Allenation of Carbonyl Compounds with Alkenyltitanocene Derivatives

Full text of DOI:10.1021/jo9620876

7
82
J . Org. Chem. 1997, 62, 782-783
Ta ble 1. Allen a tion of Ca r bon yl Com p ou n d s w ith
Allen a tion of Ca r bon yl Com p ou n d s w ith
Alk en yltita n ocen e Der iva tives
Alk en yltita n ocen es 14-16
titanocene
R1
ketone
Nicos A. Petasis* and Yong-Han Hu
entry
R2
R3
R4
allene
yield (%)
Department of Chemistry and Loker Hydrocarbon Research
Institute, University of Southern California,
Los Angeles, California 90089-1661
1
2
14a
14b
14c
15a
15a
15b
15b
15c
16a
16a
H
H
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Me
Ph
Me
Ph
Ph
6a
6b
6c
6a
6d
6b
6e
6f
89
83
79
89
86
88
80
85
84
89
H
Me
Me
H
3
Me
H
4
Received November 7, 1996
5
H
H
6
H
Me
Me
Me
H
The conversion of carbonyl compounds 1 to olefins 3
via titanocene alkylidene intermediates 2 is an important
process with numerous applications in organic synthesis.1
In recent years, we have been involved with the develop-
ment of new and practical methods for carrying out this
type of titanium-mediated transformation, which is suit-
able not only for the olefination of aldehydes and ketones
7
H
8
Me
H
9
Me
Ph
6a
6d
10
H
H
in a similar manner. These compounds, however, pre-
pared from titanocene dichloride (7) with 2 equiv of an
alkenylmagnesium bromide 10, could be reacted in situ
at 0 °C with carbonyl compounds 4 to give the corre-
sponding allenes (6). Similarly, the alkylalkenyl ti-
tanocenes 15 and 16, prepared from the monochloro
titanocenes 11-13, were also quite unstable for normal
isolation.5 These mixed derivatives, which could be
beneficial in cases involving more valuable alkenyl
groups, can be prepared by adding 1 equiv of 10 to
preformed 116 or 127 or by the one-pot consecutive
addition of 1 equiv of 10 to form 13, followed by the
addition of 1 equiv of the second organomagnesium
bromide. Despite the facile decomposition of 14-16, a
useful allenation process can still be accomplished if these
alkenyl titanocenes are prepared at low temperature and
used directly without isolation.8
2
but also for heteroatom-substituted carbonyls. Herein
we report the analogous conversion of aldehydes and
ketones 4 to allenes 6 via a titanocene alkenylidene
intermediate 5.
The bis(pentamethylcyclopentadienyl)titanium vi-
nylidene analog of 5 was studied extensively by Beck-
haus.3 Although this species reacted with alkynes to
give the corresponding titanacyclobutenes, when it was
reacted with carbonyl compounds it generated a ti-
tanocene enolate species instead of allenes.3d A similar
carbonyl enolization was previously observed with the
bis(pentamethylcyclopentadienyl) analog of 2.4 In con-
trast, as described below, carbonyl allenations proceed
quite efficiently with the less hindered titanocene alk-
enylidene intermediate 5, formed in situ from several
alkenyltitanocene precursors.
3g
Although some of the hydrocarbyltitanocenes that we
used as precursors of 2 (e.g., 8,2 9 ) are quite stable at
room temperature and can even tolerate air and water,
the analogous precursors of 5, namely the dialkenyl
titanocenes 14, are too unstable and could not be isolated
a
2d
(
1) (a) Pine, S. H. Org. React. 1993, 43, 1. (b) Stille, J . R. In
Comprehensive Organometallic Chemistry II; Abel, E. W., Stone, F.
G. A., Wilkinson, G., Eds.; Pergamon: Oxford, 1995; Vol. 12, p 577.
Tables 1 and 2 show several examples of this chemis-
try, which gives good yields of allenes from a variety of
(2) (a) Petasis, N. A.; Bzowej, E. I. J . Am. Chem. Soc. 1990, 112,
6
392. (b) Petasis, N. A.; Bzowej, E. I. U.S. Patent 5087790 A, 1992. (c)
Petasis, N. A.; Bzowej, E. I. J . Org. Chem. 1992, 57, 1327. (d) Petasis,
N. A.; Akritopoulou, I. Synlett 1992, 665. (e) Petasis, N. A.; Bzowej, E.
I. Tetrahedron Lett. 1993, 34, 943. (f) Petasis, N. A.; Lu, S. P.
Tetrahedron Lett. 1995, 36, 2393. (g) Petasis, N. A.; Staszewski, J . P.;
Fu, D.-K. Tetrahedron Lett. 1995, 36, 3619. Petasis, N. A.; Lu, S.-P.;
Bzowej, E. I.; Fu, D.-K.; Staszewski, J . P.; Akritopoulou-Zanze, I.;
Patane, M. A.; Hu, Y.-H. Pure Appl. Chem. 1996, 67, 667.
(5) Even the corresponding bis(pentamethylcyclopentadienyl)vinyl
titanocenes decompose readily at or below room temperature: Luinstra,
G. A.; Teuben, J . H. Organometallics 1992,11, 1793.
(6) Rausch, M. D.; Gordon, H. B. J . Organomet. Chem. 1974, 74,
85.
(7) Petasis, N. A.; Fu, D.-K. J . Am. Chem. Soc. 1993, 115, 7208.
(8) Typical procedure (Table 1, entry 2): To a solution of titanocene
dichloride (500 mg, 2.0 mmol) in THF (20 mL) stirred at -40 °C under
nitrogen was added dropwise 1-propenylmagnesium bromide (8.03 mL,
0.5 M solution in THF, 4.0 mmol). After the mixture was warmed to 0
°C over 1.5 h, acetophenone (0.117 mL, 1.0 mmol) was added, and
stirring was continued at rt monitored by TLC. Concentration of the
solution (to 1 mL), dilution with hexane (30 mL), removal of the
titanocene byproduct by filtration, solvent evaporation, and flash
column chromatography (silica, hexane) gave the allene product (120
mg, 83%).
(
3) (a) Beckhaus, R.; Thiele, K. H.; Stroehl, D. J . Organomet. Chem.
1
989, 369, 43. (b) Beckhaus, R.; Flatau, S.; Trojanov, S.; Hofmann, P.
Chem. Ber. 1992, 125, 291. (c) Beckhaus, R.; Oster, J .; Wagner, T.
Chem. Ber. 1992, 127, 1003. (d) Beckhaus, R.; Strauss, I.; Wagner, T.
J . Organomet. Chem. 1994, 464, 155. (e) Beckhaus, R.; Sang, J .; Oster,
J .; Wagner, T. J . Organomet. Chem. 1994, 484, 179. (f) Beckhaus, R.;
Oster, J .; Loo, R. J . Organomet. Chem. 1995, 501, 321. (g) Beckhaus,
R.; Sang, J .; Wagner, T.; Ganter, B. Organometallics 1996, 15, 1176.
(
4) Bertz, S. H.; Dabbagh, G.; Gibson, C. P. Organometallics 1988,
7
, 563.
S0022-3263(96)02087-7 CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 4, 1997 783
Ta ble 2. Allen a tion of ca r bon yl com p ou n d s w ith
a lk en yl tita n ocen es 15a a n d 16a
process is more difficult on these carbonyls, due to facile
product decomposition.
The intermediacy of a titanocene vinylidene complex
5
was confirmed by reacting 15a with bis(trimethylsilyl)-
acetylene to form the corresponding titanacyclobutene
adduct 17. Similar to tris(trimethylsilyl)titanacyclo-
butene,2g reaction of 17 with acetophenone gave allene
6
a in good yield.
Overall, this titanium-mediated carbonyl allenation
process is a convenient and efficient way to prepare a
variety of allenes and may also be suitable for the
synthesis of more functionalized derivatives. Unlike
other methods for the synthesis of allenes,10 which often
involve multiple steps or form mixtures with alkynes,
1
1
dienes, or other byproducts, the allenation of carbonyls
offers a direct and versatile approach to this increasing
1
1a
useful functionality. While earlier work by Negishi
and Grubbs1 has shown the viability of titanium-
mediated carbonyl allenations, the method described
herein offers a simple and experimentally more conve-
nient approach to this process.
1b
Ack n ow led gm en t. Support of this work by the
National Institutes of Health (RO1-GM 45970) is grate-
fully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Additional experi-
mental procedures and spectroscopic data of selected com-
pounds (4 pages).
carbonyl compounds.9 The reaction is quite clean and
works well with several types of ketones, including aryl,
diaryl, and nitroaryl, as well as R,â-unsaturated carbonyl
derivatives and readily enolizable ketones. Moreover,
this process selectively allenates ketonic carbonyls in the
presence of ester carbonyls (Table 2, entry 5). With 1,2-
diketones (Table 2, entry 6), both carbonyls can be
allenated to form the corresponding diallene product.
J O9620876
(10) (a) Landor, S. R. The Chemistry of the Allenes; Landor, S. R.,
Ed.; Academic Press: New York, 1982; Vols. 1-3. (b) Schuster, H. F.;
Coppola, G. M. Allenes in Organic Synthesis; J ohn Wiley & Sons: New
York, 1984. (c) Patai, S., Ed. The Chemistry of Ketenes, Allenes and
Related Compounds; J ohn Wiley & Sons: New York, 1988; Vols. 1-2.
(11) (a) Yoshida, T.; Negishi, E. J . Am. Chem. Soc. 1981, 103, 1276.
(b) Buchwald, S. L.; Grubbs, R. H. J . Am. Chem. Soc. 1983, 105, 5490.
Although titanium-mediated olefinations generally work
well with esters and lactones,1,2 the present allenation
(c) Reynolds, K. A.; Dopico, P. G.; Sundermann, M. J .; Hughes, K. A.;
Finn, M. G. J . Org. Chem. 1993, 58, 1298. (d) Tucker, C. E.; Greve, B.;
Klein, W.; Knochel, P. Organometallics 1994, 13, 94.
(9) All products gave satisfactory spectroscopic and analytical data.