Titanium(IV) aryloxide catalyzed cyclization reactions of 1,6- and 1,7- dienes [5]

Full text of DOI:10.1021/ja9922680

J. Am. Chem. Soc. 2000, 122, 1223-1224
1223
Table 1. Effect of (RO)4Ti on Catalyzed Cyclisomerization
Reaction of 1,6-Dienes 1a to 2a
Titanium(IV) Aryloxide Catalyzed Cyclization
Reactions of 1,6- and 1,7-Dienes
Sentaro Okamoto1 and Tom Livinghouse*
Department of Chemistry, Montana State UniVersity
entry
(RO)4Ti
yield of 2a (%)a
Bozeman, Montana 59717
1
2
3
4
5
(i-PrO)4Ti
(9)
(38)
(39)
(68)
(14)
(85)b
(85)b
(cyc-HexO)4Ti
(cyc-HexO)4Ti (48 h)
(PhO)4Ti
(2,6-Ph2C6H3O)2TiCl2
(2,6-Me2C6H3O)4Ti
(2,6-Me2C6H3O)4Ti (5 mol %)
ReceiVed July 1, 1999
Transformations of unsaturated compounds mediated by sto-
ichiometric quantities of zirconocene or titanocene complexes
have received widespread acceptance as valuable methods in
organic synthesis, and have been used as key reactions for the
total synthesis of natural products.2 Recently, the generation and
subsequent utilization of low-valent complexes of the type
(RO)2Ti(L)n as alternatives to Cp2M(L)n (M ) Ti, Zr) in many
reactions has been popularized.3,4 With the exception of a few
catalytic reactions,5-7 the vast majority of transformations involv-
6
7c
ing (RO)2Ti(L)n equivalents require stoichiometric amounts of
the reagent.4 Although stoichiometric reactions utilizing inex-
pensive (i-PrO)3TiX reagents often generate intermediates con-
taining nucleophilic Ti-C bonds that can be used for further
manipulations, the discovery of new catalytic processes should
permit the use of specialized RO- ligands for reaction profile
alteration as well as increased efficiency.5e In this context, it is
noteworthy that all of the catalytic transformations involving
(RO)2Ti(L)n complexes recorded to date require the use of at least
stoichiometric amounts of the driving organometallic reagent.5-7
In this communication, we wish to report the (ArO)2Ti-
catalyzed cycloisomerization of 1,6- and 1,7-dienes to methyl-
enecycloalkanes using catalytic amounts of both (ArO)4Ti and a
Grignard reagent.8
In an initial experiment, we found that the reaction of 1,6-
diene 1a with catalytic amounts of Ti(O-i-Pr)4 (10 mol %) and
cyc-C6H11MgCl9 (25 mol %) in THF (0 °C to room temperature,
24 h) afforded methylenecyclopentane 2a (9%), the corresponding
saturated cyclopentane 3a (7%), and recovered 1a (84%) (eq 1
and entry 1 in Table 1). This result suggested that the reaction
could be rendered catalytic since the conversion (combined yield
of 2a and 3a) was greater than the amount of the titanium
complex. Accordingly, we investigated the reaction using several
Ti(OR)4 species to find the appropriate conditions for predominant
production of 2a (entries 1-6, Table 1). It was discovered that
the use of (2,6-Me2C6H3O)4Ti7a as a precatalyst provided 2a in
excellent yield (entry 6) and the amount of this titanium compound
could be reduced (entry 7). As is also revealed from these data,
the nature of the RO group affects the reaction both sterically
and electronically. In addition, the reaction may be subject to
termination by decomposition of active catalyst (entries 2 and
3). Under identical reaction conditions, (2,6-Ph2C6H3O)2TiCl2 did
not provide a good yield of 2a.7 This is presumably due to steric
hindrance of the ArO groups and/or the diminished ability of the
Ti center to form an “ate” complex.
(1) Visiting Research Associate, Montana State University (1998-1999).
(2) (a) Yasuda, H.; Nakamura, A. Angew. Chem., Int. Ed. Engl. 1987, 26,
723. Buchwald, S. L.; Neilsen, R. B. Chem. ReV. 1988, 88, 1047. (b) Negishi,
E. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: Oxford, 1991; Vol. 5, p 1163. (c) Broene, R. D.; Buchwald,
S. L. Science 1993, 261, 1696. Negishi, E.; Takahashi, T. Acc. Chem. Res.
1994, 27, 124. Hanzawa, Y.; Ito, H.; Taguchi, T. Synlett 1995, 299. Ohff, A.;
Pulst, S.; Lefeber, C.; Peulecke, N.; Arndt, P.; Burkalov, V. V.; Rosenthal,
U. Synlett 1996, 111. See also ref 3q. (d) For the stoichiometric use of CpTi-
(CH3)2Cl in synthesis, see: Fairfax, D.; Stein, M.; Livinghouse, T. Organo-
metallics, 1997, 16, 1523. McGrane, P. L.; Livinghouse, T. J. Am. Chem.
Soc. 1993, 115, 11485 and references therein.
(3) For generation and utility of (RO)2Ti(η2-alkene) or (RO)2Ti(η2-alkyne)
derived from Ti(O-i-Pr)4/Grignard reagent and alkene or alkyne, see: (a)
Hamada, T.; Suzuki, D.; Urabe, H.; Sato, F. J. Am. Chem. Soc. 1999, 121,
7342. (b) Takayama, Y.; Okamoto, S.; Sato, F. J. Am. Chem. Soc. 1999, 121,
3559. (c) Urabe, H.; Hamada, T.; Sato, F. J. Am. Chem. Soc. 1999, 121, 2931.
(d) Hareau, G. P.-J.; Koiwa, M.; Hikichi, S.; Sato, F. J. Am. Chem. Soc. 1999,
121, 3640. (e) Urabe, H.; Sato, F. J. Am. Chem. Soc. 1999, 121, 1245 and
references cited therein. Reviews, see: (f) Sato, F.; Urabe, H.; Okamoto, S.
J. Synth. Org. Chem. Jpn. 1998, 56, 424. For generation and utility of (η2-
alkene or -alkyne)Ti(OAr)2: (g) Johnson, E. S.; Balaich, G. J.; Rothwell, I.
P. J. Am. Chem. Soc. 1997, 119, 7685. (h) Johnson, E. S.; Balich, G. J.;
Fanwick, P. E.; Rothwell, I. P. J. Am. Chem. Soc. 1997, 119, 11086 and see
also ref 7.
(4) After the pioneering work by Kulinkovich and co-workers, in which
the alkoxytitanium-alkene complexes were depicted as titanacycloalkene
compounds, (RO)2Ti(IV)[-CH2-CH(R)-] and used as vicinal dianionic species,
it has been discovered that the alkoxytitanium-alkene complexes could be
utilized as a low-valent titanium equivalent via ligand-exchange reactions with
double or triple bond(s) present in the substrates.3,5,6 For exchange reactions
involving double bonds, the intermediate alkoxytitanium-alkene complexes
have been depicted as (RO)2TiII-(η2-alkene).3 Kulinkovich, O. G.; Sviridov,
S. V.; Vasilevskii, D. A.; Pritytskaya, T. S. Zh. Org. Khim. 1989, 25, 2244.
Kulinkovich, O. G.; Sviridov, S. V.; Vasilevskii, D. A.; Savchenko, A. I.;
Prityrskaya, T. S. Zh. Org. Khim. 1991, 27, 294. Lee, J.; Kim, H.; Cha, J. K.
J. Am. Chem. Soc. 1995, 117, 9919. See also: Chaplinski, V.; de Meijere, A.
Angew. Chem., Int. Ed. Engl. 1996, 35, 413 and refs 5a,b,e.
(5) For the use of catalytic amounts of a (RO)2Ti(L)n equivalent in the
synthesis of cyclopropanols, see: (a) Kulinkovich, O. G.; Sviridov, S. V.;
Vasilevskii, D. A. Synthesis 1991, 234. (b) Kulinkovich, O. G.; Vasilevskii,
D. A.; Savchenko, A. I.; Sviridov, S. V. Zh. Org. Khim. 1991, 27, 1428. For
catalytic cyclo-bis-zincation of enynes, see: (c) Montchamp, J.-L.; Negishi,
E. J. Am. Chem. Soc. 1998, 120, 5345. For catalytic carbometalation of dienes,
see: (d) Negishi, E.; Jensen, M. D.; Kondakov, D. Y.; Wang, S. J. Am. Chem.
Soc. 1994, 116, 8404. For ligand modification leading to optically enriched
cyclopropanols, see: (e) Corey, E. J.; Rao, S. A.; Noe, M. C. J. Am. Chem.
Soc. 1994, 116, 9345.
(6) Cha has reported semi-catalytic hydroxycyclopropanation of olefins
using 0.5 equiv of ClTi(O-i-Pr)3 and 5 equiv of Grignard reagents: Lee, J.;
Kang, C. H.; Kim, H.; Cha, J. K. J. Am. Chem. Soc. 1996, 118, 291. Lee, J.;
Kim, H.; Cha, J. K. J. Am. Chem. Soc. 1996, 118, 4198.
Table 2 summarizes representative examples of this reaction
using a variety of diene substrates 1b-i. These results show the
following features of this cyclization: (1) All of the reactions
gave 2-methyl-1-methylenecycloalkanes, i.e., the coupling pro-
(8) Titanocene derivative-catalyzed cyclization of enynes and alkenones
has been reported: Kablaoui, N. M.; Buchwald, S. L. J. Am. Chem. Soc. 1996,
118, 3182. Hicks, F. A.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118, 11688.
Kablaoui, N. M.; Hicks, F. A.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118,
5818; Kablaoui, N. M.; Hicks, F. A.; Buchwald, S. L. J. Am. Chem. Soc.
1997, 119, 4424. Montchamp, J.-L.; Negishi, E. J. Am. Chem. Soc. 1998,
120, 5345. Sturla, S. J.; Kablaoui, N. M.; Buchwald, S. L. J. Am. Chem. Soc.
1999, 121, 1976.
(9) The ratio of Grignard reagent to Ti(OAr)4 is 2:1. The reaction of 1a
with 50 mol % of (2,6-Me2C6H3O)4Ti and 50 mol % of cyc-HexMgCl did
not give cyclized product. In initial investigations, we found that the reaction
could be carried out by using i-PrMgCl, i-BuMgCl, n-BuMgBr, or cyc-
HexMgCl. Among these activators, cyc-HexMgCl gave slightly better yields.
The use of EtMgBr did not provide cyclized product.
(7) (a) (2,6-Me2C6H3O)4Ti was prepared by a modification of the literature
procedure: Durfee, L. D.; Latesky, S. L.; Rothwell, I. P.; Huffman, J. C.;
Folting, K. Inorg. Chem. 1985, 24, 4569. (b) Rothwell has investigated the
cycloisomerization reaction of 1,7-octadiene catalyzed by the bicyclotitana-
cyclopentane compound, derived from (2,6-Ph2C6H3O)TiCl2, 2BuLi, and 1,7-
octadiene, but this titanacycle could not catalyze the cyclization of 1,6-
heptadiene: Waratuke, S. A.; Thorn, M. G.; Hill, J. E.; Waratuke, A. S.;
Johnson, E. S.; Fanwick, P. E.; Rothwell, I. P. J. Am. Chem. Soc. 1997, 119,
8630 and references therein.
10.1021/ja9922680 CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/01/2000

1224 J. Am. Chem. Soc., Vol. 122, No. 6, 2000
Communications to the Editor
Table 2. Cyclisomerization Reaction of 1,6-Dienes Catalyzed by
(2,6-Me2H3O)4Ti and cyc-HexMgCl
Figure 1. Structures 6 and 7.
Scheme 1
reductive elimination of Ti(OR)2 occurs to produce methylenecy-
clopentane 2.12
Sato has reported the quantitative preparation of bicyclotitana-
pentanes (i.e., 6) from 1,6-dienes and a stoichiometric amount of
a Ti(O-i-Pr)4/2 i-PrMgX reagent and these are stable at -50 °C
(Figure 1).3i,j Similarly, Rothwell has reported that the titanium
compound 7 catalyzes the cycloisomerization of 1,7-octadiene
to 2-methyl-1-methylenecyclohexane at high temperature (100
°C), but that the complex is stable enough below room temper-
ature to be isolated.7b Furthermore, the bicyclometallacyclopen-
tanes derived from Cp2TiCl2 or Cp2ZrCl2 and an appropriate
reducing agent are usually stable at up to room temperature for
further manipulations such as CO insertion and electrophilic
functionalization of the Ti-C bond(s) with carbonyl com-
pounds.2,13 In the present transformation, it can be considered that
the nature of the RO group plays an important role. The bulkiness
of the 2,6-Me2C6H3O moiety may decrease the decomposition
rate of the active Ti(II) species, but this ligand is small enough
not to retard â-hydride elimination. In addition, the electron-
deficient character of the phenoxide ligands relative to aliphatic
alkoxy moieties provides an electron-poor Ti center that should
facilitate both â-hydrogen abstraction and alkene coordination.
These stereoelectronic effects enhance the viability of the catalytic
manifold so that efficient cycloisomerization occurs at 0 °C to
ambient temperature.
a Isolated yield. In all entries, a small amount of the saturated
compound 3 (5-10% yield) was produced. b Ratio was determined by
1H NMR and/or GC analysis. c 20 mol % of a Ti compound and 45
mol % of cyc-HexMgCl were used. d The reaction mixture was stirred
for 48 h. 29% of 1f was recovered. e Yield was determined by NMR
analysis of the crude mixture using an internal standard. f For deter-
mination of the stereochemistry, see the Supporting Information.
ceeded in a tail-to-tail fashion; (2) 4-substituted or 4,4-disubsti-
tuted 1,6-dienes are superior substrates for the formation of five-
membered-ring compounds; (3) the reaction can be applied to
the formation of six-membered-ring carbocycles (entry 7); (4)
highly diastereoselective cyclizations can be realized for appropri-
ate substrates (entry 7); (5) heterocycles, such as 2f and 2g, can
be synthesized by this methodology (entries 5 and 6); and (6)
the reaction is not suitable for 1,6-dienes possessing terminal
alkene substitution (entry 8).
It has been widely accepted that alkoxides of the type (RO)4Ti
can be easily reduced by Grignard reagents to provide a (RO)2Ti
equivalent in situ.3-7,10 In addition, Ti(III) hydride complexes are
known to be highly active catalysts for alkene isomerization.11a
In light of these considerations, the active catalyst in the present
reaction is postulated to be a transient complex of the type (2,6-
Me2C6H3O)2Ti(η2-alkene).11b On this basis, a possible catalytic
cycle is illustrated in Scheme 1. Reaction of the (RO)2Ti
equivalent (prepared in situ in the presence of diene) with the
diene substrate should generate a metastable bicyclotitanacyclo-
pentane 4. Complex 4, in turn, undergoes â-hydride elimination
to provide the corresponding Ti-H compound 5, from which
In summary, we have developed a catalyst system derived from
(2,6-Me2C6H3O)4Ti and RMgX and shown this to be effective
for cycloisomerization reactions of 1,6- and 1,7-dienes. The
present transformation provides a highly efficient means to
synthesize methylenecycloalkanes, including heterocyclic com-
pounds.14
Supporting Information Available: Preparation details and experi-
mental results (PDF). This material is available free of charge via the
Internet at http://pubs.acs.org.
JA9922680
(10) (RO)2Ti equivalents are believed to be stabilized as alkene or alkyne
complexes such as (η2-alkene)Ti(OR)2, see refs 3-7.
(12) A similar mechanism to explain the formation of 2-methyl-1-
methylenecycloalkanes from bicyclometallacyclopentenes has been dis-
cussed: (a) Smith, G.; McLain, S. J.; Schrock, R. R. J. Organomet. Chem.
1980, 202, 269. (b) Yamamoto, Y.; Ohkoshi, N.; Kameda, M.; Itoh, K. J.
Org. Chem. 1999, 64, 2178, and refs 7 and 13.
(13) Thermal decomposition of bicyclic titana- and zirconacyclopentanes
to provide 2-methyl-1-methylenecycloalkanes has been reported: McDermott,
J. X.; Wilson, M. E.; Whitesides, G. M. J. Am. Chem. Soc. 1976, 98, 6529.
Takahashi, T.; Kotora, M.; Kasai, K. J. Chem. Soc., Chem. Commun. 1994, 2693.
(14) For additional examples of transition metal-catalyzed cycloisomer-
ization of 1,6-dienes, see: Radetich, B.; RajanBabu, T. V. J. Am. Chem. Soc.
1998, 120, 8007. Heumann, A.; Moukhliss, M. Synlett 1998, 1211. Christoffers,
J.; Bergman, R. G. J. Am. Chem. Soc. 1996, 118, 4715. Piers, W. E.; Shapiro,
P. J.; Bunel, E. E.; Bewcaw, J. E. Synlett 1990, 74.
(11) (a) Akita, M.; Yasuda, H.; Nagasuna, K.; Nakamura, A. Bull. Chem.
Soc. Jpn. 1983, 56, 554 and references therein. (b) In control experiments,
dienes 1d and 1g were subjected to cyclization in the presence of a Cp2Ti-H
source derived from Cp2TiCl2 (5 mol %) and n-BuMgBr (15 mol %). In the
case of 1d, 2d was obtained admixed with the isomerized product 8 (2d:8 )
49:21) whereas for 1g, the E,E-diene 9 was obtained in 95% isolated yield.
The absence of similar alkene isomerization products in the present (ArO)4Ti/
RMgCl-catalyzed diene cyclizations is therefore inconsistent with the par-
ticipation of a Ti(III) intermediate in the catalyic cycle.