LETTER
1,3-Disubstituted Allenes
907
Nishida, M.; Kutsuwa, K.; Murahashi, S.; Naota, T. Org.
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achieved by treatment of 10 with n-BuLi followed by
ClCO2Et. Conversion of alkyne to iodoalkene was first at-
tempted under the conditions of Ma and Lu13 as in the syn-
thesis of 6. However, in this case we found that it was
difficult to separate the desired product from other unde-
sirable side products. To circumvent this problem, an al-
ternative approach was adopted. The ester group was first
reduced with DIBAL-H to the corresponding alcohol. The
intermediate propargyl alcohol was then treated14 with
Red-Al followed by I2 to give 12 without complications.
Oxidation with Dess–Martin periodinane and Wittig reac-
tion with Ph3P=CHCO2Me afforded diene 13. The TBS
protecting group was replaced with an acetyl group, pro-
viding the desired precursor 14.15 The key elimination
was then performed under the optimal conditions estab-
lished in the conversion of 6a to 7. With an additional C–
C double bond and an ester functionality in conjugation
with the iodoalkene functionality, the 1,2-elimination oc-
curred at a much faster rate, affording the desired product
ent-2 in 91% yield.
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In brief, a new elimination approach to the enantioselec-
tive synthesis of 1,3-disubtituted allenes from 3-acetoxy-
2-iodo-prop-1-ene derviatives has been developed. The
results show experimentally for the first time that the
elimination of the alkenyl iodides may proceed with a
high level of stereoselectivity and in good product yield in
the presence of i-PrMgBr as the reagent. The iodoalkenyl
functionality in the substrates can be either isolated or in
conjugation with another C–C double bond. Compared
with the alkenyl sulfoxides,4b silanes,3j and stannanes3k,4a
used in the previous elimination protocols, the iodo sub-
strates are synthetically more readily accessible, less toxic
and of better atom/chirality16 economy. All these make
the present protocol a good complement to the existing
methods for the enantioselective construction of 1,3-di-
substituted allenes.17
(4) For elimination of a-acetoxyl alkenyl tributyltin, see:
(a) Konoik, T.; Araki, Y. Tetrahedron Lett. 1988, 29, 1355;
cf. also ref. 3k . For elimination of a-acetoxyl alkenyl
sulfoxides, see: (b) Satoh, T.; Itoh, N.; Watanabe, S.; Koike,
H.; Matsuno, H.; Matsuda, K.; Yamakawa, K. Tetrahedron
1995, 51, 9327. (c) Satoh, T.; Kuramochi, Y.; Inoue, Y.
Tetrahedron Lett. 1999, 40, 8815. (d) Satoh, T.; Hanaki, N.;
Kuramochi, Y.; Inoue, Y.; Hosoya, K.; Sakai, K.
Tetrahedron 2002, 58, 2533.
(5) For clarity, synthesis of 6a–c is given in the Supporting
Information.
(6) Zhu, L.; Wehmeyer, R. M.; Rieke, R. D. J. Org. Chem. 1991,
56, 1445.
(7) (a) Rieke, R. D. Science 1989, 246, 1260. (b) Rieke, R. D.;
Hanson, M. V. Tetrahedron 1997, 53, 1925. (c) Lee, J.;
Velarde-Ortiz, R.; Guijarro, A. R.; Wurst, J.; Rieke, R. D.
J. Org. Chem. 2000, 65, 5428.
Supporting Information for this article is available online at
(8) Hässig, R.; Seebach, D.; Siegel, H. Chem. Ber. 1984, 117,
1877.
(9) Although i-PrMgBr-mediated elimination of sulfoxides are
known (cf. ref. 4b,c), it has never been utilized (to our
knowledge) for elimination of a-acetoxyalkenyl halides.
(10) (a) Krasovskiy, A.; Knochel, P. Angew. Chem. Int. Ed. 2004,
43, 3333. (b) Krasovskiy, A.; Straub, B.; Knochel, P.
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(11) Lower level of functional-group tolerance is also a major
concern here, although the simultaneous cleavage of the
terminal Ac protecting group is beneficial in this synthesis.
(12) (a) Babudri, F.; Fiandanese, V.; Hassan, O.; Punzi, A.; Naso,
F. Tetrahedron 1998, 54, 4327. (b) The substrate utilized in
this work was conveniently derived by a Novezyme 435
Acknowledgment
Financial support from the National Basic Research Program of
China (973 Program) (2010CB833200), National Natural Science
Foundation of China (20672129, 20621062, 20772143), and the
Chinese Academy of Sciences (‘Knowledge Innovation’,
KJCX2.YW.H08) is gratefully acknowledged.
References and Notes
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Synlett 2010, No. 6, 905–908 © Thieme Stuttgart · New York