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S. Matsumoto et al.
LETTER
103, 2861. (d) Davies, H. W. L.; Manning, J. R. Nature
the methyl ester to a primary alcohol proceeded in the
same reaction vessel.
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In summary, we have accomplished an efficient asymmet-
ric total synthesis of (–)-dehydrodiconiferyl alcohol (1) in
13 steps starting from commercially available guaiacol.
The key reaction was a rhodium-catalyzed diastereoselec-
tive C–H insertion reaction, developed by us, which gave
ready access to the optically active trans-disubstituted di-
hydrobenzofuran ring. Subsequent incorporation of a C3
unit by Heck reaction, followed by reductive manipula-
tion completed the short-step synthesis. This route should
be easily adaptable to the synthesis of other related neolig-
nans. The availability of such compounds in ample
amounts would facilitate detailed investigation of the bio-
logical activities of 1 and its congeners.
(13) Davies, H. M. L.; Hansen, T. J. Am. Chem. Soc. 1997, 119,
9075.
(14) García-Muñoz, S.; Álvarez-Corral, M.; Jiménez-González,
L.; López-Sánchez, C.; Rosales, A.; Muñoz-Dorado, M.;
Rodríguez-García, I. Tetrahedron 2006, 62, 12182.
(15) (a) Saito, H.; Oishi, H.; Kitagawa, S.; Nakamura, S.; Anada,
M.; Hashimoto, S. Org. Lett. 2002, 4, 3887. (b) Natori, Y.;
Tsutsui, H.; Sato, N.; Nakamura, S.; Nambu, H.; Shiro, M.;
Hashimoto, S. J. Org. Chem. 2009, 74, 4418.
Supporting Information for this article is available online at
Acknowledgment
(16) Davies, H. M. L.; Grazini, M. V. A.; Aouad, E. Org. Lett.
2001, 3, 1475.
(17) Baum, J. S.; Shook, D. A.; Davies, H. M. L.; David, H. D.
This work was financially supported by a Grant-in-Aid for Scienti-
fic Research on Priority Areas 12045232 from the Ministry of Edu-
cation, Culture, Sports, Science and Technology (MEXT) of Japan.
Synth. Commun. 1987, 17, 1709.
(18) This reaction was found to be sensitive to the reaction
temperature: when the reaction was carried out at 0 °C, the
chemical yield was decreased significantly due to the
formation of an a-hydroxylated byproduct. Interestingly,
reverse diastereoselectivity was observed at –20 °C, giving
the product in 57% yield with a cis-substituted isomer being
major (2.4:1 dr). Although the reason is unclear, these results
suggest that careful control of the reaction temperature is
necessary to ensure that the desired reaction pathway
operates.
(19) As for the detailed discussion on the determination of the
stereochemistry, see the Supporting Information.
(20) Hirai, N.; Okamoto, M.; Udagawa, H.; Yamamuro, M.;
Kato, M.; Koshimizu, K. Biosci. Biotechnol. Biochem. 1994,
58, 1679.
(21) It seems likely that the observed absolute stereochemistry is
mainly governed by the chiral auxiliary, and not by the chiral
Rh catalyst, in accord with our previous results.12
(22) Heck, R. F. Org. React. 1982, 27, 345.
(23) Ganem, B.; Small, V. R. Jr. J. Org. Chem. 1974, 39, 3728.
(24) Spectral Data for 1
References and Notes
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IR (neat): 818, 856, 966, 1034, 1146, 1215, 1275, 1331,
1464, 1496, 1518, 1603, 1703, 2361, 2926, 3414 cm–1.
1H NMR (500 MHz, acetone-d6): d = 2.82 (s, 2 H), 3.52 (q,
J = 6.3 Hz, 1 H), 3.81 (s, 3 H), 3.83–3.90 {m, 5 H [a methoxy
group (3 H) was included at d = 3.85 ppm as a singlet peak]},
4.20 (dt, J = 1.2, 5.2 Hz, 2 H), 5.55 (d, J = 6.3 Hz, 1 H), 6.23
(td, J = 5.2, 16.0 Hz, 1 H), 6.51 (d, J = 16.0 Hz, 1 H), 6.80
(d, J = 8.0 Hz, 1 H), 6.87 (dd, J = 1.7, 8.0 Hz, 1 H), 6.94 (d,
J = 1.2 Hz, 1 H), 6.97 (s, 1 H), 7.03 (d, J = 1.7 Hz, 1 H), 7.59
(s, 1 H). 13C NMR (125 MHz, acetone-d6): d = 54.0, 55.4,
55.5, 62.6, 63.8, 87.7, 109.6, 110.8, 114.8, 115.2, 118.8,
127.6, 129.6, 129.7, 131.1, 133.6, 144.4, 146.5, 147.5,
148.1. MS–FAB: m/z = 358 [M]+. HRMS: m/z calcd for
(10) For reviews of C–H insertion reactions, see: (a) Doyle, M.
P.; Mckervey, M. A.; Ye, T. Modern Catalytic Methods for
Organic Synthesis with Diazo Compounds: From
23
C20H22NaO6 [M + Na]+: 381.1314; found: 381.1309. [a]D
–45.9 (c 2.67, acetone).
Cyclopropanes to Ylides; Willey: New York, 1998.
(b) Taber, D. F.; Stiriba, S.-E. Chem. Eur. J. 1998, 4, 990.
(c) Davies, H. M. L.; Beckwith, R. E. J. Chem. Rev. 2003,
Synlett 2012, 23, 1082–1084
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