Exploration of Nicholas methodology using chiral heterobimetallic cobalt-molybdenum propargylium complexes

Article abstract of DOI:10.1016/S0040-4039(02)01670-2

Nicholas methodology has been used successfully with chiral heterobimetallic cobalt-molybdenum propargylium complexes in the formation of enyne complexes, new stereocentres and heteroatom ring systems, in high yield and moderate diastereoselectivity.

Full text of DOI:10.1016/S0040-4039(02)01670-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 7167–7170
Exploration of Nicholas methodology using chiral
heterobimetallic cobalt–molybdenum propargylium complexes
Steven D. R. Christie,* Ryan J. Davoile and Raymond C. F. Jones*
Department of Chemistry, University of Loughborough, Loughborough LE11 3TU, UK
Received 19 July 2002; accepted 9 August 2002
Abstract—Nicholas methodology has been used successfully with chiral heterobimetallic cobalt–molybdenum propargylium
complexes in the formation of enyne complexes, new stereocentres and heteroatom ring systems, in high yield and moderate
diastereoselectivity. © 2002 Elsevier Science Ltd. All rights reserved.
The use of dicobalt hexacarbonyl propargylium com-
plexes in the Nicholas reaction, which involves addi-
tion of nucleophiles to complexed propargylic cations,
The Co–Mo alkyne aldehyde complex 3 was first pre-
pared by complexation of but-2-ynal diethyl acetal 1
(Co (CO) , DCM, 25°C) to afford 2 (Scheme 1).
1
2
8
is a widely known and explored method of CꢀC and
Isolobal displacement of Co(CO)3 with MoCp(CO)2
2
Cꢀheteroatom bond formation. This chemistry has
using the molybdenum anion [Mo(CO) ]K (THF reflux,
3
been developed with the use of dimolybdenum dicy-
clopentadienyl tetracarbonyl and diastereomeric
2
h) and hydrolysis of the diethyl acetal on chromato-
graphic purification led to 3 (86% from uncomplexed
3,4
dicobalt pentacarbonyl arylphosphite complexes, the
latter establishing a route to enantiomerically enriched
acetal 1).
5
diastereomeric product complexes. Application to the
Grignard reagent addition to the heterobimetallic alde-
hyde complex 3 at −78°C in THF, as we have previ-
ously reported, led to the propargylic alcohols 4a–e in
synthesis of ether ring systems has been recognised as a
6
–10
key step in natural product synthesis.
18
9
3–96% yield and 5:1 to 10:1 d.r. Slow addition of
Although a great deal of research has been carried out
with homobimetallic systems, limited chemistry has
been carried out with heterobimetallic propargylium
complexes. Examples of interest are the inherently chi-
ral complexes of cobaltmolybdenum cyclopentadienyl
pentacarbonyl propargylium complex alkyne[Co-
HBF to these alcohols (Et O, 25°C) gave the orange,
4
2
air stable propargylic salt complexes 5a–e, respectively,
19
in 81–93% yield (Scheme 2).
MoCp(CO) ], where synthesis and characterisation are
5
known in the literature, but only limited reactivity
1
1–17
studies have been reported.
With these precedents in mind, we report herein our
exploration of the chiral directing capability of the
heterobimetallic Co–Mo–alkyne core in nucleophilic
attack via the Nicholas approach using propargylic salt
complexes both preformed, and formed in situ after
protonation of the corresponding enyne. We have also
used this methodology in intramolecular nucleophilic
additions to form heterocycles. Yields are high, and
moderate stereoselectivity is observed.
*
Corresponding authors. Tel.: +44-1509-222587, 222557; fax: +44-
509-223926; e-mail: s.d.christie@lboro.ac.uk; r.c.f.jones@lboro.
ac.uk
1
Scheme 1.
0
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01670-2

7
168
S. D. R. Christie et al. / Tetrahedron Letters 43 (2002) 7167–7170
As the highest diastereoselectivity was found with the
isobutyl substrate 5e, additions with different het-
eroatom nucleophiles were carried out using this salt
(
Scheme 4). Excellent yields of 6a–c were achieved;
diastereoselectivity was moderate but improved at
40°C relative to room temperature (Table 1, entries
−
6
20
–11). The diastereoisomers were not separable by
standard column chromatography, and all products
formed were oils, hence diastereoselectivities were con-
1
firmed using 250 MHz H NMR spectroscopy.
When the propargylic salt complexes 5a–e were treated
with the mild base N-ethyldiisopropylamine (H u¨ nig’s
base) (MeCN, 25°C), the corresponding trans enynes
2
2,23
7
a–e were obtained in 83–94% yield (Scheme 5).
Scheme 2.
Nucleophilic addition to the propargylic salts 5 was
examined using water over a range of solvents and
temperatures. Optimum conditions were found to be in
MeCN at −40°C (Scheme 3). Interestingly, the relative
d.r. of the returned alcohol complexes 4a–e (Table 1,
entries 1–5) was reversed compared to those isolated
from the Grignard addition reaction (Scheme 2), thus
enabling access to both alcohol diastereoisomers, which
are separable by column chromatography. In the case
of benzyl substituted cation 5d, the corresponding
alkene 7d (see below) was isolated.
Scheme 4.
Scheme 3.
Scheme 5.
Table 1. Nucleophilic capture of propargylic salt complexes 5 and alkene complexes 7
Entry
Complex
Product
Nucleophile
T (°C)
Yield (%)
D.r.
1
2
3
4
5
5a
5b
5c
5d
5e
4a
4b
4c
(4d)
4e
H O
−40
−40
−40
−40
−40
68
62
64
78
70
1:3
1:5
1:4.5
2
H O
2
H O
2
H O
(Alkene 7d isolated)
1:6
2
H O
2
6
7
5e
5e
5e
6a
6b
6c
4-Nitrophenol
PhSH
25
−40
58
89
1:1.5
1:2
8
9
25
−40
90
93
1:2
1:4
10
11
12
13
14
15
16
1,2,3-Benzotriazole
25
−40
25
25
25
91
95
59
61
66
30
65
1:1
1:3
1:2
1:3
1:5
1:1
1:5
7a
7b
7c
7d
7e
4a
4b
4c
4d
4e
H O
2
H O
2
H O
2
H O
25
25
2
H O
2

S. D. R. Christie et al. / Tetrahedron Letters 43 (2002) 7167–7170
7169
1
As only 7b showed any sign of a cis enyne by H NMR
spectroscopy, this indicated that more highly substi-
tuted R-groups favour trans enyne formation. This
useful preparation of the enyne complexes bypasses the
21
enynes themselves, and may be valuable in synthesis.
We wished to determine whether addition of a nucle-
ophile to the propargylic carbon atom of the alkenes 7
would be possible and would give results matching
direct addition to the salt complexes 5. Complexes 7a–e
were thus treated successively with HBF4 (MeCN,
2
5°C), water and H u¨ nig’s base (Scheme 5). Alcohol
complexes 4a–e were indeed recovered (Table 1, entries
2–16); yields were lower than direct addition of water
1
to the salt complexes 5, with recovery of 10–40% of
alkene. The alcohol complexes 4 had equivalent or
lower d.r. than from direct addition to the salt com-
plexes and in the same direction (Table 1). It is thus
likely that the reactions proceed via the same transition
state. Benzyl substituted alcohol 4d was retrieved in
only 30% yield from a mixture; non-regiospecific proto-
nation and stability (conjugation) of alkene 7d may be
factors here.
Scheme 7.
with BF ·OEt (DCM, −78°C) in 20% yield (unopti-
3
2
mised) and d.r 1:2.
To conclude, preliminary studies using Nicholas
methodology with inherently chiral heterobimetallic
Co–Mo propargylium complexes have demonstrated
the generation of new propargylic centres by nucle-
ophilic addition in high yields with moderate to good
stereoselectivity, and of enyne complexes. Intramolecu-
lar nucleophilic capture to form heterocycles shows
promise and development is continuing in this area,
including extension to nitrogen heterocycles.
We wished to demonstrate the scope of this methodol-
ogy for assembly of diastereomerically enriched hetero-
cyclic rings of varying size via intramolecular
nucleophile capture. Thus, we first prepared simple
substrate 8 from 3-bromo-1-propanol by protection as
the tert-butyl ether (2-methylpropene, Amberlyst, hex-
2
4
ane), generation of the Grignard reagent (Mg, cat.
,2-bromoethane, THF reflux) and addition to the alde-
hyde complex 3 in good yield and d.r. (89%, 7:1)
Scheme 6). Initial trials with THP and tert-
1
Acknowledgements
We thank the EPSRC for a studentship (R.J.D).
References
(
butyldimethylsilyl protecting groups were unsuccessful.
A series of Lewis acids was examined for deprotection–
ring closure. TFA, TiCl4 and HBF4 all formed the
corresponding alkene by water loss, but on reaction
with BF ·OEt (DCM, −78°C) the tetrahydrofuran 9
was isolated (79%) with reduced d.r. (2:1), as observed
by H NMR spectroscopy.
3
2
1
2
3
. Nicholas, K. M.; Pettit, R. Tetrahedron Lett. 1971, 12,
474–3477.
. Schegolev, A. A.; Smit, W. A. Tetrahedron Lett. 1982, 23,
419–4422.
. Curtis, M. D. Tetrahedron 1987, 6, 759–782.
1
25
3
As a pilot study of six-ring formation, we decided to
4
make the unsubstituted dihydrobenzopyran 12 (Scheme
7
). Bromination of the primary alcohol of 10 (PBr , cat.
3
4. Nicholas, K. M.; Bradley, D. H.; Khan, M. A.
HBr, AcOH; 49%) was followed by protection of the
phenol as its tert-butyl ether as above (54%), genera-
tion of the Grignard reagent and subsequent addition
to 3 to furnish complex 11 in 75% yield and d.r. 7:1.
The cyclisation product 12 was formed on treatment
Organometallics 1992, 11, 2598–2607.
5
. Nicholas, K. M.; Caffyn, A. J. M. J. Am. Chem. Soc.
993, 115, 6438–6439.
. Isobe, M.; Tanaka, S. Tetrahedron 1994, 50, 5633–5644.
1
6
7. Isobe, M.; Tsuboi, K.; Ichikawa, Y.; Jiang, Y.;
Naganawa, A. Tetrahedron 1997, 53, 5123–5142.
8
. Isobe, M.; Liu, T.; Li, J. Tetrahedron 2000, 56, 10209–
0219.
1
9. Hanaoka, M.; Mukai, C.; Sugimoto, Y.; Miyazawa, K.;
Yamaguchi, S. J. Org. Chem. 1998, 63, 6281–6287.
1
1
1
1
0. Mukai, C.; Yamashita, H.; Sassa, M.; Hanaoka, M.
Tetrahedron 2002, 58, 2755–2762.
1. McGlinchey, M. J.; D’Agostino, M. F.; Frampton, C. S.
Organometallics 1990, 9, 2972–2984.
2. Song, L.; Shen, J.; Hu, Q.; Han, B.; Wang, R.; Wang, H.
Inorg. Chim. Acta 1994, 219, 93–97.
3. Hong, F.; Lue, I.; Lo, S.; Lin, C. J. Organomet. Chem.
1995, 495, 97–101.
Scheme 6.

7
170
S. D. R. Christie et al. / Tetrahedron Letters 43 (2002) 7167–7170
1
4. Gruselle, M.; McGlinchey, M. J.; Kondratenko, M.; El
Hafa, H.; Vaissermann, J.; Jaouen, G. J. Am. Chem. Soc.
995, 117, 6907–6913.
21. See, for example: Caddick, S.; Delisser, V. M. Tetra-
hedron Lett. 1997, 38, 2355–2358; Melikyan, G. G.;
Khan, M. A.; Nicholas, K. M. Organometallics 1995, 14,
2170–2172.
1
1
1
1
1
1
5. Gruselle, M.; Kondratenko, M.; El Amouri, H.; Vaisser-
mann, J. Organometallics 1995, 14, 5242–5250.
22. Cf in Co–Co system: Nicholas, R. M.; Pettit, R. J.
Organomet. Chem. 1972, 44, C21–C24.
6. Gruselle, M.; Mal e´ zieux, B.; Vaissermann, J.; Amouri, H.
Organometallics 1998, 17, 2337–2343.
7. Christie, S. D. R.; Fletcher, A. J.; Rutherford, D. T.
23. Enyne complex 7e. To Co–Mo salt complex 5e (100 mg,
0.18 mmol) in dry acetonitrile (10 mL) stirred under
Synlett 2000, 1040–1042.
nitrogen at 25°C was added H u¨ nigs base (0.05 mL, 0.36
mmol). The reaction mixture was stirred for 30 min
before filtration through a pad of Celite and silica. The
solvent was removed in vacuo to leave a red oil, purified
by flash silica chromatography eluting with light
petroleum:diethyl ether (15:1 v/v) to yield the enyne
8. Christie, S. D. R.; Fletcher, A. J.; Fryatt, R.; Rutherford,
D. T.; Elsegood, M. R. J. Synlett 2001, 1711–1714.
9. Typical procedure: salt complex 5e. To cobalt molybde-
num alcohol complex 4e (1.50 g, 3.10 mmol) in dry
diethyl ether (40 mL) stirred under nitrogen was added
dropwise tetrafluoroboric acid (54 wt.%; 0.60 mL, 4.30
mmol). The reaction mixture was stirred for a further 10
min before the precipitated orange solid was filtered,
washed with dry diethyl ether (60 mL) and dried under
reduced pressure to yield the salt 5e as an orange solid
−
1
complex 7e as a red oil (72 mg, 86%). IR (film)/cm
1
2
959, 2045, 1968, 1885. H NMR (250 MHz, CDCl ) 6.34
3
(
1H, d, J=15 Hz), 5.67 (1H, dd, J=7, 22 Hz), 5.33 (5H,
s), 2.65 (3H, s), 2.47–2.34 (1H, m), 1.03 (6H, d, J=6 Hz).
1
3
−
1
C NMR (100 MHz, CDCl ) 226.3, 225.5, 203.9, 141.8,
(
1.59 g, 93%). IR (KBr)/cm 2045, 1974, 1932. mp=
3
+
1
26.2, 91.1, 90.0, 31.5, 22.7, 22.6, 21.4. Found: M ,
8
7–88°C (dec.). Found: C, 38.43; H, 3.21%. C H O −
18 18 5
4
69.9462. C H O CoMo requires 469.9462.
BCoF Mo requires C, 38.88; H, 3.26%.
18 17
5
4
2
0. Typical procedure: complex 6b. To Co–Mo salt complex
e (435 mg, 0.78 mmol) in dry acetonitrile (20 mL)
stirred under nitrogen at −40°C was added thiophenol
0.12 mL, 1.17 mmol). The reaction mixture was stirred
for 30 min at −40°C, before addition of H u¨ nigs base
0.20 mL, 1.56 mmol). The reaction mixture was allowed
24. Alexakis, A.; Gardette, M.; Colin, S. Tetrahedron Lett.
1988, 29, 2951–2954.
5
25. Tetrahydrofuran complex 9. To Co–Mo complex 8 (200
mg, 0.37 mmol) in dry DCM (15 mL) stirred under
nitrogen at −78°C was added BF ·OEt (0.14 mL, 1.11
(
3
2
(
mmol). The reaction mixture was stirred for 30 min and
to warm to 25°C before filtration through a pad of
Celite and silica. The solvent was removed in vacuo to
leave a red oil, purified by flash silica chromatography
eluting with light petroleum:diethyl ether (10:1 v/v) to
yield the complex 6b as a red oil (420 mg, 93%, 1:4
H O (0.2 mL) was added before filtration through a pad
2
of Celite and silica, washing with DCM and EtOH. The
solvents were removed in vacuo to leave a red oil,
purified by flash silica chromatography eluting with light
petroleum:diethyl ether (10:1 v/v) to yield the tetra-
hydrofuran 9 as a red oil (136 mg, 79%, 2:1 mixture of
−
1
mixture of diastereoisomers). IR (film)/cm 2044, 1970,
1
1
933. Major diastereoisomer: H NMR (250 MHz,
−1
diastereoisomers). IR (film)/cm 2044, 1969, 1926. Major
CDCl ) 7.41–7.20 (5H, m), 5.20 (5H, s), 4.50–4.40 (1H,
1
3
diastereoisomer: H NMR (250 MHz, CDCl ) 5.44 (5H,
3
m), 2.69 (3H, s), 2.09–1.92 (1H, m), 1.72–1.56 (2H, m),
s), 4.82 (1H, t, J=7 Hz), 3.94–3.75 (2H, m), 2.68 (3H, s),
1
3
0
2
9
.92 (6H, dd, J=2, 7 Hz). C NMR (100 MHz, CDCl3)
2
.24–2.11 (1H, m), 2.02–1.87 (2H, m), 1.71–1.57 (1H, m).
26.9, 225.1, 204.8, 138.1, 130.4, 129.4, 126.7, 100.8,
2.6, 90.9, 55.2, 48.5, 26.5, 23.6, 22.1, 21.5. Minor
diastereoisomer: H NMR (250 MHz, CDCl ) 7.41–7.20
1
3
C NMR (100 MHz, CDCl ) 226.6, 224.9, 204.4, 98.4,
3
1
91.2, 90.2, 83.0, 67.9, 34.0, 26.7, 20.1. Minor diastereoiso-
3
1
mer: H NMR (250 MHz, CDCl ) 5.41 (5H, s), 4.98 (1H,
3
(
2
5H, m), 5.40 (5H, s), 4.50–4.40 (1H, m), 2.56 (3H, s),
13
t, 7 Hz), 3.94–3.75 (2H, m), 2.70 (3H, s), 2.24–2.11 (1H,
.09–1.92 (1H, m), 1.72–1.56 (2H, m), 0.89 (6H, m).
C
13
m), 2.02–1.87 (2H, m), 1.71–1.57 (1H, m). C NMR (100
NMR (100 MHz, CDCl ) 227.1, 225.0, 204.8, 137.8,
3
MHz, CDCl ) 226.0, 225.2, 204.4, 98.5, 91.8, 90.2, 83.1,
1
2
30.8, 129.5, 126.8, 101.7, 93.7, 90.9, 54.6, 48.9, 26.2,
3.8, 21.9, 21.4. Found: M −3CO, 495.98165.
3
+
+
68.0, 33.2, 26.6, 20.6. Found: M −CO, 443.93075.
C H O CoMoS requires 495.98070.
C H O CoMo requires 443.93055.
16 15 5
21
23
2