitamura, M.;
Kasahara, I.; Manabe, K.; Noyori, R.; Takaya, H. J . Org. Chem. 1988,
53, 708-710.
(5) (a) Wenzel, T. J .; Sievers, R. E. J . Am. Chem. Soc. 1982, 104,
382-388. (b) J ohns, L.; Belt, S.; Lewis, C. A.; Rowland, S.; Masse´, G.;
Robert, J .-M.; Ko¨nig, W. A. Phytochemistry 2000, 53, 607-611. (c)
Uccello-Barretta, G.; Bernardini, R.; Balzano, F.; Caporusso, A. M.;
Salvadori, P. Org. Lett. 2001, 3, 205-207. (d) Uccello-Barretta, G.;
Bernardini, R.; Lazzaroni, R.; Salvadori, P. Org. Lett. 2000, 2, 1795-
1798.
(7) (a) Winstein, S.; Lucas, H. J . J . Am. Chem. Soc. 1938, 60, 836-
847. (b) Cope, A. C.; Estes, L. L. J . Am. Chem. Soc. 1950, 72, 1128-
1132.
(8) If diethyl ether is used to precipitate the complexes of hydro-
carbon olefins, partial or even total loss of the olefin may take place
by a displacement reaction.
(6) Cavallo, L.; Cucciolito, M. E.; De Martino, A.; Giordano, F.;
Orabona, I.; Vitagliano, A. Chem. Eur. J . 2000, 6, 1127-1139.
10.1021/om0341653 CCC: $27.50 © 2004 American Chemical Society
Publication on Web 12/05/2003

16 Organometallics, Vol. 23, No. 1, 2004
Communications
Ta ble 1. Resolu tion of Olefin s via
[(d ia m in e)Ag(olefin )]X Com p lexes. En a n tiom er ic
Excesses in th e P r ecip ita ted P r od u cta
with a lower solubility of the corresponding diastere-
omer in achieving the final good resolution.
With respect to the metal-olefin bond, the complexes
of hydrocarbon olefins appear to be very weak and
labile, while those with allylic alcohols are more stable
and robust, very likely because of a stabilizing intramo-
lecular interaction between the oxygen atom and the
metal ion.6,12 Accordingly, two different procedures were
adopted to recover the resolved alkene. In the case of
hydrocarbon olefins (procedure i), the complex was
dissolved in the minimum amount of dichloromethane
and ethylene was gently bubbled through the solution
while simultaneously adding pentane. This caused the
immediate and nearly quantitative precipitation of the
ethylene complex, while the resolved olefin could be
isolated by fractional distillation of the mother liquor.
This procedure has the advantage of leaving the [(N-
N)Ag]+ fragment intact and directly available to coor-
dinate a further batch of olefinic compound. In the case
of allylic alcohols (procedure ii), ethylene is not able to
displace the coordinated olefin, and therefore the solid
complex was treated with NaI (1.5 equiv) and aqueous
HCl (3 M) with vigorous stirring, and the resolved allylic
alcohol was recovered from the slurry in better than 95%
yield by extraction with pentane and successive frac-
tional distillation of the extract. The diamine was
recovered from the residual aqueous suspension by
addition of NaOH, extraction with dichloromethane, and
evaporation of the solvent (ca. 95% yield).11 Both
procedures i and ii are remarkably simple, involving few
steps and little workup, and are suitable to recycle the
same crop of chiral diamine to resolve successive batches
of olefinic compound.
diamine
X-
olefin
amt, equivb ee, %
-
(S,S)-1 NO3 CH2dCHCH(OH)Me
CH2dCHCH(OH)(CH2)4Me
3
3
4
5
5
5
5
5
5
5
5
5
93
85
94
>98
(E)-MeCHdCHCH(OH)Me
CH2dCHCH(Me)CMe3
CH2dCHCH(Me)CHMe2
>98
81c
41
39
67
25
85
60
CH2dCHCH(Me)CH2Me
-
(S,S)-1 BF4
CH2dCHCH(OH)Me
CH2dCHCH(Me)CMe3
-
(S,S)-2 NO3 CH2dCHCH(OH)Me
CH2dCHCH(Me)CMe3
a
In all the cases, chemical yields (based on silver) were close
to 95%. In the case of allylic alcohols, the R enantiomer was
b
obtained. Equivalents of racemic olefin used to prepare the
complex. c R enantiomer.
Although a detailed stereochemical investigation of
the complexes is out of the scope of the present com-
munication, we point out that they are very likely to be
isostructural with the previously investigated Cu(I)
adducts,6 since the same olefinic enantiomer (R in the
case of secondary allylic alcohols) is enriched upon
coordination. In our previous study concerning Cu(I)
complexes,6 the resolution of secondary allylic alcohols
could be ascribed to the preferential coordination of one
enantiomer with 95-98% selectivity. In the case of
silver complexes the selectivity appears to be substan-
tially lower, as indicated by the counterion dependence
of the ee’s and by the fact that the initially precipitated
amorphous solids did not display large enantiomeric
excesses of the olefin. Nevertheless, the final crystalline
solids (nitrate salts) showed in all the cases a better
diastereomeric purity than for the corresponding copper-
(I) derivatives.10 This indicates the concurrence of a
moderate preferential coordination of one enantiomer
The enantiomeric excess could be directly estimated
1
from the H NMR spectrum of the isolated crystalline
complex in CDCl3, CD2Cl2, or acetone-d6, since many
signals of the minor diastereomer are well separated
from those of the major one. The large differences in
the coordination shifts of the two enantiomers is most
likely due to the different shielding effects by the mesityl
rings of the diamine ligand. As shown in our previous
study on analogous Cu(I) species,6 in the most stable
conformation the mesityl rings protrude forward to
“envelop” the sides of the third coordinative position (as
schematically shown in Scheme 1), thus generating
shielding effects on the coordinated olefin which are very
sensitive to the spatial location of each proton. This
prompted us to explore the use of [(N-N)Ag]NO3 and
[(N-N)Ag]OTf salts as chiral shift reagents for the NMR
discrimination of enantiomeric olefins.13 Such reagents
would indeed be complementary or even advantageous
over those containing lanthanide ions,5a,b due to the lack
of line broadening caused by the paramagnetic ions. Of
(9) Selected data for representative complexes are as follows. [(S,S)-
1-Ag-(R)-1-bu ten -3-ol]NO3 (major diastereomer). Anal. Calcd for
38H48AgN3O4: C, 63.51; H, 6.73; N, 5.85. Found: C, 63.15; H, 6.95;
C
N, 5.64. 1H NMR (400 MHz, CD2Cl2): δ 0.93 (d, 3H, Me), 2.19 (s, 12H,
o-MeN-N), 2.21 (s, 6H, p-Me (N-N)), 3.32 (br, 1H, CHOH), 3.42-3.60
(m, 6H, CH2 (N-N) and NH), 3.72 (d, 1H, OH), 4.07 (d, 1H, dCH1Z),
4.26 (m, 2H, CH (N-N)), 4.54 (d, 1H, dCH1E), 5.31 (ddd, 1H, dCH2).
13C NMR (100.6 MHz, CD2Cl2): δ 19.9 (o-Me(N-N)), 21.0 (p-Me (N-
N)), 23.5 (Me), 46.8 (CH2 (N-N)), 66.9 (CHOH), 69.3 (CH (N-N)), 94.1
(br, dCH2), 135.5 (br, dCH). [(S,S)-1-Ag-(S)-1-bu ten -3-ol]NO3 (minor
diastereomer). 1H NMR (400 MHz, CD2Cl2): δ 1.06 (d, 3H, Me), 4.01
(br, 1H, CHOH), 4.60 (d, 1H, dCH1Z), 4.68 (d, 1H, dCH1E), 5.50 (ddd,
1H, dCH2). [(S,S)-1-Ag-(R)-1-octen -3-ol]NO3. Anal. Calcd for C42H56
-
AgN3O4: C, 65.11; H, 7.28; N, 5.42. Found: C, 65.37; H, 7.45; N, 5.32.
1H NMR (400 MHz, CD2Cl2): δ 0.90 (t, 3H, Me), 2.22 (br, 18H, Me
(N-N)), 3.13 (br, 1H, CHOH), 3.45-3.60 (m, 6H, CH2 (N-N) and NH),
3.92 (d, 1H, OH), 4.03 (d, 1H, dCH1Z), 4.35 (m, 2H, CH (N-N)), 4.47
(d, 1H, dCH1E), 5.20 (ddd, 1H, dCH2). 13C NMR (100.6 MHz, CD2Cl2):
δ 14.3 (Me), 20.0 (o-Me (N-N)), 21.0 (p-Me (N-N)), 23.2, 25.8, 32.5,
37.9 (4CH2), 46.9 (CH2 (N-N)), 69.4 (CH (N-N)), 70.7 (CHOH), 93.7
(br, dCH2), 134.1 (br, dCH). [(S,S)-1-Ag-(R)-3,4,4-Me3-1-p en ten e]-
NO3 (major diastereomer). Anal. Calcd for C42H56AgN3O3: C, 66.48;
H, 7.44; N, 5.54. Found: C, 66.17; H, 7.35; N, 5.62. 1H NMR (400 MHz,
CD2Cl2): δ 0.81 (s, 9H, 3Me), 0.82 (d, 3H, CHMe), 1.77 (dq, 1H, CHMe),
2.12 (s, 12H, o-Me (N-N)), 2.21 (s, 6H, p-Me (N-N)), 2.96 (br, 2H,
NH), 3.56 (m, 4H, CH2 (N-N)), 4.03 (m, 2H, CH (N-N)), 4.57 (dd, 1H,
dCH1E), 4.81 (dd, 1H, dCH1Z), 5.60 (ddd, 1H, dCH2). 13C NMR (100.6
MHz, CD2Cl2): δ 16.4 (CHMe), 19.8 (o-Me (N-N)), 21.0 (p-Me (N-
N)), 27.5 (3Me), 32.9 (CMe3), 46.7 (CH2 (N-N)), 48.6 (CHMe), 69.2 (CH
(N-N)), 107.5 (br, dCH2), 140.1 (br, dCH). [(S,S)-1-Ag-(S)-3,4,4-Me3-
1-p en ten e]NO3 (minor diastereomer). 1H NMR (400 MHz, CD2Cl2):
δ 0.80 (s, 9H, 3Me), 0.90 (d, 3H, CHMe), 4.82 (dd, 1H, dCH1E), 4.85
(dd, 1H, dCH1Z), 5.74 (ddd, 1H, dCH2).
(11) Silver can be easily and quantitatively recovered as pure metal
by reduction of the precipitated AgI with Zn powder in 0.1 M aqueous
HCl and successive removal of the excess Zn with 5 M aqueous HCl.
(12) It is known that olefinic alcohols can form chelate adducts with
silver ions; see: Novak, M.; Aikens, D. A.; Closson, W. D. Inorg. Nucl.
Chem. Lett. 1974, 10, 1117-1121. Moreover, on the sole basis of
inductive effects on the Ag-olefin bond, allylic alcohols would be
expected to give less stable adducts than, for example, ethylene, which
implicitly supports the existence of an O‚‚‚Ag stabilizing interaction
in their complexes. See: Herberhold, M. In Metal π-Complexes;
Elsevier: Amsterdam, London, New York, 1974; Vol. 2, part II, pp 150-
151. An additional stabilization could in principle arise from an
intramolecular N-H‚‚‚O bond, which, however, seems unlikely since
X-ray diffraction data show that such an H-bond is not present in the
analogous Cu(I) complexes.6
(10) It should be noted that in the case of the Cu(I) complexes, to
prevent oxidation, nitrate could not be used as a counterion.

Communications
Organometallics, Vol. 23, No. 1, 2004 17
the two diamines, (S,S)-1 appears to be better suited to
the purpose, both because the silver salts of (S,S)-2 have
1
a pronounced tendency to darken and because the H
NMR signals of (S,S)-2 obscure a wider spectral range.
An NMR sample suitable for the accurate determination
of enantiomeric abundances contained a 10-30 mM
solution of the [(N-N)Ag]X salt (X ) NO3, OTf) and 1-3
equiv of the olefin in CDCl3, CD2Cl2, or acetone-d6. In
either solvent the olefin is in fast exchange (on the NMR
time scale) on the silver ions and therefore gives signals
whose shifts are averaged between the free and coor-
dinated molecules. Since the chemical shifts of the olefin
in the diastereomeric complexes are generally different,
the [(N-N)Ag]+ fragment does indeed act as a chiral
shift reagent, and many of the NMR signals of the
olefin’s enantiomers present in the sample are well
separated (Figure 1).
In the presence of an excess of olefin, or other
potentially coordinating species, the magnitude of the
signal separation results from a balance of the different
coordination shifts of the two enantiomers and of their
binding affinities to the chiral metal fragment. Accord-
ingly, the solvent and the counterion may have a
substantial effect on the magnitude of the signal separ-
ation, depending on their coordinating ability. In the
case of the more weakly bound hydrocarbon olefins, the
signal separations generally increase in the counterion
order OTFA- < NO3 < OTf- and in the solvent order
-
acetone < CDCl3 (Table S1 in the Supporting Informa-
tion).14 Due to the dissociation and exchange equilibria,
the amount of signal inequivalence is of course affected
by the concentrations of the olefin and of the chiral
metal fragment. While the particular choice of the
concentrations is usually not crucial (thus adding flex-
ibility to the method), this dependence can be turned
into an advantage, because in the case of fortuitous
overlapping of important resonances, the addition of a
small amount of silver salt or olefin usually removes
the incidental degeneracy and results in a satisfactory
separation of the signals.
F igu r e 1. (a) Middle part of the 400 MHz 1H NMR
spectrum (CD2Cl2) of 1-buten-3-ol (enriched in R isomer).
(b) Middle part of the 100.6 MHz 13C NMR spectrum
(acetone-d6) of racemic 3-vinylcyclohexene. Lower traces
show the olefin alone and upper traces the olefin in the
presence of [(S,S)-1-Ag]OTf. Concentrations: (a) 13 mM
complex, 40 mM olefin; (b) 35 mM complex, 40 mM olefin.
In conclusion, (chiral diamine)-Ag+ salts, in addition
to being useful resolving agents, appear to provide a
simple method for the NMR determination of the
enantiomeric abundances of a variety of chiral olefins.
Although the method was only tested on olefins bearing
a chiral center adjacent to the double bond, its possibly
wider scope and ramifications are currently under
investigation.
(13) These salts could be either formed directly in the NMR tube,
by mixing stoichiometric amounts of chiral diamine and silver nitrate
or triflate, or prepared and stored separately in larger amounts. The
crude adducts can be obtained by mixing stoichiometric amounts of
silver salt (AgNO3 or AgOTf) and chiral diamine in dichloromethane
solution and successive evaporation of the solvent. In the case of the
nitrate salt a cleaner product could be obtained by bubbling ethylene
in the solution and precipitating the ethylene complex with pentane.
Upon drying under vacuum (0.1 mmHg) at 40 °C, ethylene was lost
and the pure [((N-N))Ag]NO3 salt was obtained. The corresponding
triflate salt does not lose ethylene under vacuum.
(14) Solvent and counterion effects can be rationalized more likely
as a consequence of olefin displacement equilibria rather than ion-
pair formation, since the switch to a supposedly more coordinating
anion moves all the chemical shifts of both enantiomers toward those
of the free olefin. Indeed, in the case of hydrocarbon olefins, such
equilibria are independently evidenced by the partial olefin loss when
diethyl ether rather than pentane is used in the precipitation of the
complex8 and by the loss of ethylene from the complex [(N-N)Ag(C2H4)]-
NO3 when drying it under vacuum.13
Ack n ow led gm en t. We thank the CIMCF of the
Universita` di Napoli Federico II for access to the NMR
facilities and the MIUR (Grant No. PRIN 2002-031332)
for financial support.
Su p p or tin g In for m a tion Ava ila ble: A table giving 1H
NMR shift differences between olefin enantiomers as affected
by solvent and counterion. This material is available free of
charge via the Internet at http://pubs.acs.org.
OM0341653