Preparation of titanated alkoxyallenes from 3-alkoxy-2-propyn-1-yl carbonates and (η2-propene)Ti(O-i-Pr)2 as an efficient ester homoaldol equivalent

Article abstract of DOI:10.1021/ol006142f

(equation presented) 3-Alkoxy-2-propyn-1-yl carbonates (2) react with a divalent titanium reagent (η²-propene)Ti(O-i-Pr)₂ to afford titanated alkoxyallenes 1 which, in turn, react with aldehydes regiospecifically to provide the corresponding γ-addition products in good to excellent yields, thus affording a convenient method for synthesizing γ-hydroxy esters 3 and/or γ-butyrolactones 4.

Full text of DOI:10.1021/ol006142f

ORGANIC
LETTERS
2000
Vol. 2, No. 15
2369-2371
Preparation of Titanated Alkoxyallenes
from 3-Alkoxy-2-propyn-1-yl Carbonates
and (η2-Propene)Ti(O-i-Pr)2 as an
Efficient Ester Homoaldol Equivalent
Takeshi Hanazawa, Sentaro Okamoto, and Fumie Sato*
Department of Biomolecular Engineering, Tokyo Institute of Technology,
4259 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa 226-850, Japan
fsato@bio.titech.ac.jp
Received June 1, 2000
ABSTRACT
3-Alkoxy-2-propyn-1-yl carbonates (2) react with a divalent titanium reagent (η2-propene)Ti(O-i-Pr)2 to afford titanated alkoxyallenes 1 which,
in turn, react with aldehydes regiospecifically to provide the corresponding γ-addition products in good to excellent yields, thus affording a
convenient method for synthesizing γ-hydroxy esters 3 and/or γ-butyrolactones 4.
In 1993, titanated methoxyallene was introduced as a novel
ester homoenolate equivalent. Thus, Dorsch and co-workers
Scheme 1
reported that successive treatment of methoxyallene with
n-butyllithium and ClTi(O-i-Pr)3 furnishes titanated meth-
oxyallene and that this reacts with some aldehydes with
excellent regioselectivity to afford, after acidic hydration of
the addition product, the corresponding γ-lactone as shown
in Scheme 1.1-3 However, this method suffers from two
drawbacks. First, to achieve a satisfactory yield and high
γ-selectivity, the transmetalation reaction step from the
lithium to the titanium needs to be carried out for as long as
14 hours at very low temperatures of -100 to -78 °C.
Second, the regioselectivity is highly dependent on alde-
hydes; while the reaction with R-amino aldehydes afforded
γ-addition products highly predominantly, the reaction with
(1) Hormuth, S.; Reissig, H.-U.; Dorsch, D. Angew. Chem., Int. Ed. Engl.
1993, 32, 1449.
(2) Titanium ester homoenolates: Nakamura, E.; Oshino, H.; Kuwajima,
I. J. Am. Chem. Soc. 1986, 108, 3745. Nakamura, E.; Kuwajima, I. J. Am.
Chem. Soc. 1983, 105, 651. Goswami, R. J. Org. Chem. 1985, 50, 5907.
(3) Reviews for homoenolates and their equivalents, see: Kuwajima, I.;
Nakamura, E. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming,
benzaldehyde provided almost equal amounts of the R- and
I., Eds.; Pergamon: Oxford, 1991; Vol. 2, p 441. Kuwajima, I.; Nakamura,
γ-addition products (see Scheme 1).
Recently, we developed an efficient and practical method
for preparing allenyltitanium complexes by the reaction of
E. Top. Curr. Chem. 1990, 155, 1. Ryu, I.; Sonoda, N. Synth. Org. Chem.,
Jpn. 1985, 43, 112. Werstiuk, N. H. Tetrahedron 1983, 39, 205. Katritzky,
A. R.; Piffl, M.; Lang, H.; Anders, E. Chem. ReV. 1999, 99, 665. See also:
Hoppe, D. Angew. Chem., Int. Ed. Engl. 1984, 23, 932.
10.1021/ol006142f CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/28/2000

propargyl alcohol derivatives such as acetates or carbonates
with the divalent titanium reagent (η2-propene)Ti(O-i-Pr)2,
generated in situ from Ti(O-i-Pr)4 and 2 equiv of i-PrMgX,
which proceeds via an oxidative addition pathway.4,5 We
anticipated that titanated alkoxyallenes 1 with a different kind
of alkoxy group might be prepared from (η2-propene)Ti(O-
i-Pr)2 and readily available 3-alkoxy-2-propyn-1-yl carbon-
ates (2) (Scheme 2) and that among the obtained titanated
Scheme 4
Scheme 2
the corresponding γ-hydroxy ester 3 and/or γ-lactone 4 by
treatment with aqueous 1 N HCl as shown in Scheme 4.
These results strongly indicated that titanated alkoxyallenes
1 with primary and secondary alkoxy groups can be readily
prepared from the corresponding 2 and that they serve as an
efficient ester homoenolate equivalent. Compound 2a seemed
to be somewhat unstable for column chromatography on
silica gel, and thus, the isolated yield of 2a was lower than
that of 2b as shown in Scheme 3. We, therefore, used
titanium reagent 1b derived from 2b for further reaction with
other aldehydes. The results are summarized in Table 1.
alkoxyallenes we could find one having the proper OR
moiety which would react with aldehydes with excellent
γ-selectivity, irrespective of the aldehyde.
The compounds 2a, 2b, and 2c where RO is n-BuO,
c-C6H11O, and t-BuO, respectively, were synthesized starting
from 1,1,2-trichloroethylene, paraformaldehyde, and the
corresponding alcohol according to the reported two-step
reaction sequence shown in Scheme 3.6 The successive
Table 1. Reaction of Alkoxyallenyltitanium 1b with Carbonyl
Compounds
Scheme 3
treatment of 2a or 2b with (η2-propene)Ti(O-i-Pr)2 and
benzaldehyde provided the corresponding γ-addition product
exclusively in excellent yield as shown in Scheme 4 (R-
addition product was not observed); however, the anticipated
titanated alkoxyallene was scarcely generated from 2c under
the same reaction conditions presumably due to the larger
steric requirement of the tertiary alkoxy group. The γ-ad-
dition products obtained here could be easily converted to
(4) Nakagawa, T.; Kasatkin, A.; Sato, F. Tetrahedron Lett. 1995, 36,
3207. Yoshida, Y.; Nakagawa, T.; Sato, F. Synlett 1996, 437. Kasatkin,
A.; Sato, F. Angew. Chem., Int. Ed. Engl. 1996, 35, 2848. An, D. K.;
Okamoto, S.; Sato, F. Tetrahedron Lett. 1998, 39, 4861. An, D. K.;
Hirakawa, K.; Okamoto, S.; Sato, F. Tetrahedron Lett. 1999, 40, 3737.
Okamoto, S.; An, D. K.; Sato, F. Tetrahedron Lett. 1998, 39, 4551. An, D.
K.; Okamoto, S.; Sato, F. Tetrahedron Lett. 1998, 39, 4555.
a Workup conditions: A, 1 N HCl (aq), THF, room temperature, 1 h; B,
1 N HCl (aq), THF, room temperature then, after extractive workup, the
crude product was treated with NaH, THF, 0 °C to room temperature. b The
aldehyde was added to the reaction mixture as a THF solution. c Both 3
and 4 thus obtained consist of two diastereomers in a ratio of 60:40. d Similar
diastereoselectivity was reported in the reaction shown in Scheme 1.
(5) For reviews for synthetic reactions mediated by (η2-propene)Ti(O-
i-Pr)2, see: Sato, F.; Urabe, H.; Okamoto, S. Pure Appl. Chem. 1999, 71,
1511. Sato, F.; Urabe, H.; Okamoto, S. Synlett 2000, 753. Sato, F.; Urabe,
H.; Okamoto, S. J. Synth. Org. Chem. Jpn. 1998, 56, 424.
(6) Porter, N. A.; Dussault, P.; Breyer, R. A.; Kaplan, J.; Morelli, J.
Chem. Res. Toxicol. 1990, 3, 236. Moyano, A.; Charbonnier, F.; Greene,
A. E. J. Org. Chem. 1987, 52, 2919.
It can be seen from Table 1 that 1b reacts with a variety
of aldehydes at the γ-position exclusively, thus affording 3
2370
Org. Lett., Vol. 2, No. 15, 2000

and/or 4 in excellent yield. However, ketones did not react
even though the reaction temperature was warmed to room
temperature, presumably owing to their steric hindrance
(entry 6). The results shown in Table 1 indicate the following
other characteristic features of the reaction: 1b works as
highly chemoselective ester homoenolate equivalent; thus,
functional groups present in aldehydes such as a cyano or
an ester group were tolerated (entries 7 and 8). For the
diasteroselectivity of the reaction with R-substituted alde-
hydes, the reaction with R-amino aldehydes proceeded with
high diastereoselectivity to afford an anti-addition product
highly predominantly (entry 10), as is the case shown in
Scheme 1,1 while R-silyloxy aldehydes gave a rather low
selectivity (entry 9).
mixture of the corresponding addition products in a ratio of
2.5:1 (Scheme 6).7-9 Although the diastereoselectivity was
Scheme 6
The reaction can be extended to the preparation of a
â-substituted ester homoenolate equivalent. Thus, as shown
in Scheme 5, reaction of the carbonates with a substituent
moderate, it may be improved by selecting a proper chiral
alkoxy group, and further investigation to this end is
underway in our laboratory.
In summary, a convenient ester homoenolate equivalent,
titanated alkoxyallenes, can be readily prepared from 3-alkoxy-
2-propyn-1-yl carbonates and (η2-propene)Ti(O-i-Pr)2.
Scheme 5
Supporting Information Available: Experimental pro-
1
cedures and H NMR and 13C NMR data for compounds
2b, 3 (R′ ) Ph), and 4 (R′ ) Ph). This material is available
free of charge via the Internet at http://pubs.acs.org.
OL006142F
at the propargyl position with (η2-propene)Ti(O-i-Pr)2 and
the following treatment with aldehydes afforded â,γ-disub-
stituted γ-lactones.7
Similarly, successive treatment of propargyl carbonate 2d
derived from trans-2-phenylcyclohexanol with (η2-propene)-
Ti(O-i-Pr)2 and benzaldehyde afforded a diastereomeric
(7) The starting carbonate for the reaction of Scheme 5 and Scheme 6
could readily be prepared from the corresponding alcohol and aldehyde
according to a similar procedure shown in Scheme 3 in 70% and 72% overall
yield, respectively.
(8) The ratio was determined by 1H and 13C NMR analyses. The
stereochemistries of the products were not determined.
(9) For a review of chiral homoenolate equivalents, see: Ahlbrecht, H.;
Beyer, U. Synthesis 1999, 365.
Org. Lett., Vol. 2, No. 15, 2000
2371