Synthesis and characterization of 'calixsalens': A new class of macrocyclic chiral ligands

Article abstract of DOI:10.1039/a900018f

Template directed reaction of dialdehydes and (R,R)- or (S,S)-1,2-diaminocyclohexane affords a practical route to chiral, metal-free macrocyclic salen dimers which have a novel calixarene-like structure and show catalytic activity for enantioselective epo

Full text of DOI:10.1039/a900018f

Synthesis and characterization of ‘calixsalens’: a new class of macrocyclic
chiral ligands
Zengmin Li and Chet Jablonski*
Department of Chemistry, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada A1B 3X7.
E-mail: cjablons@morgan.ucs.mun.ca
Received (in Corvallis, OR, USA) 4th January 1999, Accepted 7th June 1999
Template directed reaction of dialdehydes and (R,R)- or
(S,S)-1,2-diaminocyclohexane affords a practical route to
chiral, metal-free macrocyclic salen dimers which have a
novel calixarene-like structure and show catalytic activity
for enantioselective epoxidation of unfunctionalized alkenes
in the presence of MnIII–NaOCl (aq.).
propriate dialdehyde (3a–d or 4), prepared from the correspond-
ing aldehydes.10 Three products, identified as the dimer 5d (m/z
893), along with the corresponding trimer (m/z 1339) and
tetramer, were isolated from condensation of dialdehyde 3d and
trans-(R,R)-(2)-1,2 diaminocyclohexane. Two major products
were obtained from cyclization of 3a–c with the (R,R)-diamine.
The higher TLC Rf product in each case was confirmed to be
macrocyclic dimer 6a–c (m/z 668, 725 and 837). Relatively
simple and similar 1H NMR spectra of the dimer and the
corresponding trimer or tetramer suggested a highly symmetric
structure. 13C NMR revealed seven low field signals assigned to
the four equivalent imine CNN carbons and six of the twenty-
four aromatic carbons of 5a–d. Consistent with overall D2
symmetry, four (5a), five (5b) or six (5c,d) high field 13C NMR
signals were observed for the remaining carbon atoms.
A single crystal X-ray study† of 5a·DMF confirms the D2
symmetric structure (Fig. 1) inferred from solution spectros-
copy. The four benzene rings of 5a·DMF form a well-defined
cavity and adopt a 1,3-dialternate conformation with a striking
calixarene-like11 structure, hence we have introduced the name
‘calixsalen’ to describe these macrocycles. The two opposing
face-to-face benzene rings are nearly coplanar and lie 7.57 Å
apart and, as a consequence of the preferred 1,3-dialternate
conformation, the hydroxy groups are twisted away from the
‘salen’ plane so that hydrogen-bonding between adjacent OH
groups is precluded.
Chiral Schiff base ligands are efficient chiral auxiliaries for a
wide range of enantioselective epoxidations.1 Our search
strategy for new asymmetric catalysts, particularly for asym-
metric epoxidation of unfunctionalized alkenes,1–4 has focussed
on development of chiral macrocycles bearing two salen-based
metal binding sites5 which can act co-operatively6a,7 within an
enzyme-like chiral cavity. This approach is based on the
expectation that non-covalent interactions,8 which are the sole
determinants of stereochemical outcome for enantioselective
reactions of unfunctionalized substrates,2a,9 can be maximized
within a chiral host–guest paradigm.6 The macrocycles reported
herein are simple chiral salen dimers (Scheme 1) containing two
tetradentate metal binding sites coupled by one- or four-atom
linking groups which determine ring size.
The 26- or 32-membered salen macrocycles 5 and 6 were
synthesized by template-induced cyclization (Scheme 1) of
trans-(R,R) or trans-(S,S)-1,2-diaminocyclohexane and an ap-
OH
In contrast, the ambient temperature 500 MHz 1H NMR
spectrum of the 32-membered salen macrocycle 6, obtained as
a single TLC band from cyclization of 4 with the (R,R)-diamine
(cf. Scheme 1), showed four imine signals (8.12, 8.10, 8.09 and
8.07 ppm) in a ratio of 2+4+8+30 which were assigned to four
slowly-interconverting conformers. NMR and mass spectral
(m/z 761) evidence are consistent with the dimeric structure 6.
13C NMR showed two imine carbon signals (164.74, 164.51
ppm) in an approximate ratio of 10+30 corresponding to the two
most stable conformers. Eleven pairs of 13C resonances for the
two major conformers, tentatively assigned as the D2 symmetric
1,3-alternate and C2 symmetric 1,2-alternate conformers in
slow exchange, were observed. Although a maximum of eleven
13C resonances are expected for the D2 symmetric 1,3-alternate
conformation, the 1,2-alternate or any of the remaining
O
R
i ( 3)
O
O
1
HO
Q
OH
OH
R
R
ii,iii ( 4)
O
3
a Q = CH2, R = H
b Q = CH2, R = Me
c Q = CH2, R = Pri
d Q = CH2, R = But
OH
4 Q = OCH2CH2O, R = H
2
iv
N
N
OH
HO
5a Q = CH2, R = H
b Q = CH2, R = Me
c Q = CH2, R = Pri
d Q = CH2, R = But
6 Q = OCH2CH2O, R = H
R
R
R
Q
Q
R
OH
N
HO
N
Scheme 1 Reagents and conditions: i, (CH2O)3, H2SO4, AcOH, 70 °C;
ii, NaH, (TsOCH2)2; iii, HCl; iv, 1,2-diaminocyclohexane, Ba(ClO4)2,
MeOH–THF.
Fig. 1 ORTEP representation (30% ellipsoids) for 5a·DMF (DMF and
hydrogen atoms removed for clarity).
Chem. Commun., 1999, 1531–1532
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conformations should show a total of 22 resonances. We
conclude that some degree of flexibility, made possible by the
ethylene glycol links, establishes a second, time-average C2
axis. Warming to 55 °C results in collapse of the two 13C imine
resonances into a single peak at 165.04 ppm, possibly as a result
of 1,3-alternate Ô 1,2-alternate exchange which becomes fast
on the NMR time scale.
comparison of the enantioselectivity of the bimetallic calixsalen
complexes reported in this work with the well characterized
Jacobsen catalysts. Aqueous NaOCl oxidation of styrene in the
presence of the brown dimanganese complex of 5d in CH2Cl2
gave only epoxide product with 52% ee in 63% isolated
chemical yield at 25 °C. This result compares favourably with
the best value of 59% ee at 23 °C in CH2Cl2 for a mononuclear
MnIII salen catalyst reported by Jacobsen.12
Although the solid state conformation of 5a·DMF appears ill-
disposed to provide two tetradentate salen coordination sites,
reaction with MnIII salts is facile. Addition of a solution of
Mn(OAc)3 to solutions of the salen dimers 5 or 6 caused an
immediate colour change from yellow to deep brown. An
electrospray mass spectrum of a methanolic solution of the dark
brown product obtained by treatment of 5d with Mn(OAc)3
showed strong peaks at m/z 1093 [(5d 24H)Mn2·2MeOH-
·CH2O]+, 1063 [(5d 24H)Mn2·2MeOH]+, 1045 [(5d
24H)Mn2·HCO2H]+, 999 [(5d 24H)Mn2]+ and 893 [5d]+,
consistent with the formation of a bimetallic complex.
Preliminary tests of the brown MnII macrocyclic salen
complexes as catalysts for the epoxidation of styrene, the most
challenging enantioselective version of this type of reaction thus
far,12 were conducted at room temperature (23 °C) using NaOCl
(aq) as terminal oxidant (Scheme 2). Both ring-opened
chloromethyl ether and epoxide products were obtained with
modest enantioselectivity (Scheme 2) in methanolic solvent.
Chemoselectivity responds to the steric requirements of the R
groups. For example, tert-butyl substituted macrocycle 5d gave
epoxide+chloro ether in the ratio 100+3 but only one product
(85–87% chemical yield), identified as 1-phenyl-1-chloro-
2-methoxy ethane by mass spectrometric analysis and compar-
ison of NMR data with 1-phenyl-1-methoxy-2-chloroethane
(obtained through direct chlorination of styrene in MeOH), was
isolated in the presence of unsubstituted dimer 5a or 6.
Interestingly, both epoxide and chlorinated products (chloro
ether or chlorohydrin) in a ratio of 10+1 are obtained with
catalyst 5b (R = CH3).
C. J. acknowledges the Natural Science and Engineering
Council of Canada (NSERC) for a grant in aid of research. Z. L.
acknowledges Memorial University for financial support. We
thank Professor M. McGlinchey and MacMaster University for
500 MHz NMR data reported for compound 6 and Mr David
Miller, Memorial University Crystallography Laboratory, for
determination of the molecular structure of 5a.
Notes and references
† Crystal data for 6a: C42H40O4N4·DMF, yellow, monoclinic, space group
P21/c (#14), a = 14.640(3), b = 25.679(4), c = 11.045(6) Å, b =
81.97(2)°, V = 4112(4) Å3, Z = 4, 5858 unique reflections, R = 0.077, Rw
= 0.045, GOF = 1.80. CCDC 182/1289.
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The ring opened products obtained were uniquely anti-
Markownikoff, hence Scheme 2 may have some important
synthetic applications.13 Reversed regioselective chlorination
of alkenes has previously been observed in alkoxychlorination
of allylamines with Wacker type catalysts14 but Markownikoff
addition was found for all other alkenes tested.
Unlike mononuclear salen catalysts,2a the enantioselectivity
of the macrocyclic MnIII–calixsalen systems reported in this
work appears unrelated to the steric requirements of the R
groups on the ortho position of the phenol in the salen frame
(Scheme 2). We therefore speculate that the observed enantio-
selectivity is controlled by host–guest intra-cavity inter-
actions.
The dimanganese complex isolated from ligand 5d, which
unlike that from 5a was soluble in CH2Cl2, allows direct
Cl
OMe
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8156.
6a, 7
Ph
MeOH–CH2Cl2
85–87% (38% ee)
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Soc., 1994, 116, 9333.
Cl
OMe
Mn(OAc)3
Ph
+
NaOCl (aq)
6b–d
O
Ph
MeOH–CH2Cl2
23 °C
Ph
32–67% (34–35% ee)
13 A. El-Qisairi, O. Hamed and P. M. Henry, J. Org. Chem., 1998, 63,
2790; J. Y. Lai, F. S. Wang, G. Z. Guo and L. X. Dai, J. Org. Chem.,
1993, 58, 6944; H. Nakamura, M. Sekido, M. Ito and Y. Yamamoto,
J. Am. Chem. Soc., 1998, 120, 6838.
O
6d
CH2Cl2
Ph
14 J. Y. Lai, X. X. Shi and X. Dai, J. Org. Chem., 1992, 57, 3485.
63% (52% ee)
Scheme 2
Communication 9/00018F
1532
Chem. Commun., 1999, 1531–1532