Decomplexation-nitroso Diels-Alder (NDA) approach to C,D-ring functionalisation for hippeastrine

Article abstract of DOI:10.1016/j.tetlet.2010.09.118

A tandem decomplexation-nitroso Diels-Alder (decomplexation-NDA) procedure has been shown to give the regiocontrol and stereocontrol needed for application in an organoiron-mediated synthesis of the alkaloid hippeastrine, using a selection of nitrosoarene

Full text of DOI:10.1016/j.tetlet.2010.09.118

Tetrahedron Letters 51 (2010) 6806–6809
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Tetrahedron Letters
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Decomplexation–nitroso Diels–Alder (NDA) approach to C,D-ring
functionalisation for hippeastrine
⇑
G. Richard Stephenson , Andrew M. Balfe, David L. Hughes, Richard D. Kelsey
School of Chemistry, University of East Anglia, Norwich NR4 7TJ, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
A tandem decomplexation–nitroso Diels–Alder (decomplexation–NDA) procedure has been shown to
give the regiocontrol and stereocontrol needed for application in an organoiron-mediated synthesis of
the alkaloid hippeastrine, using a selection of nitrosoarenes with functionality present to facilitate
removal of the arene after the NDA step.
Received 3 August 2010
Revised 26 August 2010
Accepted 24 September 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Organoiron
Nitroso Diels–Alder
Tandem reactions
Deprotection
Hippeastrine
The nitroso Diels–Alder (NDA) reaction1 has a long history2 but
is only recently becoming widely applied3–6 as a general method
for stereocontrolled organic synthesis. The intrinsic control of rel-
ative stereochemistry of C–N and C–O bond formation is a unique
advantage of NDA reactions (Fig. 1) as exemplified, for example, in
a recent application4 in an approach to the synthesis of stenine
(Fig. 1b),6 which like our work towards hippeastine7–9 (Fig. 1a) re-
quires regioselective C–N bond formation next to an alkyl substitu-
ent (R: see Fig. 2).10 For hippeastrine, we are developing an
intermolecular NDA with nitroso reagents that give good regiocon-
trol and show compatibility with a novel one-pot decomplexation–
NDA procedure9 to allow tricarbonyliron complexes11 to be em-
ployed directly as starting materials for the NDA step.12
from an X-ray study15 of a single NDA product, which was obtained
in 99% yield. Encouraged by the good prospects for efficient, regio-
controlled, high-yielding NDA cycloadditions, we have examined
(Scheme 1) the compatibility of 2-nitrosopyridine 8 with our
one-pot decomplexation–NDA method, using our initial model sys-
tem (2: R = Me, Ar = Ph) to study the regiocontrol. The outcome
was unexpected, as two regioisomeric products 5 and 6 were ob-
tained in a 1:2 ratio in 60% yield. The major product proved (COSY
1H NMR spectroscopy) to be 6, the opposite regioisomer to that
reported from 6-methyl-2-nitrosopyridine and 2-methylcyclo-
hexa-1,3-diene15 or from 2-nitrosopyridine and 2-(n-butyl)-cyclo-
hexa-1,3-diene.16
We turned instead to a revised approach using 4-nitroarenes
because the presence of the nitro group would also provide acti-
vation for removal of the arene by an SNAr process. The cycload-
In contrast to acylnitroso reagents,13 we have shown9 that aryl-
NDA with 2-methylcyclohexa-1,3-diene gave the correct regiocon-
trol and with a model complex (2: R = Me, Ar = Ph) we successfully
demonstrated good regio- and stereochemistry in the novel
decomplexation–NDA procedure. This result has now been con-
firmed with
a more advanced model complex [Fig. 2, box:
H
D
2
Me
A
N
O
C
3 H
R = CH2CH2OAc, Ar = C6H3(OCH2O)] which gave the required cyc-
loadduct 3 in 82% yield.
H
1 C4
H
H
2
N
D
N
3
1
1
O
O
OH
H
B
H
4
As an example with a removable aryl group, we chose 2-nitros-
opyridine reagents14 [dearylation is possible15 by N-tosylation,
quaternisation of the pyridine nitrogen and SNAr displacement
with methanolic NaOH(aq)] because the correct regiocontrol of
the cycloaddition with 2-methylcyclohexa-1,3-diene is known
4
B
O
O
OH
H
A
H
H
O
1,4-N,O pattern of stereocentres
(see ref. 4)
O
(a)
(b)
Hippeastrine (see ref. 9)
Stenine
Figure 1. The 1,4-relationship between C–N and C–O bonds at key stereocentres in
the C,D-rings of (a) hippeastrine and B,D rings of (b) stenine [for work towards
stenine using an acylnitroso cycloaddition (acyl-NDA), see Shea and co-workers;
Ref. 4].
⇑
Corresponding author. Tel.: +44 1603 592019; fax: +44 1603 592003.
E-mail address: g.r.stephenson@uea.ac.uk (G.R. Stephenson).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.09.118

G. R. Stephenson et al. / Tetrahedron Letters 51 (2010) 6806–6809
6807
AcO
OAc
R
AcO
Fe(CO)3
Me3NO
Ph
H
N
Fe(CO)3
5
4
O
O
4
O
N
6
O
3
1
Ar
O
O
8
O
O
N
2
H
2
1
O
O
7
3
1
O
R = CH2CH2OAc; Ar = C6H3(OCH2O)
one-pot decomplexation-NDA
Figure 2. (a) Proposed advanced intermediate 1 for an organoiron route to hippeastrine; (b) NDA cycloadduct 3 with the correct regiochemistry of 1,4-difunctionalisation in a
model system.
6
R
Ar' N=O
5
1
2
O
7
Ar
3
N
5
8
Ar'
N
R
method A
4
Ar
4
5
Me
Me3NO, Ar' N=O
method B
6
4
3
8
Fe(CO)3
Ar
N
2
O
7
R
1
Ar
6
2
O
O
O
O
N
N
N
N
NO2
N
O
=
N
Ar'
NO2
O
7
8
9
10
Scheme 1. Regio- and stereocontrol of NDA and tandem decomplexation–NDA
reactions (see Table 1).
Figure 3. ORTEP drawings of (a): 5 [Ar, R = H; Ar0 = 4-(C6H4)NO2] and (b): 5 [Ar,
R = H; Ar0 = 4-(C6H4)–OCH2-4-(C6H4)NO2].
dition between 4-nitro-1-nitrosobenzene 9 and cyclohexa-1,3-
diene has been described previously in 7% yield,17 using an
in situ generation of the nitroso reagent from 4-nitroaniline by
oxidation18 with H2O2 in the presence of a molybdenum catalyst,
so we opted instead to generate 4-nitro-1-nitrosobenzene19 by
the standard procedure20 converting 1,4-dinitrobenzene into the
nitroso reagent via the aryl hydroxylamine. NDA reaction (Meth-
od A) gave 5 (Ar, R = H; Ar0 = 4-(C6H4)NO2) in 92% yield (Table 1,
entry 1). We obtained an X-ray structure21 of this product
(Fig. 3a) which showed the arene pointing outwards from the
bicyclic system, equatorial with respect to the boat ring and cis
to the alkene group of 2-oxa-3-aza-bicyclo[2.2.2]oct-5-ene. In
the decomplexation–NDA reaction (Method B) with tricarbonyl-
iron complex 2 (Ar, R = H), cycloadduct 5 (Ar, R = H; Ar0 = 4-
(C6H4)NO2) was obtained in 58% yield (entry 2). The cycloadduct
was quaternised (Scheme 2) to form 11 as a 3:2 mixture of diaste-
reoisomers, but attempted SNAr with sodium methoxide gave 4-
nitro-N-methylaniline22 in 80% yield (Scheme 2), presumably
formed by Hoffmann elimination, rearrangement and loss of phe-
nol in the N–O bond-cleavage step.
An alternative strategy for dearylation was explored using start-
ing material 1023 N@O (Nujol) 1502 cmꢀ1] which was obtained by
[m
alkylation of phenol with 4-nitrobenzyl bromide and then reaction
with nitrosonium tetrafluoroborate.24 NDA reaction with cyclo-
hexadiene (Table 1, entry 3) and its tricarbonyliron complex (entry
4), afforded in both cases the expected cycloadduct 5 (Ar, R = H;
Ar0 = 4-(C6H4)–OCH2-4-(C6H4)NO2), though in low yields. The
structure of this product 5 was also confirmed by X-ray crystallog-
raphy (Fig. 3b), which showed the same general features as de-
scribed above in the structure of 5 (Ar, R = H; Ar0 = 4-(C6H4)NO2).
In both cases, the configuration at the nitrogen atom places the
arene nearer the CH@CH section of the hydrocarbon ring in prefer-
ence to the CH2–CH2 side.25 The cycloaddition product was
reduced with zinc in acetic acid at room temperature to give the
known 1-hydroxy-4-aminocyclohexadiene derivative which ear-
lier this year was reported26 as one of a series of products obtained
by a different route from the simple nitrosobenzene-derived cyc-
loadduct by an unusual indium triflate catalysed nucleophilic addi-
tion on the arene in a process combined with N–O bond-cleavage
in the 2-oxa-3-aza-bicyclo[2.2.2]oct-5-ene.
Table 1
Nitroso Diels–Alder reactions of cyclohexa-1,3-dienes and their tricarbonyliron
complexes (see Scheme 1)
Entry
Ar
R
Ar0
Method
Yield (%)
1
2
3
4
5
6
7
8
H
H
H
H
Ph
Ph
H
H
H
H
4-(C6H4)NO2
4-(C6H4)NO2
4-(C6H4)-Xb
4-(C6H4)-Xb
4-(C6H4)NO2
Ph
A
B
A
B
B
B
B
B
92a
58a
25a
19a
28a
68a,c
60d
82f
Me
Me
Me
(CH2)2-OAc
Ph
2-Py
Ph
e
Method A: NDA reaction using the free diene in CH2Cl2 (ꢀ78 °C to rt, 16 h); method
B: NDA reaction using the Fe(CO)3 complex in the presence of Me3NO in DMA (0 °C
to rt, 16 h).
Finally (Scheme 2), the reduction of 5 (Ar, R = H; Ar0 = 4-(C6H4)–
OCH2-4-(C6H4)NO2) was repeated under more vigorous conditions
(reflux in AcOH) to produce the deprotected phenol 12 in a single
step. Reduction of the quaternised product 11 from 4-nitro-
nitrosobenzene cycloaddition (RT in AcOH) was also examined,
giving 13 in 69% yield. Both 12 and 13 would be suitable for an
a
Regioisomer 5.
X = OCH2–C6H4NO2.
See Ref. 9.
2:1 mixture of regioisomers 6 and 5.
Ar = 3,4-(OCH2O)–C6H3.
Structure 3.
b
c
d
e
f

6808
G. R. Stephenson et al. / Tetrahedron Letters 51 (2010) 6806–6809
AgClO4, MeI
NaOMe, MeOH
H
70%
MeN
NO2
NO2
O
O
N
-
-
N
or
+
X
= BF4
-
AgBF4, MeI
48%
Me
(Ar, R = H; Ar' = 4-C6H4NO )
NO2
5
5
11
X
2
80%
1) Zn, AcOH, reflux
2) K2CO3, MeOH
OH
NO2
O
H
N
O
N
29%
(Ar, R = H; Ar' = 4-C6H4OCH2-4-C6H4NO )
2
OH
12
OH
R
N
+
OH
1) Zn, AcOH, RT
2) K2CO3, MeOH
NO2
N
O
Me
N
+
X
69%
Me
NH2
13
11
Scheme 2. Studies of N–O bond-cleavage in the 2-oxa-3-aza-bicyclo[2.2.2]oct-5-ene products (box: proposed oxidation/hydrolysis strategy for dearylation).
investigation of an oxidation/hydrolysis method to remove the aryl
group [e.g., via an iminium ion: see Scheme 2 (box)]. The reaction
sequence using the quaternised product 11 is particularly attrac-
tive because of the more efficient reduction and the early introduc-
tion of the N-methyl group that is needed in the hippeastrine
target molecule (Fig. 1a).
References and notes
1. Feature article: Yamamoto, H.; Momiyama, N. Chem. Commun. 2005, 3514–
3525; See also: Lu, P.-H.; Yang, C.-S.; Devendar, B.; Liao, C.-C. Org. Lett. 2010, 12,
2642–2645; Jones, A. L.; Snyder, J. K. Org. Lett. 2010, 12, 1592–1995; Barfoot, C.;
Brooks, G.; Davis, D. T.; Elder, J.; Giordano, I.; Hennessy, A.; Jones, G.; Markwell,
R.; McGuire, M.; Miles, T.; Pearson, N.; Spoors, G.; Sudini, R.; Wei, H.; Wood, J.
Tetrahedron Lett. 2010, 51, 2846–2848; Bollans, L.; Basca, J.; O’Farrell, D. A.;
Waterson, S.; Stachulski, A. V. Tetrahedron Lett. 2010, 51, 2160–2163; Monbaliu,
J.-C.; Tinant, B.; Peeters, D.; Marchand-Brynaert, J. Tetrahedron Lett. 2010, 51,
1052–1055; Calvert, G.; Coote, S. C.; Blanchard, N.; Kouklovsky, C. Tetrahedron
2010, 66, 2969–2980; Yan, S.; Miller, M. J.; Werner, L.; Machara, A.; Hudlicky, T.
Adv. Synth. Catal. 2010, 352, 195–200; Wencewicz, T. A.; Möllmann, U. Bioorg.
Med. Chem. Lett. 2010, 20, 1302–1305.
In conclusion, we have established that functionalised aryl ni-
troso reagents are compatible with the one-pot decomplexation–
NDA process and show the correct regiocontrol with 2-alkyl
substituted cyclohexadienes, placing the new C–N bond adjacent
to the alkyl group. The approach via the 4-nitro-nitrosobenzene
cycloaddition reaction is the most suitable and will be developed
in future work with our more fully functionalised diene complex
2 [Fig. 2; R = CH2CH2OAc, Ar = C6H3(OCH2O)], by methylation,
reduction, conversion into the exocyclic iminium ion and hydroly-
sis to remove the arene. Other key features needed for an enantio-
selective synthesis of hippeastrine by this method (the formation
of the ABC ring system7 and access to key intermediates from
enantiomerically pure arene cis-diols obtained8 using Pseudomo-
nas putida dioxygenation27) have already been established. The
work described herein now places this strategy on a firm footing
by defining the most suitable approach for the novel decomplex-
ation–NDA step.
Crystallographic data (excluding structure factors) for the struc-
tures in this Letter have been deposited with the Cambridge Crys-
tallographic Data Centre as supplementary publication nos. CCDC
786977 [5: Ar, R = H; Ar0 = 4-(C6H4)NO2] and CCDC 786978 [5: Ar,
R = H; Ar0 = 4-(C6H4)–OCH2-4-(C6H4)NO2]. Copies of the data can
be obtained, free of charge, on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK, (fax: +44-(0)1223-336033 or e-mail:
deposit@ccdc.cam.ac.uk).
2. Wichterle, O. Collect. Czech. Chem. Commun. 1947, 12, 292–304; Arbuzov, Y. A.
Dokl. Akad. Nauk SSSR 1948, 60, 993–996; Kresze, G.; Firl, I. Tetrahedron Lett.
1965, 1163–1170.
3. Anard, A.; Bhargava, G.; Kumar, V.; Mahajan, M. P. Tetrahedron Lett. 2010, 51,
2312–2315; Anand, A.; Bhargava, G.; Singh, P.; Mahajan, M. P. Heterocycles
2009, 77, 547–556; Lemos, A.; Lourcenco, J. P. Tetrahedron Lett. 2009, 50, 1311–
1313; Lam, Y.; Hopkinson, M. N.; Stanway, S. J.; Gouverneur, V. Synlett 2007,
3022–3026; Calvert, G.; Dussaussois, M.; Blanchard, N.; Kouklovsky, C. Org. Lett.
2004, 6, 2449–2451; Lightfoot, A. P.; Pritchard, R. G.; Wan, H.; Warren, J. E.;
Whiting, A. Chem. Commun. 2002, 2072–2073; Lee, J.; Chen, L.; West, A. H.;
Richter-Addo, G. B. Chem. Rev. 2002, 102, 1019–1066.
4. Zhu, L.; Lauchli, R.; Loo, M.; Shea, K. J. Org. Lett. 2007, 9, 2269–2271.
5. A recent focus on catalytic enantioselective NDA reactions has increased the
popularity of the method. See, for example: (a) Jana, C. K.; Grimme, S.; Struder,
A. Chem. Eur. J. 2009, 15, 9078–9084; (b) Momiyama, N.; Yamamoto, Y.;
Yamamoto, H. J. Am. Chem. Soc. 2007, 129, 1190–1195; (c) Jana, C. K.; Studer, A.
Angew. Chem., Int. Ed. 2007, 46, 6542–6544; (d) Yamamoto, Y.; Yamamoto, H.
Angew. Chem., Int. Ed. 2005, 44, 7082–7085; (e) Chow, C. P.; Shea, K. J. J. Am.
Chem. Soc. 2005, 127, 3678–3679; (f) Ding, X.; Ukaji, Y.; Fujinami, S.; Inomata,
K. Chem. Lett. 2003, 32, 582–583; (g) Flower, K. R.; Lightfoot, H.; Wan, H.;
Whiting, A. J. Chem. Soc., Perkin Trans. 1 2002, 2058–2064; For a review on
asymmetric NDA reactions, see: Yamamoto, Y.; Yamamoto, H. Eur. J. Org. Chem.
2006, 9, 2031–2043.
6. For other examples in target molecule synthesis, see: Sancibrao, P.; Karila, D.;
Kouklovsky, C.; Vincent, G. J. Org. Chem. 2010, 75, 4333–4336 (porantheridine);
Dunn, T. B.; Ellis, J. M.; Kofimk, C. C.; Manning, J. R.; Overman, L. E. Org. Lett.
2009, 11, 5658–5661 (daphnicyclidins); Lin, W.; Virga, K. G.; Kim, K.-H.;
Zajicek, J.; Mendel, D.; Miller, M. J. J. Org. Chem. 2009, 74, 5941–5946
(daphnipaxinin, spironoraristeromycin); Jana, C. K.; Studer, A. Chem. Eur. J.
2008, 14, 6326–6328 (trans-dihydronarciclasine); Shulka, K. H.; Boehmler, D. J.;
Bogacyzk, S.; Duvall, B. R.; Peterson, W. A.; McElroy, W. T.; DeShong, P. Org. Lett.
2006, 8, 4183–4186 (pancratistatin analogue); Hudlicky, T.; Rinner, U.;
Gonzalez, D.; Akgun, H.; Schilling, S.; Siengalewicz, P.; Martinot, T. A.; Pettit,
G. R. J. Org. Chem. 2002, 67, 8726–8743 (narciclasine); Abe, H.; Aoyagi, S.;
Kibayashi, C. J. Am. Chem. Soc. 2000, 122, 4583–4592 (fasicularine,
lepadiformine); Hall, A.; Bailey, P. D.; Rees, D. C.; Rosair, G. M.; Wightman, R.
H. J. Chem. Soc., Perkin Trans. 1 2000, 329–342 (physoperuvine, epibatidine);
Cabanal-Duvillard, I.; Berrien, J.-F.; Ghosez, L.; Husson, H.-P.; Royer, J.
Tetrahedron 2000, 56, 3763–3769 (epibatidine); Faitg, T.; Soulie, J.;
Lallemand, J.-L.; Ricard, L. Tetrahedron: Asymmetry 1999, 10, 2165–2174
(calystegine B2); Tolman, V.; Hanus, J.; Sedmera, P. Czech. Chem. Commun.
1999, 64, 696–702 (zeatin); Aoyagi, S.; Shishido, Y.; Kibayashi, C. Tetrahedron
Lett. 1991, 32, 4325–4328 (nupharamine); For a classic example to control C–N
Acknowledgements
We thank the EPSRC for financial support (Ph.D. studentships to
A.M.B. and R.D.K.) and the EPSRC National Mass Spectrometry Ser-
vice, Swansea University, for high resolution mass spectrometric
data. We thank Professor Claude Daul, University of Fribourg for
access to computational facilities.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.09.118.

G. R. Stephenson et al. / Tetrahedron Letters 51 (2010) 6806–6809
6809
bond formation in alkaloid synthesis, see: Iida, H.; Watanabe, Y.; Kibayashi, C. J.
Org. Chem. 1985, 50, 1818–1825.
7. Astley, S. T.; Stephenson, G. R. Synlett 1992, 507–509.
8. Astley, S. T.; Meyer, M.; Stephenson, G. R. Tetrahedron Lett. 1993, 34, 2035–
2038.
Miller, M. J.; Zajicek, J.; Noll, B. C.; Möllmann, U.; Dahse, H.-M.; Miller, P. A. Org.
Lett. 2007, 9, 2923–2926) including polymer-supported examples: Krchnak, V.;
Möllmann, U.; Dahse, H.-M.; Miller, M. J. J. Comb. Chem. 2008, 10, 112–117. This
has provided many examples of high-yielding NDA reactions with this class of
heterodienophile.
9. Anson, C. E.; Hartman, S.; Kelsey, R. D.; Stephenson, G. R. Polyhedron 2000, 19,
569–571.
10. The acylnitroso class of heterodienophiles does not naturally give this
regioselectivity (see Ref. 13), but Shea’s approach overcomes this difficulty
by using an intramolecular cycloaddition strategy.
15. Yamamoto, Y.; Yamamoto, H. J. Am. Chem. Soc. 2004, 126, 4128–4129.
16. The reported regioselectivity may be a consequence of the Cu(I)-catalysis (see
Refs. 14,5a) which is not compatible with the use of trimethylamine N-oxide in
the tandem decomplexation/NDA procedure.
17. Møller, E.; Jørgensen, K. A. J. Org. Chem. 1996, 61, 5770–5778.
18. See also: Zhao, D.; Johansson, M.; Backvall, J.-E. Eur. J. Org. Chem. 2007, 4431–
4436.
19. Defoin, A.; Geoffroy, G.; le Nouen, D.; Spileers, D.; Streith, J. Helv. Chim. Acta
1989, 72, 1199–1215; For recent examples of the use of this nitroso reagent,
see: (a) Tibiletti, F.; Simonetti, M.; Nicholas, K. M.; Palmisano, G.; Parravicini,
M.; Imbesi, F.; Tollari, S.; Penoni, A. Tetrahedron 2010, 66, 1280–1288; (b) Rück-
Braum, K.; Kempa, S.; Priewisch, B.; Richter, A.; Seedorff, S.; Wallach, L.
Synthesis 2009, 4256–4267; (c) Sakai, H.; Ding, X.; Yoshida, T.; Fujinami, S.;
Ukaji, Y.; Inamata, K. Heterocycles 2008, 76, 1285–1300.
11. For other recent examples of tricarbonyliron complexes in organic synthesis,
see: Pearson, A. J.; Kim, E. H. Tetrahedron 2010, 66, 4943–4946; Han, J.-L.; Liu,
M.-C.; Ong, C.-W. J. Org. Chem. 2010, 75, 1637–1642; Roe, C.; Sandoe, E. J.;
Stephenson, G. R. Tetrahedron Lett. 2010, 51, 591–595; Gone, J. R.; Wallock, N.
J.; Lindeman, S.; Donaldson, W. A. Tetrahedron Lett. 2009, 50, 1023–1025; Knott,
K. E.; Auschill, S.; Jäger, A.; Knölker, H.-J. Chem. Commun. 2009, 1467–1469;
Anson, C. E.; Malkov, A. V.; Roe, C.; Sandoe, E. J.; Stephenson, G. R. Eur. J. Org.
Chem. 2008, 196–213; Roe, C.; Sandoe, E. J.; Stephenson, G. R.; Anson, C. E.
Tetrahedron Lett. 2008, 49, 650–653; Roe, C.; Stephenson, G. R. Org. Lett. 2008,
10, 189–192; Pearson, A. J.; Sun, H. J. Org. Chem. 2007, 72, 7693–7700;
Williams, I.; Reeves, K.; Kariuki, B. M.; Cox, L. Org. Biomol. Chem. 2007, 5, 3325–
3329; Pearson, A. J.; Sun, H.; Wang, X. J. Org. Chem. 2007, 72, 2547–2557; Owen,
D. A.; Malkov, A. V.; Palotai, I. M.; Roe, C.; Sandoe, E. J.; Stephenson, G. R. Chem.
Eur. J. 2007, 13, 4293–4311; Siddiquee, T. A.; Lukesh, J. M.; Lindeman, S.;
Donaldson, W. A. J. Org. Chem. 2007, 72, 9802–9803; Pandey, R. K.; Lindeman,
S.; Donaldson, W. A. Eur. J. Org. Chem. 2007, 3829–3831; Choi, T. A.; Czerwonka,
R.; Fröhner, W.; Krahl, M. P.; Reddy, K. R.; Franzzblau, S. G.; Knölker, H.-J.
ChemMedChem 2006, 1, 812–815; Czerwonka, R.; Reddy, K. R.; Baum, E.;
Knölker, H.-J. Chem. Commun. 2006, 711–713; Chaudhury, S.; Danoaldson, W.
A. J. Am. Chem. Soc. 2006, 128, 5984–5985; Pearson, A. J.; Wang, X. Tetrahedron
Lett. 2005, 46, 4809–4811; Frank-Neumann, M.; Geoffrey, P.; Gassmann, D.;
Winling, A. Tetrahedron Lett. 2004, 45, 5407–5410; Schobert, R.; Mangold, A.;
Baumann, T.; Milius, W.; Hampel, F. J. Organomet. Chem. 2004, 689, 575–584;
Stephenson, G. R. Polyfunctional Electrophilic Multihapto-organometallics for
Organic Synthesis. In Handbook of Functionalised Organometallics; Knochel, P.,
Ed.; Wiley-VCH: Weinheim, 2005; pp 569–626 (ISBN 3-527-31131-9).
12. Tandem decomplexation/NDA is important because of the sensitive (see Ref. 9)
lactone ring in this diene ligand (see Fig. 1a).
20. Davey, M. H.; Lee, Y. V.; Miller, R. D.; Marks, T. J. J. Org. Chem. 1999, 64, 4976–
4979.
21. Møller’s study (Ref. 17; 1996) also performed semiempirical AM1 calculations
to identify the orientation of the aryl group. Our 2000 (Ref. 9) example and the
two examples reported in this Letter show similar orientations of the aryl
group in the solid state and support the earlier conclusions based on
calculations. For a crystallographically defined pyridyl example, see Ref. 15.
See also Ref. 25.
22. Katritzky, A.; Lourenzo, K. S. J. Org. Chem. 1988, 53, 3978–3982.
23. Attempts to nitrosylate the benzyl ether of phenol were unsuccessful, so we
examined nitrobenzyl ether in the expectation that this would deactivate the
benzyl arene and so improve selectivity for the phenyl ether ring.
24. The corresponding nitrosylations of anisole and 4-nitrophenyl phenyl ether are
known: Atherton, J. H.; Modie, R. B.; Noble, D. R.; O’Sulivan, B. J. Chem. Soc.,
Perkin Trans. 2 1997, 663–664; See also Ref. 19a.
*
25. Preliminary DFT calculations (GAUSSIAN03/B3LYP/6-31 g ) indicate that the more
stable orientation has the arene lying over the CH@CH section of the
hydrocarbon ring in preference to the CH2–CH2 side [energy differences with
Ar = Ph: ꢀ0.0839497 Ha (220 kJ molꢀ1); Ar = 4-NO2–C6H4: ꢀ0.0033301 Ha
(8.7 kJ molꢀ1) in the gas phase].
13. Howard, J. A. K.; Ilyashenko, G.; Sparkes, H. A.; Whiting, A.; Wright, A. R. Adv.
Synth. Catal. 2008, 350, 869–882; Howard, J. A. K.; Ilyashenko, G.; Sparkes, H.
A.; Whiting, A. J. Chem. Soc., Dalton Trans. 2007, 2108–2111; Adamo, M. F. A.;
Bruschi, S. Targets Heterocycl. Syst. 2007, 11, 396–430.
14. There has been considerable recent interest in applications of 2-
nitrosopyridine reagents in MEND (Modular Enhancement of Nature’s
Diversity) procedures (Yang, B.; Zöllner, T.; Gebhard, P.; Möllmann, U.;
Miller, M. J. Org. Biomol. Chem. 2010, 8, 691–697; Yang, B.; Miller, P. A.;
Möllmann, U.; Miller, M. J. Org. Lett. 2009, 11, 2828–2831; Li, F.; Yang, B.;
26. Yang, B.; Miller, M. J. Org. Lett. 2010, 12, 392–395.
27. For a recent review, see: Hudlicky, T.; Reed, J. T. Synlett 2009, 685–703; for cis-
diol-derived dieneiron complexes, see: Howard, P. W.; Stephenson, G. R.;
Taylor, S. C. J. Organomet. Chem. 1989, 370, 97–109; Howard, P. W.; Stephenson,
G. R.; Taylor, S. C. J. Organomet. Chem. 1988, 339, C5–C8; related example
(monool): Howard, P. W.; Stephenson, G. R.; Taylor, S. C. Chem. Commun. 1990,
1182–1184.