A highly diastereoselective [2,3]-sigmatropic N,O rearrangement

Article abstract of DOI:10.1039/a905981d

Lithium (E)-N-benzyl-O-(4-methoxy-4-phenylbut-2-enyl)-hydroxylamide undergoes a highly diastereoselective rearrangement via a chelated transition state, to afford after reduction, syn-3-benzylamino-4-methoxy-4-phenylbut-1-ene as a single diastereoisomer.

Full text of DOI:10.1039/a905981d

A highly diastereoselective [2,3]-sigmatropic N,O rearrangement
Steven D. Bull,a Stephen G. Davies,*a Simon Jones,a Jacqueline V. A. Ouzman,a Anne J. Pricea and David J.
Watkinb
a
The Dyson Perrins Laboratory, University of Oxford, South Parks Road, Oxford, UK OX1 3QY.
E-mail: steve.davies@chemistry.ox.ac.uk.
Chemical Crystallography Laboratory, University of Oxford, 9 Parks Road, Oxford, UK, OX1 3PD
b
Received (in Liverpool, UK) 20th July 1999, Accepted 15th September 1999
Lithium (E)-N-benzyl-O-(4-methoxy-4-phenylbut-2-enyl)-
hydroxylamide undergoes a highly diastereoselective re-
arrangement via a chelated transition state, to afford after
pathway which proceeds via a chelated transition state would
result in the syn-diastereoisomer 8 (Scheme 4).
reduction,
syn-3-benzylamino-4-methoxy-4-phenylbut-
1-ene as a single diastereoisomer.
Intramolecular sigmatropic rearrangements have found wide-
spread use in synthetic organic chemistry, primarily due to the
high selectivities observed in these transformations.1 We have
recently reported on a novel intramolecular [2,3]-rearrangement
of N-benzyl-O-allylic hydroxylamines 1 to afford N-benzyl-N-
hydroxyallylamines 2, which may be reduced to the correspond-
ing N-benzyl-N-allylamines 3 in good yield (Scheme 1).2 The
transition state of this N,O rearrangement may be compared
with that of the [2,3]-Wittig rearrangement;3 deprotonation of 1
affords a lithium amide which rearranges through an envelope
like transition state.
Scheme 2 Reagents and conditions: i, BuLi, THF, 278 °C.
Scheme 1 Reagents and conditions: i BuLi, THF; ii, Zn, aq. HCl.
Previous investigations into the synthetic utility of the
[2,3]-Wittig rearrangement4 have revealed that allylic ethers
with stereogenic centres bearing a heteroatom substituent
adjacent to the migration terminus have the capacity to undergo
diastereoselective rearrangement.5 For example, deprotonation
of allylic ether 4 with BuLi in THF at 278 °C affords the
rearranged product 5, containing two new stereogenic centres,
in 66% de (Scheme 2)6. Facial selectivity in this case is
controlled via a transition state where the carbanion attacks
antiperiplanar to the heteroatom via a conformation which
directs the allylic hydrogen on the original stereogenic centre to
the ‘inside’ site.
Scheme 3
This type of stereoelectronic effect might also operate to
control facial selectivity during the [2,3]-N,O rearrangement of
the lithium anion of (E)-N-benzyl-O-(4-methoxy-4-phenylbut-
2-enyl)hydroxylamine 6, however in contrast to the Wittig
rearrangement, in this case the possibility of chelation control is
also present. If N,O rearrangement of the lithium anion of 6
proceeds via a transition state where facial selectivity is
determined by stereoelectronic effects, then the anti-diastereo-
isomer 7 will be formed (Scheme 3), while a rearrangement
Scheme 4
Chem. Commun., 1999, 2079–2080
This journal is © The Royal Society of Chemistry 1999
2079

Thus (E)-N-benzyl-O-(4-methoxy-4-phenylbut-2-enyl)hy-
droxylamine 6 was prepared from racemic methyl O-me-
thylmandelate 9 via our previously described synthetic protocol
for this class of hydroxylamine.2 Methyl O-methylmandelate 9
was reduced with DIBAL-H in toluene at 278 °C and the
resulting aldehyde treated in situ with ethoxycarbonylmethyl-
ene(triphenyl)phosphorane to afford the a,b-unsaturated ester
10 in an unoptimised 53% yield. Reduction of ester 10 with
DIBAL-H in toluene gave allylic alcohol 11 in 80% yield,
which was treated with NBS in the presence of PPh3 to afford an
unstable allylic bromide 12. Subsequently, the crude reaction
product of the bromination reaction was treated with the
potassium anion of syn-benzaldehyde oxime to afford oxime 13
in an overall 45% yield from allylic alcohol 11. Reduction of
oxime 13 with pyridine·borane/HCl gave the desired rearrange-
ment substrate (±)-(E)-N-benzyl-O-(4-methoxy-4-phenylbut-
2-enyl)hydroxylamine 6 in 57% yield (Scheme 5).
Fig. 1 X-Ray crystal structure of the hydrated HCl salt of syn-(3RS,4RS)-
14.
(1H, d, J 13.2, NHCH2), 4.07 (1H, d, J 8.2, MeOCH), 4.93 (1H, d, J 17.2,
CHNCH2), 5.03 (1H, d, J 10.4, CHNCH2), 5.48–5.56 (1H, m, CHNCH2),
7.23–7.35 (10H, m, ArCH); dC(100 MHz, CDCl3) 51.2 (NHCH2Ph), 56.8
(OCH3), 66.9 (NHCHCHNCH2), 86.6 (PhCHOMe), 118.6 (CHNCH2),
126.7, 127.8, 127.9, 128.0, 128.1, 128.3 (10 3 ArCH), 136.7 (CHNCH2),
138.9 (ipso-ArC), 140.5 (ipso-ArC); m/z (APCI+) 323 (13%), 269 (12), 268
(100, MH+), 237 (13), 236 (82, M+ 2 OMe) (HRMS: calc. for C18H21NO,
268.1701; Found, 268.1706).
‡ Crystal data for 14·HCl·H2O: C18H24ClNO2, M = 321.84, monoclinic,
space group P1 21/n 1, a = 6.403(1), b = 27.046(1), c = 10.252(1) Å, b =
97.85(2)°, V = 1758.8 Å3, T = 180 K, Z = 4, Dc = 1.21 g cm23, T = 180
K, m(Mo-Ka) = 0.22 mm21, 3109 independent reflections were measured,
of which 2050 were used, R = 0.11, RW = 0.16. Rint = 0.08. The sample
was one of many pieces cut from clear plate-like crystals. Although the cut
samples remained clear, the diffraction patterns showed that they were
always severely damaged by shearing parallel to the large face during the
cutting. The final sample was obtained by repeatedly shaving very thin
slices away from the edges of the original large crystal. The best obtainable
diffraction pattern did not represent a simple single crystalline sample. Data
extraction from the 90 images (180 degrees) collected on a Nonius DIP2000
diffractometer were complicated by the presence of more than one
reciprocal lattice. Reflections from the strongest lattice were used as the
basis for the structure analysis, but were inevitably contaminated by data
from the weaker lattice. We could not determine a valid twin law relating the
two lattices—the sample was probably polycrystalline. The weakest data
showed the greatest discrepancy between Fo and Fc, presumably because
the accidental overlap of a strong component of the minor lattice on a weak
component of the strong lattice had a more damaging effect than the inverse.
Data with I < 6 s (I) were therefore excluded from the refinement. The
value of ‘6’ is subjective, but was chosen by looking at the residual
distribution so as to preserve as many ‘fair’ reflections as possible, and at the
same time reject as many ‘suspect’ reflections as possible. Only one of the
water hydrogen atoms could be located. CCDC 182/1415. See http:
//www.rsc.org/suppdata/cc/1999/2079/ for crystallographic data in .cif
format.
Scheme 5 Reagents and conditions: i, DIBAL-H, toluene, 278 °C, then
Ph3PNCHCO2Et; ii, DIBAL-H, toluene, 278 °C; iii, NBS, PPh3, CH2Cl2;
iv, PhCHNNOK, THF; v, pyridine·BH3, EtOH, HCl.
Treatment of hydroxylamine 6 with 1.1 equiv. of BuLi in
THF at 278 °C, followed by warming to room temperature over
1 h resulted in complete [2,3]-rearrangement to afford a single
diastereoisomer of 3-benzyl(hydroxy)amino-4-methoxy-4-phe-
1
nylbut-1-ene 8 in 94% conversion as determined by H NMR
spectroscopic analysis of the crude reaction mixture. Sub-
sequent reduction of the unstable N-hydroxy compound 8 to
syn-3-benzylamino-4-methoxy-4-phenylbut-1-ene 14 with zinc
in aqueous hydrochloric acid was achieved in 63% isolated
yield (Scheme 6).†
Scheme 6 Reagents and conditions: i BuLi, THF, 278 to 25 °C; ii, Zn, aq.
HCl.
1 S. M. Roberts, in Comprehensive Functional Group Transformations, ed.
A. R. Katritzky, O. Meth-Cohn and C.W. Rees, Pergamon, Oxford, 1995,
vol. 1, p. 404.
2 S. G. Davies, S. Jones, M. A. Sanz, F. C. Teixeira and J. F. Fox, Chem.
Commun., 1998, 2235.
X-Ray crystallographic analysis of the crystalline HCl salt of
syn-3-benzylamino-4-phenylbut-1-ene 14 clearly revealed that
[2,3]-rearrangement of 6 had occurred to afford syn-8 where the
relative stereochemistry of the two newly formed stereogenic
centres was (3RS,4RS) (vide infra) (Fig. 1).‡
The syn-selectivity of diastereoisomer 14 found during
rearrangement of 6 is clearly in accord with the chelation
control transition state model described in Scheme 4, rather than
the stereoelectronic model described in Scheme 3.
In conclusion, (E)-N-benzyl-O-(4-methoxy-4-phenylbut-
2-enyl)hydroxylamine 6 undergoes a highly diastereoselective
rearrangement to afford, after reduction, syn-3-benzylamino-
4-methoxy-4-phenylbut-1-ene 14 containing two new stereo-
genic centres with complete diastereoselectivity via a chelated
transition state.
3 Y. D. Wu, K. N. Houk and J. A. Marshall, J. Org. Chem., 1990, 55,
1421.
4 For examples of the synthetic utility of the [2,3]-Wittig rearrangement,
see T. Nakai and K. Mikami, Chem. Rev., 1986, 86, 885; ‘The Wittig
Rearrangement’ in C-C s Bond Formation, ed. G. Pattenden, vol. 3 of
Comprehensive Organic Synthesis ed. B. M. Trost and I. Fleming,
Pergamon, Oxford, 1990, p. 975.
5 K. Mikami and T. Nakai, Synthesis, 1991, 594; R. Brückner and H.
Priepke, Angew. Chem., 1988, 27, 278; H. Priepke and R. Brückner,
Chem. Ber., 1990, 123, 153.
6 R. Brückner, Chem. Ber., 1989, 122, 193; E. Nakai and T. Nakai,
Tetrahedron Lett., 1988, 29, 4587.
7 For an example where the diastereoselectivity observed for a [2,3]-Wittig
rearrangement has been rationalised via a chelated transition state, see
S. W. Scheuplein, A. Kusche, R. Brückner and K. Harms, Chem. Ber.,
1990, 123, 917.
Notes and references
† Selected data for 14: mp 41–43 °C; dH (400 MHz, CDCl3) 3.21 (3H, s,
OCH3), 3.31 (1H, t, J 8.2, CHCHNCH2), 3.62 (1H, d, J 13.2, NHCH2), 3.87
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Chem. Commun., 1999, 2079–2080