Zirconium catalysed enantioselective hydroamination/cyclisation

Article abstract of DOI:10.1039/b401493f

A chiral zirconium alkyl cation catalyses the cyclisation of certain aminoalkenes with enantioselectivity up to 82%, the highest thus far observed for such a process.

Full text of DOI:10.1039/b401493f

Zirconium catalysed enantioselective hydroamination/cyclisation†
Paul D. Knight, Ian Munslow, Paul N. O’Shaughnessy and Peter Scott*
Department of Chemistry, University of Warwick, Coventry, UK. E-mail: peter.scott@warwick.ac.uk;
Fax: 024 7657 2710; Tel: 024 7652 3238
Received (in Cambridge, UK) 2nd February 2004, Accepted 20th February 2004
First published as an Advance Article on the web 5th March 2004
A chiral zirconium alkyl cation catalyses the cyclisation of
certain aminoalkenes with enantioselectivity up to 82%, the
highest thus far observed for such a process.
Zr–C(30) 3.036 Å]. NMR spectra were also consistent with cis-b
configuration.
Cyclisation of aminoalkenes via hydroamination of the double
bond is a very attractive approach for the synthesis of N-
heterocycles.1 Organolanthanide catalysts have provided the only
examples thus far of the enantioselective variant of this reaction;
Marks’ original report based on chiral ansa-metallocenes,2 which
gave up to 74% ee, is yet to be improved upon in terms of
enantioselectivity, despite intense efforts from several groups.3 It
would seem that as a result of the large size and the geometrical
flexibility of organolanthanide compounds, sufficiently precise
control of the metal coordination sphere is difficult to achieve.4 The
group 4 metals could fare better in this respect, but have thus far
only been shown to catalyse the rather less thermodynamically-
challenging addition of amines to alkynes and allenes to generate
(achiral) imines.5 We postulated that the group 4 alkyl cations, the
active species in Ziegler-type alkene polymerisations,6 may be
more potent as a result of their enhanced Lewis acidity. Cationic (or
cation-like) metallocene catalysts have also been used in a limited
number of organic transformations,7 including Buchwald’s en-
antioselective hydrogenation of alkenes.8
The reaction between H2L2 and [Zr(CH2Ph)4] gave a single
complex species. Two pairs of AB doublets from diastereotopic
methylene groups were apparent in the 1H NMR spectrum, but only
one Zr–CH2Ph group was present. The second methylene group
arises from a metallated N–Me group (i.e. N–CH2–Zr). Assuming
that the first formed species in this reaction is the expected
[ZrL2(CH2Ph)2] (1, Scheme 1), then it seems that close proximity
to the zirconium centre of a relatively acidic N–Me group (vide
supra) has encouraged protonolysis of one Zr–CH2Ph bond to form
the metallacycle [Zr(L2A)(CH2Ph)] 2. The proton source
[PhNMe2H][B(C6F5)4] reacted cleanly with 2 to give the desired
We have recently reported3 the development of chiral aminophe-
nol proligands H2L1 and H2L2 as robust alternatives to the
analogous Schiff-bases.9 Reactions of these proligands with
[Zr(NMe2)2Cl2(THF)2] in dichloromethane generated the colour-
less complexes [ZrL1Cl2] and [ZrL2Cl2]. The former was shown by
X-ray crystallography to adopt the trans structure, which is unlikely
to be of use in catalyses such as that under study here where
mutually cis coordination sites are required. We thus focussed our
efforts on [ZrL2Cl2] which gave the favourable10 unsymmetrical
cis-b structure as shown in Fig. 1.‡ It is interesting to note that the
coordinated amine groups in [ZrL2Cl2] have mutually opposite
configurations within the same molecule and that the N–Me groups
are in close proximity to the metal centre [Zr–C(15) 3.498 Å and
† Electronic Supplementary Information (ESI) available: experimental
details and characterising data for complexes and substrates, catalytic
protocol, determination of ee, crystal data for [ZrL2Cl2]. See http://
www.rsc.org/suppdata/cc/b4/b401493f/
Fig. 1 Molecular structure of [ZrL2Cl2]. Selected bond lengths (Å) and
angles (°): Zr–O(1) 1.949(3), Zr–O(2) 1.977(3), Zr–Cl(1) 2.421(15), Zr–
Cl(2) 2.443(15), Zr–N(1) 2.541(4), Zr–N(2) 2.483(4), O(1)–Zr–O(2)
98.58(15), N(1)–Zr–N(2) 88.43(13), Cl(1)–Zr–Cl(2) 92.91(5)
Scheme 1 Synthesis of [ZrL2CH2Ph][B(C6F5)4] 3.
894
C h e m . C o m m u n . , 2 0 0 4 , 8 9 4 – 8 9 5
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

Table 1 Hydroamination/cyclisation catalysed by 3a
were in any event unable to determine the ee. N-Methyl-
2-allylaniline (entry 5) was cyclised quite efficiently, and although
the ee obtained was modest, this appears to be the first reported
enantioselective cyclisation of this type of substrate.
Entry
1
Substrate
Product
t/hc
ee (%)d
64
4
On the basis that this reactions is proceeding by a similar
mechanism (Scheme 2) to that proposed by Marks2 for the
lanthanide catalyses, then a critical issue is the binding of the alkene
group to the metal in the amido complex I. This determines the
geometry of insertion into the amide–metal bond and thus the
configuration of the stereogenic centre in the resultant heterocycle.
Strong olefin activation, as well as efficient expression of chirality
from the ligand to the active sites are required. It would seem that
our employment of the zirconium alkyl cation in 3 here has
provided the former and to a great extent the latter. For primary
amine substrates however, the cationic nature of the catalyst species
means that amido NH deprotonation is possible. The resultant
neutral imido species II, similar to that implicated in aminoalkyne
hydroamination,12 is unable to activate the alkene sufficiently for
insertion. We are currently addressing this problem.
2b
3
48
3
14
82
4
5
192
3
nd
20
a C6D5Br at 100 °C, ca. 10 mol% catalyst. b 5 mol% catalyst, 70 °C. 30%
alkene isomerisation product. c Time for 100% conversion of substrate.
d NMR analysis of (R)-(+)-Mosher’s acid salt (see ESI).
PS thanks EPSRC and BP Chemicals for support of this work.
Notes and references
‡ Crystal data: C51H66Cl2N2O2Zr,
M = 901.18, monoclinic, a =
22.7186(9), b = 10.2902(4), c = 20.7759(9) Å, b = 99.4450(10), U =
4791.1(3) Å3, T = 180 K, space group P2(1)/c, Z = 4, m(Mo-Ka) = 0.381
mm21, 30886 reflections measured, 11948 unique (Rint = 0.1341). Final R1
= 0.0842 [I > 2s(I)]. CCDC 230266. See http://www.rsc.org/suppdata/cc/
b4/b401493f/ for crystallographic data in .cif or other electronic format.
§ It is unclear as yet whether the co-product PhNMe2 is coordinated to the
metal centre in this product.
1 F. Pohlki and S. Doye, Chem. Soc. Rev., 2003, 21, 104; T. E. Müller and
M. Beller, Chem. Rev., 1998, 98, 675.
2 M. R. Gagné, C. L. Stern and T. J. Marks, J. Am. Chem. Soc., 1992, 114,
275; M. R. Douglass, M. Ogasawara, S. Hong, M. V. Metz and T. J.
Marks, Organometallics, 2002, 21, 283; M. A. Giardello, V. P.
Conticello, B. Laurent, M. R. Gagne and T. J. Marks, J. Am. Chem. Soc.,
1994, 116, 10241.
3 P. N. O’Shaughnessy, P. D. Knight, C. Morton, K. M. Gillespie and P.
Scott, Chem. Commun., 2003, 1770; P. N. O’Shaughnessy and P. Scott,
Tetrahedron Asymmetry, 2003, 14, 1979; S. Hong, S. Tian, M. V. Metz
and T. J. Marks, J. Am. Chem. Soc., 2003, 125, 14768; J. Collin, J.-C.
Daran, E. Schulz and A. Trifonov, Chem. Commun., 2003, 3048.
4 H. C. Aspinall, Chem. Rev., 2002, 102, 1807.
5 J. Seayad, A. Tillack, C. G. Hartung and M. Beller, Adv. Synth. Catal.,
2002, 344, 795; I. Bytschkov and S. Doye, Eur. J. Org. Chem., 2003,
935; C. Li, R. K. Thomson, B. Gillon, B. O. Patrick and L. L. Schafer,
Chem. Commun., 2003, 2462; Y. Shi, C. Hall, J. T. Ciszewski, C. Cao
and A. L. Odom, Chem. Commun., 2003, 586; C. Cao, Y. Shi and A. L.
Odom, J. Am. Chem. Soc., 2003, 125, 2880; I. Bytschkov and S. Doye,
Tetrahedron Lett., 2002, 43, 3715.
6 M. Bochmann, S. J. Lancaster, M. D. Hannant, A. Rodriguez, M.
Schormann, D. A. Walker and T. J. Woodman, Pure Appl. Chem., 2003,
75, 1183; E. Y.-X. Chen and T. J. Marks, Chem. Rev., 2000, 100,
1391.
7 K. H. Shaughnessy and R. M. Waymouth, J. Am. Chem. Soc, 1995, 117,
5873; G. A. Molander and C. P. Corrette, Tetrahedron Lett., 1998, 39,
5011; K. H. Shaughnessy and R. M. Waymouth, Organometallics,
1998, 17, 5728; A. D. Sadow and T. D. Tilley, Organometallics, 2003,
22, 3577.
Scheme 2 Possible mechanism for hydroamination/cyclisation catalysed by
3 (R = Me).
alkyl cation complex, orange [ZrL2(CH2Ph)][B(C6F5)4] 3 in situ.§
We were pleased to find that 3 showed no signs of decomposition
on heating to 100 °C overnight; a remarkable level of stability for
a non-metallocene.
Treatment of 3 with 10 equivalents of candidate aminoalkenes
containing primary amine groups led to no conversion to the
corresponding heterocycles (vide infra). Nevertheless, various
secondary amine substrates were found to undergo hydroamina-
tion/cylisation in the presence of chiral non-racemic [Zr[(S)-
L2](CH2Ph)][B(C6F5)4]. All catalyses gave 100% conversion
(Table 1).
1-(N-Methylamino)pent-4-ene (entry 1) gave a similar ee to the
best observed thus far for the primary amino analogue.2 Surpris-
ingly, the similar gem-dimethyl compound (entry 2) gave a
disappointing ee; we suspect that a different mechanism is in
operation for this substrate since it is the only one thus far which
undergoes significant double-bond isomerisation with this catalyst
(see ESI). The aminoalkene 1-(N-methylamino)-2,2-dimethylhex-
5-ene (entry 3) gave the highest ee thus far recorded for any
hydroamination/cyclisation reaction.11 The analogous p-methy-
oxybenzyl substituted amine (entry 4) cyclised much more slowly,
presumably as a result of steric protection of the N atom, and we
8 M. V. Troutman, D. H. Appella and S. L. Buchwald, J. Am. Chem. Soc.,
1999, 121, 4916.
9 K. M. Gillespie, E. J. Crust, R. J. Deeth and P. Scott, Chem. Commun.,
2001, 785; I. J. Munslow, K. M. Gillespie, R. J. Deeth and P. Scott,
Chem. Commun., 2001, 1638; P. R. Woodman, N. W. Alcock, I. J.
Munslow, C. J. Sanders and P. Scott, J. Chem. Soc., Dalton Trans.,
2000, 3340; P. D. Knight, A. J. Clarke, B. S. Kimberley, R. A. Jackson
and P. Scott, Chem. Commun., 2002, 352.
10 P. D. Knight and P. Scott, Coord. Chem. Rev., 2003, 242, 125.
11 P. W. Roesky and T. E. Müller, Angew. Chem., Int. Ed., 2003, 42,
2708.
12 I. Bytschkov and S. Doye, Eur. J. Org. Chem., 2003, 935.
C h e m . C o m m u n . , 2 0 0 4 , 8 9 4 – 8 9 5
895