reaction conditions, in particular, applicable solvents for ruthe-
nium-catalyzed cyclocarbonylation. We initially examined
solvent effect on ruthenium-catalyzed cyclocarbonylation of
3-cyclohexylhexa-4,5-dien-1-ol 1, which was chosen as a
marginally reactive allenyl alcohol.4c The results are shown in
Table 1. Reaction of 1 with Ru3(CO)12 (3 mol %) in triethy-
lamine under 5 atm of carbon monoxide at 100 °C, the same
condition as those reported,4c afforded an inseparable mixture
of endo-2 and exo-2 (2.1: 1) in 72% (entry 1). Based on the
proposed reaction mechanism,4b triethylamine together with
the Ru catalyst would promote the isomerization of exo- to endo-
isomer. Thus, our efforts were focused on both the improvement
of yield and the effective alkene isomerization. Use of n-butyl
methyl sulfide6 as an additive slightly improved the ratio of
Practical Ruthenium-Catalyzed
Cyclocarbonylation of Allenyl Alcohols in
2,4,6-Collidine Leading to r,ꢀ-Unsaturated
Lactones: Concise Stereoselective Synthesis of
(+)-Isomintlactone
Masayoshi Tsubuki,* Kazunori Takahashi, and
Toshio Honda*
Faculty of Pharmaceutical Sciences, Hoshi UniVersity,
Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan
ReceiVed NoVember 11, 2008
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Huang, H.; Pu, J.-X.; Sun, H.-D. J. Nat. Prod. 2008, 71, 1228–1232. (b)
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Tachibana, M.; Matsui, C.; Takeuchi, Y.; Suzuki, E.; Umezawa, K. Heterocycles
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We have found that ruthenium-catalyzed cyclocarbonylation
of allenyl alcohols in 2,4,6-collidine under atmospheric
pressure of carbon monoxide smoothly proceeds to afford
R,ꢀ-unsaturated five- and six-membered lactones in moderate
to good yields. Furthermore, we have completed a highly
stereoselective synthesis of (+)-isomintlactone by the cy-
clocarbonylation of allenyl alcohol using 2,4,6-collidine.
R,ꢀ-Unsaturated five- to seven-membered lactones not only
constitute a structural feature common to numerous biologically
active natural products,1 but also have been employed as useful
building blocks in organic synthesis.2 There are a large number
of synthetic methods for the R,ꢀ-unsaturated lactones,3 among
which representatives include oxidative syn-elimination of
R-phenylseleno lactones,3a cycloisomerization of γ-keto car-
boxylic acids,3b cyclic carbometalation of alkynes,3c and RCM
reaction of allyl acrylates.3d Recently, Takahashi et al. have
reported an alternative synthetic strategy via ruthenium-catalyzed
cyclocarbonylation of allenyl alcohols,4 in which allenyl alcohols
could react at 100 °C under CO (10 atm) to give R,ꢀ-unsaturated
lactones.
During the course of the synthetic studies toward bipinnatin
J, we studied the conversion of highly functionalized allenyl
alcohol to R,ꢀ-unsaturated five-membered lactone, a γ-buteno-
lide, using ruthenium-catalyzed cyclocarbonylation.5 We suc-
cessfully obtained the γ-butenolide, which constitutes a formal
synthesis of bipinnatin J. Since ruthenium-catalyzed cyclocar-
bonylation is an efficient method for the synthesis of R,ꢀ-
unsaturated lactones, the application of ruthenium-catalyzed
cyclocarbonylation under moderate pressure and short reaction
time would be advantageous for the synthesis of highly densed
natural products. In this regard, we investigated the suitable
1422 J. Org. Chem. 2009, 74, 1422–1425
10.1021/jo8025127 CCC: $40.75 2009 American Chemical Society
Published on Web 12/18/2008