Evaluation of a chiral cubane-based Schiff base ligand in asymmetric catalysis reactions

Article abstract of DOI:10.3762/bjoc.8.207

Recently, a novel chiral cubane-based Schiff base ligand was reported to yield modest enantioselectivity in the Henry reaction. To further explore the utility of this ligand in other asymmetric organic transformations, we evaluated its stereoselectivity i

Full text of DOI:10.3762/bjoc.8.207

Evaluation of a chiral cubane-based Schiff base
ligand in asymmetric catalysis reactions
Kyle F. Biegasiewicz1, Michelle L. Ingalsbe1, Jeffrey D. St. Denis2,
James L. Gleason2, Junming Ho3, Michelle L. Coote3, G. Paul Savage4
and Ronny Priefer*1,5
Letter
Open Access
Address:
Beilstein J. Org. Chem. 2012, 8, 1814–1818.
1Department of Chemistry, Biochemistry, and Physics, Niagara
University, NY 14109, USA, 2Department of Chemistry, McGill
University, Montreal, QC, H3A 2K6, Canada, 3ARC Centre of
Excellence for Free-Radical Chemistry and Biotechnology, Research
School of Chemistry, Australian National University, Canberra ACT
0200, Australia, 4CSIRO Materials Science and Engineering, Clayton
South MDC 3169, Australia and 5College of Pharmacy, Western New
England University, Springfield, MA 01119, USA
doi:10.3762/bjoc.8.207
Received: 09 August 2012
Accepted: 19 September 2012
Published: 22 October 2012
Associate Editor: P. R. Schreiner
© 2012 Biegasiewicz et al; licensee Beilstein-Institut.
License and terms: see end of document.
Email:
Ronny Priefer* - ronny.priefer@wne.edu
* Corresponding author
Keywords:
chiral ligand; cubane; M06L and B3LYP calculations; Michael addition
Abstract
Recently, a novel chiral cubane-based Schiff base ligand was reported to yield modest enantioselectivity in the Henry reaction.
To further explore the utility of this ligand in other asymmetric organic transformations, we evaluated its stereoselectivity in
cyclopropanation and Michael addition reactions. Although there was no increase in stereocontrol, upon computational evaluation
using both M06L and B3LYP calculations, it was revealed that a pseudo six-membered ring exists, through H-bonding of a cubyl
hydrogen to the copper core. This decreases the steric bulk above the copper center and limits the asymmetric control with this
ligand.
Introduction
Since the initial synthesis of cubane in 1964 by Eaton and Cole (MAO) inactivators [8-10]. Cubanes have also shown a propen-
[1,2], numerous studies have been undertaken on its derivatives: sity to undergo cage opening. In particular, syn-tricyclooctadi-
Nitrated cubanes are remarkably explosive [3,4]; cubylamines enes are formed when rhodium(I) salts are introduced [11],
possess antiviral activity [5]; and cubylamides have been shown while with silver(I) or palladium(II) catalysts, cuneane is
to be P2X7 receptor antagonists [6]; whereas other cubane obtained [12]. Spontaneous cage opening has been observed
derivatives were examined as narcotic antagonists against both with cubanol yielding vinylcyclobutenylketene [13,14], whereas
μ and ĸ receptors [7], as well as being monoamine oxidase dicubyl disulfide is remarkably stable [15]. More recently,
1814

Beilstein J. Org. Chem. 2012, 8, 1814–1818.
4-iodo-1-vinylcubane was shown to undergo cage opening/ Results and Discussion
rearrangement to form 4-vinyl-trans-β-iodostyrene [16,17], We began by initially evaluating this cubane-based ligand with
whereas 1-iodocubane-4-carboxaldehyde undergoes cage cyclopropanation reactions. When no chiral ligand was added
opening/fragmentation to afford benzaldehyde, which further there was a 2.6:1 ratio of trans to cis products with no ee
reacts to give benzyl benzoate [18].
control. We then introduced our cubane-based chiral ligand 1 to
our cyclopropanation protocol with four different copper
Recently, we synthesized the first cubane-based Schiff base sources (Table 1). The highest ee value of 14% was found with
ligand (Figure 1) and screened it in the Henry reaction in the the use of Cu(I) triflate tetrakisacetonitrile as catalyst. For the
synthesis of β-nitroalcohols [19]. The cubyl moiety can be reaction with Cu(I) chloride, values of only 1% ee were
considered a cross between a tert-butyl and a phenyl group. In obtained for both cis and trans products. In all reactions, the
fact, the C–H bond of cubane has been shown to have ~31% trans product was favored over the cis. Overall, this reaction
s-character [20], compared to 25% for a simple alkane and 33% was unsuccessful in obtaining high stereoselectivity, and thus
for an aromatic hydrogen. Due to the bulk of the cube it was we decided to switch to Michael addition with organomagne-
initially envisioned that there would be high stereocontrol; sium and organozinc reagents.
however, the stereoselectivity was modest-at-best with only the
highest ee value of 39% being achieved when copper(I) chlo- Since the copper source that produced the highest ee value with
ride was used at 65 °C. Therefore, we decided to examine this the cyclopropanation above was Cu(I) triflate tetrakisacetoni-
novel ligand further in the hope of increasing the stereoselec- trile, we decided to initially focus on this catalyst precursor. We
tivity in other organic transformations.
were pleased to observe an ee value of 16% in the Michael ad-
dition of EtMgBr to 2-cyclohexen-1-one at 0 °C in Et2O
(Table 2, entry 1). We next screened a variety of solvents in this
reaction. With both CH2Cl2 and THF the ee values signifi-
cantly dropped (Table 2, entry 2 and 3). As previously reported,
CuCl gave the best results with the Henry reaction [19]; hence,
we decided to evaluate this copper source. This, however, did
not yield any encouraging results with only a maximum ee
value of 4% when performed in Et2O (Table 2, entry 4). We
next evaluated a Cu(OTf) toluene complex, as well as
Cu(OTf)2; however, we only obtained a maximum value of
12% ee with Cu(OTf) 2 in Et2O (Table 2, entry 10). The use of
Figure 1: Structure of (1R,2R)-N,N’-bis[(4-iodocuban-1-yl)methylene]-
trans-1,2-diamino cyclohexane (1).
Table 1: Cyclopropanation with cubane ligand 1.
Entry
Catalyst precursor
Conv (%)a
cis/transb
eeb
eeb
cis (%)
trans (%)
1
2
3
4
Cu(OTf) toluene complex
Cu(OTf) tetrakisacetonitrile
CuCl
53
13
77
82
45:55
29:71
37:63
42:58
9
14
1
5
9
1
6
Cu(OTf)2
8
aThe conversion was determined by analysis of the 1H NMR spectra. bDetermined by GC analysis using a Chirasil-Dextrin CB column.
1815

Beilstein J. Org. Chem. 2012, 8, 1814–1818.
Table 2: Asymmetric ethyl addition to 2-cyclohexen-1-one under different conditions.
Entry
Catalyst precursor
Alkylating reagent
Solvent
Conv (%)a
ee (%)b
1
2
Cu(OTf) tetrakisacetonitrile
Cu(OTf) tetrakisacetonitrile
Cu(OTf) tetrakisacetonitrile
CuCl
EtMgBr
EtMgBr
EtMgBr
EtMgBr
EtMgBr
EtMgBr
EtMgBr
EtMgBr
EtMgBr
EtMgBr
EtMgBr
EtMgBr
Et2Zn
Et2O
CH2Cl2
THF
>99
89
16 (R)
<1 (S)
3 (R)
4 (S)
1 (S)
2 (R)
1 (R)
15 (S)
11 (R)
12 (S)
5 (S)
1 (S)
3 (S)
9 (R)
9 (S)
11 (S)
4 (S)
4 (S)
1 (S)
12 (S)
6 (S)
1 (S)
3
>99
>99
92
4
Et2O
5
CuCl
CH2Cl2
THF
6
CuCl
>99
>99
>99
94
7
Cu(OTf) toluene complex
Cu(OTf) toluene complex
Cu(OTf) toluene complex
Cu(OTf)2
Et2O
8
CH2Cl2
THF
9
10
11
12
13
14
15
16
17
18
19
20
21
22
Et2O
>99
>99
>99
86
Cu(OTf)2
CH2Cl2
THF
Cu(OTf)2
Cu(OTf) tetrakisacetonitrile
Cu(OTf) tetrakisacetonitrile
CuCl
Et2O
Et2Zn
CH2Cl2
Et2O
87
Et2Zn
>99
>99
>99
>99
>99
>99
97
CuCl
Et2Zn
CH2Cl2
THF
CuCl
Et2Zn
Cu(OTf) toluene complex
Cu(OTf) toluene complex
Cu(OTf)2
Et2Zn
Et2O
Et2Zn
CH2Cl2
Et2O
Et2Zn
Cu(OTf)2
Et2Zn
CH2Cl2
THF
Cu(OTf)2
Et2Zn
>99
aThe conversion was determined by analysis of the 1H NMR spectra. bDetermined by HPLC (OD Column, 0.5 mL/min, 99.7:0.3 hexanes/iPrOH) after
derivatization with (R,R)-1,2-diphenylethane-1,2-diol.
Et2Zn has also been used to provide excellent stereoselectivity Using both B3LYP and M06L density functional theory
in Michael addition reactions [21,22]. However, with our methods, we observed N–C–C–N dihedral angles of 65.0 and
cubane-based chiral ligand 1 we did not have this success. Our 62.7°, respectively for the ligand 1 on its own (Figure 2a).
best result with this anion source was with Cu(OTf)2 in Et2O When this was complexed with a Cu+1, however, the cyclo-
reaching an ee value of only 12% (Table 2, entry 20).
hexyl moiety retained its chair conformation, but the N–C–C–N
dihedral angles dropped to 49.7° and 48.5°, in the B3LYP and
At the onset we had anticipated much stronger results as the M06L calculations, respectively (Figure 2b). In addition, the
large bulky nature of the cube should likely block one side of copper is observed to exhibit either an agostic interaction [29]
the copper complex, thus hopefully increasing stereoselectivity. or a H-bond [30] with the “meta” cubyl hydrogens (with respect
Appropriate crystals for X-ray analysis were not obtained, thus to the iodine). The H…Cu bond lengths of 2.06 Å with M06L
we decided to look into computational simulations. On the basis and 2.29 Å with B3LYP calculations are well within the
of earlier assessment studies [23,24], we chose the M06L [25] required H-bonding length of <3.2 Å [31]. In addition, the
density functional theory method (and B3LYP [26] for compari- C…Cu lengths of 2.85 and 3.03 Å with M06L and B3LYP, res-
son) to locate the global minimum-energy structures for the pectively, were well within the required 4.0 Å limit [31]. This
ligands and their Cu(I) complexes. The computations employed produces pseudo six-membered rings having a C–H…Cu bond
the 6-31+G(d) basis set, and for iodine the LAN2DZdp basis set angle of 125.1° or 122.9° with M06L and B3LYP calculations,
[27] with an effective core potential was used instead of respectively. As Cu(I) is a late transition metal in a low oxi-
6-31+G(d). All calculations were performed with Gaussian09 dation state [32], the H…Cu bond length is shorter than that of
[28].
C…Cu [27], and the C–H…Cu bond angle is >100° [33], it can
1816

Beilstein J. Org. Chem. 2012, 8, 1814–1818.
Figure 2: M06L DFT global minima for (a) (1R,2R)-N,N’-bis[(4-iodocuban-1-yl)methylene]-trans-1,2-diaminocyclohexane (1) and (b) Cu+1 complex
with ligand 1.
be stated that the H…Cu interaction is a true intermolecular Acknowledgements
multicenter hetero-acceptor hydrogen bond as opposed to an The authors thank the Niagara University Academic Center for
intermolecular pseudo-agostic bond. Cubyl hydrogens partici- Integrated Science and the Rochester Academy of Science for
pating in H-bonding have been reported previously with their financial support. MLI would like to thank the Barbara S.
nitrocubanes [34], as well as with dicubyl vic-disulfone [35]. Zimmer Memorial Research Award for financial aid. MLC
From the computational results it would appear that the cubes gratefully acknowledges generous allocations of supercom-
play very little role in blocking either side for selective coordi- puting time from the Australian National Computational Infra-
nation with the copper. In fact, it would appear that the very structure, support from the Australian Research Council under
modest selectivity is due to the axial hydrogens on the cyclo- its Centers of Excellence program, and an ARC Future Fellow-
hexyl moiety since the copper is best described as being ship. RP would also like to thank Western New England
strained square planar with a N–Cu–H bond angle of 93.7° for University, College of Pharmacy for generous financial support.
M06L and 91.0° for B3LYP.
References
1. Eaton, P. E.; Cole, T. W. J. Am. Chem. Soc. 1964, 86, 962.
Conclusion
doi:10.1021/ja01059a072
We obtained slight stereoselectivity for both cyclopropanation
2. Eaton, P. E.; Cole, T. W. J. Am. Chem. Soc. 1964, 86, 3157.
as well as Michael addition. A maximum ee value of 16% was
doi:10.1021/ja01069a041
observed when Michael addition was performed with EtMgBr
3. Eaton, P. E.; Zhang, M.-X.; Gilardi, R.; Gelber, N.; Iyer, S.;
at 0 °C in Et2O. The poor stereoselectivity is explained compu-
Surapaneni, R. Propellants, Explos., Pyrotech. 2002, 27, 1.
tationally by the lack of steric hindrance on either face of the
copper complex. In addition, H-bonding with cubyl hydrogens
and the copper core yielded a pseudo six-membered ring, which
decreased the N–C–C–N dihedral angle.
doi:10.1002/1521-4087(200203)27:1<1::AID-PREP1>3.0.CO;2-6
4. Zhang, M.-X.; Eaton, P. E.; Gilardi, R. Angew. Chem., Int. Ed. 2000,
39, 401.
doi:10.1002/(SICI)1521-3773(20000117)39:2<401::AID-ANIE401>3.0.
CO;2-P
5. Camps, P.; Duque, M. D.; Vázquez, S.; Naesens, L.; De Clercq, E.;
Sureda, F. X.; López-Querol, M.; Camins, A.; Pallàs, M.;
Prathalingam, S. R.; Kelly, J. M.; Romero, V.; Ivorra, D.; Cortés, D.
Bioorg. Med. Chem. 2008, 16, 9925. doi:10.1016/j.bmc.2008.10.028
6. Gunosewoyo, H.; Guo, J. L.; Bennett, M. R.; Coster, M. J.; Kassiou, M.
Bioorg. Med. Chem. Lett. 2008, 18, 3720.
Supporting Information
Supporting Information File 1
Gaussian archives of
(1R,2R)-N,N’-bis[(4-iodocuban-1-yl)methylene]-trans-1,2-
diaminocyclohexane (1) and Cu+1 complex with ligand 1.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-8-207-S1.pdf]
doi:10.1016/j.bmcl.2008.05.062
7. Cheng, C.-Y.; Hsin, L.-W.; Lin, Y.-P.; Tao, P.-L.; Jong, T.-T.
Bioorg. Med. Chem. 1996, 4, 73. doi:10.1016/0968-0896(95)00165-4
8. Zhou, J. J. P.; Li, J.; Upadhyaya, S.; Eaton, P. E.; Silverman, R. B.
J. Med. Chem. 1997, 40, 1165. doi:10.1021/jm9606249
1817

Beilstein J. Org. Chem. 2012, 8, 1814–1818.
9. Silverman, R. B.; Zhou, J. J. P.; Eaton, P. E. J. Am. Chem. Soc. 1993,
115, 8841. doi:10.1021/ja00072a048
License and Terms
10.Silverman, R. B. Acc. Chem. Res. 1995, 28, 335.
doi:10.1021/ar00056a003
This is an Open Access article under the terms of the
Creative Commons Attribution License
11.Cassar, L.; Eaton, P. E.; Halpern, J. J. Am. Chem. Soc. 1970, 92,
3515. doi:10.1021/ja00714a075
(http://creativecommons.org/licenses/by/2.0), which
permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
12.Eaton, P. E.; Cassar, L.; Halpern, J. J. Am. Chem. Soc. 1970, 92,
6366. doi:10.1021/ja00724a061
13.Cole, T. W., Jr. Ph.D. Thesis, University of Chicago, 1966.
14.Hormann, R. E. Ph.D. Thesis, University of Chicago, 1987.
15.Priefer, R.; Lee, Y. J.; Barrios, F.; Wosnick, J. H.; Lebuis, A.-M.;
Farrell, P. G.; Harpp, D. N.; Sun, A.; Wu, S.; Snyder, J. P.
J. Am. Chem. Soc. 2002, 124, 5626. doi:10.1021/ja025823y
16.Carroll, V. M.; Harpp, D. N.; Priefer, R. Tetrahedron Lett. 2008, 49,
2677. doi:10.1016/j.tetlet.2008.02.161
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
(http://www.beilstein-journals.org/bjoc)
The definitive version of this article is the electronic one
which can be found at:
17.Griffiths, J. R.; Tsanaktsidis, J.; Savage, G. P.; Priefer, R.
Thermochim. Acta 2010, 499, 15. doi:10.1016/j.tca.2009.10.015
18.Heaphy, P. J.; Griffiths, J. R.; Dietz, C. J.; Savage, G. P.; Priefer, R.
Tetrahedron Lett. 2011, 52, 6359. doi:10.1016/j.tetlet.2011.09.037
19.Ingalsbe, M. L.; St Denis, J. D.; Gleason, J. L.; Savage, G. P.;
Priefer, R. Synthesis 2010, 98. doi:10.1055/s-0029-1217083
20.Della, E. W.; Hine, P. T.; Patney, H. K. J. Org. Chem. 1977, 42, 2940.
doi:10.1021/jo00437a040
doi:10.3762/bjoc.8.207
21.Shibata, N.; Yoshimura, M.; Yamada, H.; Arakawa, R.; Sakaguchi, S.
J. Org. Chem. 2012, 77, 4079. doi:10.1021/jo300472r
22.Matsumoto, Y.; Yamada, K.-i.; Tomioka, K. J. Org. Chem. 2008, 73,
4578. doi:10.1021/jo800613h
23.Zhao, Y.; Truhlar, D. G. Theor. Chem. Acc. 2008, 120, 215.
doi:10.1007/s00214-007-0310-x
24.Zhao, Y.; Truhlar, D. G. Acc. Chem. Res. 2008, 41, 157.
doi:10.1021/ar700111a
25.Zhao, Y.; Truhlar, D. G. J. Chem. Phys. 2006, 125, 194101.
doi:10.1063/1.2370993
26.Becke, A. D. J. Chem. Phys. 1993, 98, 5648. doi:10.1063/1.464913
27.Wadt, W. R.; Hay, P. J. J. Chem. Phys. 1985, 82, 284.
doi:10.1063/1.448800
28.Gaussian 09, Revision A.1; Gaussian, Inc.: Wallingford CT, 2009.
29.Brookhart, M.; Green, M. L. H. J. Organomet. Chem. 1983, 250, 395.
doi:10.1016/0022-328X(83)85065-7
30.Thakur, T. S.; Desiraju, G. R. Chem. Commun. 2006, 552.
doi:10.1039/b514427b
31.Jeffrey, G. A. An Introduction to Hydrogen Bonding; Oxford University
Press: New York, 1997.
32.Braga, D.; Grepioni, F.; Desiraju, G. R. Chem. Rev. 1998, 98, 1375.
doi:10.1021/cr960091b
33.Braga, D.; Grepioni, F.; Tedesco, E.; Biradha, K.; Desiraju, G. R.
Organometallics 1997, 16, 1846. doi:10.1021/om9608364
34.Zhou, G.; Zhang, J.-L.; Wong, N.-B.; Tian, A. J. Mol. Struct. 2003, 639,
43. doi:10.1016/j.theochem.2003.07.007
35.Priefer, R.; Martineau, E.; Harpp, D. N. J. Sulfur Chem. 2007, 28, 529.
doi:10.1080/17415990701684701
1818