Organolanthanide-Catalyzed Cyclization/Boration of 1,5- and 1,6-Dienes

Article abstract of DOI:10.1021/ol006841s

(Matrix Presented) 1,5- and 1,6-Dienes undergo a cyclization/boration reaction in the presence of a catalytic amount of Cp*₂Sm·THF. The resulting organoboranes can be oxidized to the corresponding primary cyclic alcohols using standard conditions.

Full text of DOI:10.1021/ol006841s

ORGANIC
LETTERS
2001
Vol. 3, No. 3
361-363
Organolanthanide-Catalyzed Cyclization/
Boration of 1,5- and 1,6-Dienes
Gary A. Molander* and Dirk Pfeiffer
Roy and Diana Vagelos Laboratories, Department of Chemistry,
UniVersity of PennsylVania, Philadelphia, PennsylVania 19104-6323
gmolandr@sas.upenn.edu
Received November 8, 2000
ABSTRACT
1,5- and 1,6-Dienes undergo a cyclization/boration reaction in the presence of a catalytic amount of Cp*2Sm‚THF. The resulting organoboranes
can be oxidized to the corresponding primary cyclic alcohols using standard conditions.
Group 3 and lanthanide metallocenes have been extensively
investigated as catalysts promoting highly stereoselective
cyclization/silylation reactions of monosubstituted and 1,1-
disubstituted 1,5- and 1,6-dienes to functionalized car-
bocycles.1 However, the synthetic utility of the organolan-
thanide-promoted cyclization/silylation reaction suffers from
the fact that in some cases conversion of the organosilanes
to the corresponding alcohols proved to be difficult.2
Furthermore, synthetically useful transformations of alkyl-
silanes are relatively limited. Although carbon-carbon bond
forming reactions via Pd(0)-catalyzed cross-coupling events
have been realized, these transformations generally require
activation of the organosilane by fluoride.3 It was not obvious
that the types of organosilanes generated by our cyclization/
silylation protocol would be conducive to this transformation.
To address these limitations, alternative reagents need to be
developed to trap the cyclized organometallic intermediate
leading to products that can be functionalized under mild
conditions.
The use of organoboranes in organic synthesis is well
established,4 and a termination reaction involving a suitable
boration reagent would create products open to the full palette
of organoboron chemistry. Encouragingly, hydroboration
reactions catalyzed by lanthanide metallocenes have been
previously reported.5 The resultant organoboranes were
oxidized to the corresponding alcohols using basic hydrogen
peroxide. However, the only reported cyclization reactions
involving boranes were addition-carbocyclization protocols
of enynes and diynes catalyzed by transition metals with
compounds containing interheteroatom bonds such as B-Sn
or B-Si.6 In this contribution we report the first metal-
catalyzed cyclization/boration reaction.
(1) (a) Molander, G. A. Chemtracts 1998, 11, 237 and references therein.
(b) Molander, G. A.; Dowdy, E. D.; Schumann, H. J. Org. Chem. 1998,
63, 3386. (c) Molander, G. A.; Nichols, P. J.; Noll, B. C. J. Org. Chem.
1998, 63, 2292. (d) Molander, G. A.; Nichols, P. J. J. Org. Chem. 1996,
61, 6040. (e) Molander, G. A.; Nichols, P. J. J. Am. Chem. Soc. 1995, 117,
4415. (f) Onozawa, S.; Sakakura, T.; Tanaka, M. Tetrahedron Lett. 1994,
35, 8177. (g) Molander, G. A.; Dowdy, E. D. In Topics in Organometallic
Chemistry; Kobayashi, S., Ed.; Springer-Verlag: New York, 1999; Vol. 2,
pp 120-154.
(2) Molander, G. A.; Corette, C. P. J. Org. Chem. 1999, 64, 9697.
(3) (a) Mowery, W. E.; DeShong, P. J. Org. Chem. 1999, 64, 1884. (b)
Matsuhashi, H.; Asai, S.; Hirabayashi, K.; Hatanaka, Y.; Mori, A.; Hiyama,
T. Bull. Chem. Soc. Jpn. 1997, 70, 437. (c) Hiyama, T.; Hatanaka, Y. Pure
Appl. Chem. 1994, 66, 1471. (d) Matsuhashi, H.; Kurobashi, M.; Hatanaka,
Y.; Hiyama, T. Tetrahedron Lett. 1994, 35, 6507. (e) Hatanaka, Y.; Hiyama,
T. Tetrahedron Lett. 1990, 31, 2719. (f) Hatanaka, Y.; Hiyama, T. J. Am.
Chem. Soc. 1990, 112, 7793.
The proposed catalytic cycle of the organolanthanide-
catalyzed cyclization/boration reaction is outlined in Scheme
(4) Brown, H. C. Organic Syntheses Via Boranes; Wiley-Interscience:
New York, 1975. Reprinted Edition, Vol. 1; Aldrich Chemical Co. Inc.:
Milwaukee, WI, 1997; Chapter 9.
(5) (a) Harrison, K. N.; Marks, T. J. J. Am. Chem. Soc. 1992, 114, 9220.
(b) Bijpost, E. A.; Duchateau, R.; Teuben, J. H. J. Mol. Catal. 1995, 95,
121.
(6) (a) Onozawa, S.; Hatanaka, N. C.; Choi, N.; Tanaka, M. Organo-
metallics 1997, 16, 5389 and references therein. (b) Onozawa, S.; Hatanaka,
Y.; Tanaka, M. J. Chem. Soc., Chem. Commun. 1997, 1229.
10.1021/ol006841s CCC: $20.00 © 2001 American Chemical Society
Published on Web 01/10/2001

Scheme 1a
Table 1. Optimization of the Organolanthanide Catalyzed
Cyclization/Boration Reaction of 1,5-Hexadiene (1)a
a Cp′ ) Cp* (Pentamethylcyclopentadienyl) or CpTMS (Trimeth-
ylsilylcyclopentadienyl).
1. Most individual steps of the transformation are well
precedented.5 The precatalyst reacts with the organoborane
via σ-bond metathesis to generate the catalytically active
organolanthanide hydride species “Cp′2LnH” (Cp′ ) Cp*
pentamethylcyclopentadienyl or CpTMS trimethylsilylcyclo-
pentadienyl). Next, the catalyst “Cp′2LnH” regioselectively
inserts into the least hindered olefin, placing the metal with
its bulky ligands at the terminus of the carbon chain. As
depicted in Scheme 1, the resulting hydrocarbyl undergoes
an intramolecular insertion into the second olefin through a
chairlike transition structure. Finally, σ-bond metathesis
produces the desired organoborane and regenerates the
catalyst to complete the catalytic cycle.
In an attempt to build on the initial study by Marks and
co-workers,5 the conditions of the original lanthanide-
catalyzed hydroboration reaction using catecholborane and
Cp*2Sm‚THF as the precatalyst were applied to attempt the
cyclization/boration reaction of 1,5-hexadiene (1) (Table 1,
eq 1).7 However, examination of the reaction mixture after
18 h by 11B NMR spectroscopy showed no evidence of a
hydroboration reaction (entry a). An additional peak at δ
a In entries a-d, all reactions were monitored by 11B NMR spectroscopy.
Compound 6 was isolated using the procedure in ref 7. In entry b, byproducts
hex-5-ene-1-ol and 1,6-hexanediol were identified by GC-co-injection of
commercial samples.
12.12 ppm in the 11B NMR spectrum of the reaction mixture
indicated partial decomposition of the catecholborane to
different borane species.
Next, pinacolborane was examined as a boration reagent
in combination with different precatalysts (entry b). All of
the hydroboration reactions went to completion after 18 h
as evidenced by 11B NMR spectroscopy. Unfortunately, the
desired cyclized product cyclopentylmethanol (6) could only
be isolated in yields up to 50%. Other byproducts, such as
hex-5-ene-1-ol and 1,6-hexanediol, were identified.
Apparently, after the initial insertion of the catalyst into
the olefin, σ-bond metathesis of the hydrocarbyl efficiently
competes with the cyclization event to afford uncyclized
organoboranes.
(7) Representative Procedure for Lanthanide Catalyzed Cyclization/
Boration (Table 1; Entry c, R ) Me). In a nitrogen filled glovebox, the
precatalyst (0.010 g, 1.6 mol %) was dissolved in 3 mL of toluene. After
the addition of 1,5-hexadiene (1) (0.10 g, 1.22 mmol) the resultant reaction
mixture was stirred for 10 min at ambient temperature, during which time
the color of the solution changed from brown/purple to red. Next, freshly
distilled 1,3-dimethyl-1,3-diaza-2-boracyclopentane (0.164 g, 1.30 mmol)
was added dropwise over a period of 10 min. After stirring for 18 h the
reaction was found to be complete as evidenced by 11B NMR spectroscopy.
The solvent was removed in a vacuum. Next, 3 mL of 3M NaOH, 3 mL of
THF, and 3 mL of 30% H2O2 were added, and the mixture was stirred for
18 h. The resulting suspension was saturated with K2CO3, followed by
extraction with 4 × 20 mL of ether. The organic layers were combined,
washed with 15 mL of saturated NH4OH, and dried over Na2SO4. After
removal of the solvent in a vacuum, purification by flash chromatography,
followed by Kugelrohr distillation, afforded 6 (Rf 0.16 in hexane/EtOAc
10:1) in 86% yield (0.104 g, 1.04 mmol). The compound was identified by
comparison of the spectral and analytical data with commercial samples
(see also Supporting Information).
To slow σ-bond metathesis and hence promote the
cyclization reaction, 1,3-diaza-2-boracycloalkanes were ex-
amined (entry c).8 Only 1,3-dimethyl-1,3-diaza-2-boracy-
clopentane proved to be an efficient boration reagent,
affording 6 in 86% yield. The cyclization/boration reaction
with 1,3-diethyl-1,3-diaza-2-boracyclopentane provided 6 in
only 45% yield. Examination of the reaction mixture by 11
B
NMR spectroscopy after 18 h showed a significant amount
of unreacted 1,3-diethyl-1,3-diaza-2-boracyclopentane. 1,3-
(8) Merriam, J. S.; Niedenzu, K. Inorg. Synth. 1972, 44, 162.
Org. Lett., Vol. 3, No. 3, 2001
362

Diisopropyl-1,3-diaza-2-boracyclopentane showed no evi-
dence of a hydroboration reaction. The increased steric bulk
on the nitrogen apparently slows down the σ-bond metathesis
between the hydrocarbyl and the 1,3-diaza-2-boracycloal-
kanes to the point where no reaction occurs.
protocol. According to Marks, the divalent samarium pre-
catalyst converts to a trivalent active organosamarium species
by allylic C-H activation.11 The initial allylmetallic inter-
mediate, where R ) OTBDPS, could perform irreversible
reactions with the protected alcohol functional group that
are perhaps responsible for this result.
The moisture sensitive borane resulting from boration/
cyclization of 1 was isolated from the reaction mixture via
distillation under inert atmosphere. This borane was con-
verted to the air stable potassium trifluoroborate salt (eq 2),12
which can undergo Suzuki cross coupling reactions (eq 3).13
In an attempt to optimize the cyclization/boration reaction
further, different lanthanide metallocenes were tested with
1,3-dimethyl-1,3-diaza-2-boracyclopentane and substrate 1
(entry d). The cyclization/boration reaction using the divalent
precatalyst Cp*2Sm‚THF afforded 6 after 18 h, followed by
oxidative workup in 86% yield. Cp*2YMe‚THF did not show
any activity with 1,3-dimethyl-1,3-diaza-2-boracyclopentane.
The precatalysts [CpTMS2LnMe]2 afforded 6 after 18 h at 80
°C in yields ranging from 40% for Ln ) Lu to 74% for Ln
) Sm. The results illustrate that reduced substitution about
the ligand and a larger metal ionic radius contribute to
accelerated cyclization/boration. Considering also the ease
of preparation in comparison to the other lanthanide metal-
locenes,9 we decided to use Cp*2Sm‚THF as the precatalyst
to probe the scope of the cyclization/boration with different
substrates.
The cyclization/boration reaction with 1,3-dimethyl-1,3-
diaza-2-boracyclopentane and substrates 1-4 catalyzed by
Cp*2Sm‚THF afforded, after oxidative workup, the alcohols
6 and 7 containing five-membered rings in yields of 86%
and 64% and the alcohols 7 and 8 containing six-membered
rings in yields of 55% and 52%, respectively (eq 1). The
cyclization/boration reaction is less efficient for the formation
of six-membered rings, as indicated by the decreased yield
of 8 and 9 relative to 6 and 7.
In summary, a cyclization/boration reaction catalyzed by
an organosamarium complex has been developed. This
reaction produced, after oxidative workup, primary alcohols
containing five- and six-membered rings. Although dienes
containing protected alcohol functional groups do not
undergo cyclization/boration utilizing this protocol, further
studies designed to optimize and broaden the scope of this
reaction are under way in our laboratory.
Acknowledgment. We thank Professor Larry G. Sneddon
and Mark J. Pender for many useful suggestions and
discussions and Mr. Jason P. Burke for performing the
reactions in eqs 2 and 3. We also gratefully acknowledge
the National Institutes of Health (GM48580) and Merck &
Co., Inc., for their generous support of this research.
Supporting Information Available: The preparation and
characterization of compounds 1-9 and experimental pro-
cedures. This information is available free of charge via the
Internet at http://pubs.acs.org.
Products 6 and 8 were identified by comparison of the 1H
and 13C NMR spectral data with commercial samples.
Compounds 7 and 9 were isolated as single diastereomers.
The trans stereochemistry was confirmed by comparison of
the spectral data with literature data.10 Unfortunately, we were
unable to perform cyclization/boration on substrates such as
compound 5 containing a protected alcohol utilizing this
OL006841S
(11) (a) Gagne´, M. R.; Nolan, S. P.; Marks, T. J. Organometallics 1990,
9, 1716. (b) Nolan, S. P.; Stern, D.; Marks, T. J. J. Am. Chem. Soc. 1998,
111, 7844.
(12) (a) Burke, J. P. Research in progress. (b) Batey, R. A.; Thadani, A.
N.; Smil, D. V. Org. Lett. 1999, 1, 1683. (c) Batey, R. A.; Thadani, A. N.;
Smil, D. V. Tetrahedron Lett. 1999, 40, 4289. (d) Darses, S.; Michaud, G.;
Geneˆt, J.-P. Eur. J. Org. Chem. 1999, 1875. (e) Vedejs, E.; Fields, S. C.;
Hayashi, R.; Hitchcock, S. R.; Powell, D. R.; Schrimpf, M. R. J. Am. Chem.
Soc. 1999, 121, 2460. (f) Vedejs, E.; Chapman, R. W.; Fields, S. C.; Lin,
S.; Schrimpf, M. R. J. Org. Chem. 1995, 60, 3020. (g) Darses, S.; Michaud,
G.; Geneˆt, J.-P. Tetrahedron Lett. 1998, 39, 5045.
(9) Precatalyst preparation: (a) Evans, W. J.; Grate, J. W.; Choi, H. W.;
Bloom, I.; Hunter, W. E.; Atwood, J. L. J. Am. Chem. Soc. 1985, 107, 941
for Cp*2Sm‚THF. (b) Schumann, H.; Keitsch, M. R.; Demtschuk, J.;
Molander, G. A. J. Organomet. Chem. 1999, 582, 70 for [CpTMS2LnMe]2.
(c) den Haan, K. H.; deBoer, J. L.; Teuben, J. H.; Smeets, W. J. J.; Spek,
A. L. J. Organomet. Chem. 1987, 327, 70 for Cp*2YMe‚THF.
(10) (a) Rieke, R. D.; Xiong, H. J. Org. Chem. 1991, 56, 3109. (b) Fang,
C.; Suemune, H.; Sakai, K. J. Org. Chem. 1992, 57, 4300.
(13) Molander, G. A.; Ito, T. Manuscript submitted.
Org. Lett., Vol. 3, No. 3, 2001
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