from a variety of aldehydes. However, when these reagents
were applied for the intramolecular HWE reaction, low to
moderate selectivity and/or low yields were generally re-
ported.9,10 For example, Ghosh mainly received the E product
for the synthesis of laulimalide.9a The Z/E ratios were 1:1.7
and 1:2 using our reagent and Still’s reagent, respectively.
After Aristoff’s report,11,12 K2CO3 and 18-crown-6 in toluene
have been used for the Z-selective intramolecular HWE
reaction. In fact, all the intramolecular HWE reactions of
ref 9 used these conditions. Since the reaction conditions
for the Z-selective intramolecular HWE reaction have never
been fully optimized, we decided to define the satisfactory
reaction conditions. Here, we report our results of the
intramolecular HWE reaction containing 12- to 18-membered-
ring lactones.
protected diols 5, followed by deprotection and oxidation
as outlined in Scheme 3. Oxidation of 5 with PCC and the
Scheme 3
Benzyl diphenylphosphonoacetate 2a was prepared by
treatment of diphenyl methylphosphonate with 2 equiv of
LiHMDS in the presence of ClCO2CH2Ph in THF, and the
other phosphonates 2b-d were obtained by heating
(RO)2P(OEt)13 with BrCH2CO2CH2Ph in high yields (Scheme
2). The phosphonoacetic acids 3a-d were prepared by
Scheme 2
following HWE reaction with 4 using LiCl-DBU15,14 gave
E-R,ꢀ-unsaturated esters 12. Reduction of 12 to the alcohols,
esterification with 3, deprotection, and then oxidation gave
the intramolecular HWE subatrates 14 and 15 containing the
E-olefin. Although the yields were not optimized, the
procedure is efficient especially for the diaryl phosphonoac-
etate reagents.
The intramolecular HWE reaction of 9 was summarized
in Table 1.16 The HWE reaction of 9a was performed using
a procedure similar to the intermolecular HWE reaction.8b
That is, 9a was treated with NaH in THF at -60 °C, and
then the mixture was gradually warmed to 0 °C over 1 h.
Only 12% yield of the 15-membered-ring lactone Z-16 was
obtained. The Z/E ratio of all the obtained HWE products is
92:8 (entry 1). The main products were oligomeric (dimeric
and/or trimeric) lactones (58% yield). The formation of
oligomers was suppressed when a THF solution of 9a was
added to a THF solution containing 3 equiv of NaH over
4 h at 0 °C (entry 2). Gladly and somewhat surprisingly, the
Z selectivity did not reduce even at 0 °C, and a 73% yield
of Z-16 was obtained. Z-16 was also efficiently obtained
using NaI-DBU8e as a base in the highest yield (84%) (entry
hydrogenolysis of 2 with Pd/C in 91-99% yields. Diethyl
phosphonoacetic acid 3d was also obtained by hydrolysis
of 4 in 93% yield.
The intramolecular HWE substrates 7-11 were prepared
by esterification of phosphonoacetic acid 3 with mono-THP-
(8) (a) Ando, K. Tetrahedron Lett. 1995, 36, 4105–4108. (b) Ando, K.
J. Org. Chem. 1997, 62, 1934–1939. (c) Ando, K. J. Org. Chem. 1998, 63,
8411–8416. (d) Ando, K. J. Org. Chem. 1999, 64, 8406–8408. (e) Ando,
K.; Oishi, T.; Hirama, M.; Ohno, H.; Ibuka, T. J. Org. Chem. 2000, 65,
4745–4749. (f) Ando, K. J. Synth. Org. Chem., Jpn. 2000, 58, 869–876
.
(9) (a) Ghosh, A. K.; Wang, Y. J. Am. Chem. Soc. 2000, 122, 11027–
11028. (b) Forsyth, C. J.; Ahmed, F.; Cink, R. D.; Lee, C. S. J. Am. Chem.
Soc. 1998, 120, 5597–5598. (c) Gonza´lez, M. A.; Pattenden, G. Angew.
Chem., Int. Ed. 2003, 42, 1255–1258. (d) Williams, D. R.; Kiryanov, A. A.;
Emde, U.; Clark, M. P.; Berliner, M. A.; Reeves, J. T. Angew. Chem., Int.
Ed. 2003, 42, 1255–1258. Williams, D. R.; Clark, M. P. Tetrahedron Lett.
1999, 40, 2291–2294. (e) Ahmed, A.; Hoegenauer, E. K.; Enev, V. S.;
Hanbauer, M.; Kaehlig, H.; Ohler, E.; Mulzer, J. J. Org. Chem. 2003, 68,
3026–3042. (f) Pattenden, G.; Gonzalez, M. A.; Little, P. B.; Millan, D. S.;
Plowright, A. T.; Tornos, J. A.; Ye, T. Org. Biomol. Chem. 2003, 1, 4173–
4208. (g) Smith, A. B., III; Minbiole, K. P.; Verhoest, P. R.; Schelhaas, M.
J. Am. Chem. Soc. 2001, 123, 10942–10953. Smith, A. B., III; Razler, T. M.;
Ciavarri, J. P.; Hirose, T.; Ishikawa, T. Org. Lett. 2005, 7, 4399–4402.
Smith, A. B., III; Razler, T. M.; Meis, R. M.; Pettit, G. R. Org. Lett. 2006,
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(10) Zhang, J.; Xu, X. Tetrahedron Lett. 2000, 41, 941–943.
(11) Aristoff, P. A. J. Org. Chem. 1981, 46, 1954–1957.
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Suh, Y.-G. Tetrahedron Lett. 2006, 47, 6527–6530. (b) Still, W. C.; Gennari,
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(13) Diaryl ethyl phosphites (ArO)2P(OEt) (Ar ) o-MePh, o-t-BuPh)
were prepared using Touchard’s procedure.14
(14) Touchard, F. P.; Capelle, N.; Mercier, M. AdV. Synth. Catal. 2005,
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(15) Blanchette, M. A.; Choy, W.; Davis, J. T.; Essenfeld, A. P.;
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(16) All the HWE products and the reagents described in this paper
were characterized by 400 MHz 1H NMR spectra and mass spectros-
copy. The Z/E ratios were determined by integration of the vinyl proton
signals.
128, 5340–5341
.
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