Chemistry Letters 2000
1181
References and Notes
1
Representative examples of biologically active tertiary alcohol
derivatives: Cinatrin C, Integerrimine, Harringtonine, K-252a,
Forstriecin, Viridiofungin, Erythromicin, and Zaragozic acid:
References cited in the literature, D. A. Evans, C. S. Burgey, M. C.
Kozlowski, and S. W. Tregay, J. Am. Chem. Soc., 121, 686 (1999).
Biological methods: K. E. Henegar, S. W. Ashford, T. A. Baughan,
J. C. Sih, and R. -L. Gu, J. Org. Chem., 62, 6588 (1997);O. Jimenez,
M. P. Bosch, and A. Guerrero, J. Org. Chem., 62, 3496 (1997).
Biological methods: M. Takagi, N. Uemura, and K. Furuhashi, Ann.
N. Y. Acad. Sci., 613, 697 (1990); V. J. Subramanian, Ind.
Microbiol., 1, 119 (1986); W. Reineke, W. Otting, and H.-J.
Knackmuss, Tetrahedron, 34, 1707 (1978); J. T. Rossiter, S. R.
Williams, A. E. G. Cass, and D. W. Ribbons, Tetrahedron Lett., 28,
2
3
5
173 (1987).
Chemical methods: B. D. Brandes and E. N. Jacobsen, J. Org.
Chem., 59, 4378 (1994); T. Fukuda, R. Irie, and T. Katsuki, Synlett,
1
995, 197; D. Yang, M.-K. Wong, Y.-C. Yip, X.-C. Wang, M.-W.
Tang, J.-H. Zheng, and K.-K. Cheung, J. Am. Chem. Soc., 120, 5943
1998); Y. Gao, R.M. Hanson, J. M. Klunder, S. Y. Ko, H.
Masamune, and K. B. Sharpless, J. Am. Chem. Soc., 109, 5765
(
(
1987); Z.-M. Wang and K. B. Sharpless, Synlett, 1993, 603; P. J.
Walsh and K. B. Sharpless, Synlett, 1993, 605; H. Becker and K. B.
Sharpless, Angew. Chem., Int. Ed. Engl., 35, 448 (1996).
4
5
Biological methods: H. Ohta and H. Tetsukawa, Agric. Biol. Chem.,
4
5, 1895 (1981); T. Itoh, H. Ohara, Y. Takagi, N. Kanda, and K.
Uneyama, Tetrahedron Lett., 34, 4215 (1993).
Chemical methods: D. S. La, J. B. Alexander, D. R. Cefalo, D. D.
Graf, A. H. Hoveyda, and R. R. Schrock, J. Am. Chem. Soc., 120,
9
720 (1998).
Chemical methods: P. I. Dosa and G. C. Fu, J. Am. Chem. Soc., 120,
45 (1998); M. Nakamura, A. Hirai, M. Sogi, and E. Nakamura, J.
4
Am. Chem. Soc., 120, 5846 (1998); D. J. Ramon and M. Yus,
Tetrahedron Lett., 39, 1239 (1998); D. A. Evans, D. W. C.
MacMillan, and K. R. Campos, J. Am. Chem. Soc., 119, 10859
(
1997).
6
7
8
Chemical methods: H. Paulsen, C. Graeve, and D. Hoppe, Synthesis,
1
996, 141; C. Derwing and D. Hoppe, Synthesis, 1996, 149.
A review for chemical and biological synthesis of chiral epoxides: P.
Besse and H. Veschambre, Tetrahedron, 50, 8885 (1994).
Recent reviews on biological methods: E. Schoffers, A.
Golebiowski, and C. R. Johnson, Terahedron, 52, 3769 (1996); F.
Theil, Chem. Rev., 1995, 2203; H. Stecher and K. Faber, Synthesis,
butyldiphenylsiloxy-2-methylbutane-1,2-diol acetonide (18),
which were identified with those derived from known (R)-(–)-
1
997, 1; T. Hudlicky, D. Gonzalez, and D. T. Gibson, Aldrichimica
Acta, 32, 35 (1999).
17
atrolactic acid (19) and (S)-(+)-citramalic acid (20), respectively
Scheme 2). These facts showed that also in secondary benzylic
9
Recent reviews on chemical methods: M. Wills and H. Tye, J. Chem.
Soc., Perkin Trans. 1, 1999, 1109; E. J. Corey and A. Guzman-
Perez, Angew. Chem., Int. Ed. Engl., 37, 388 (1998); H. C. Kolb, M.
S. VanNieuwenhze, and K. B. Sharpless, Chem. Rev., 94, 2483
(1994); R. Noyori and T. Ohkuma, Pure Appl. Chem., 71, 1493
(
and non-allylic alcohol systems, the carbene insertion reaction
proceeded with complete retention of configuration of the chiral
center of the starting alcohols. In addition to acetonide, such pro-
tecting groups of alcohol as methyl (7a) and tert-butyldimethylsi-
lyl (TBDMS) ethers (7b) are compatible with the reaction condi-
tions, although the corresponding methoxymethyl (MOM) ether
(
1999).
1
0
J. A. Landgrebe and D. E. Turman, J. Am. Chem. Soc., 90, 6256
(1968).
1
1
2
D. Seyferth and Y. M. Cheng, J. Am. Chem. Soc., 95, 6763 (1973).
K. Steinbeck and J. Klein, J. Chem. Res. (S), 1980, 94; J. Chem. Res.
1
(M), 1980, 1150; K. Steinbeck , Tetrahedron Lett., 21, 2149 (1980).
(
7c) and acetate (7d) appeared to be poor substrates to yield little
13 A. Oku, T. Harada, K. Hattori, Y. Nozaki, and Y. Yamaura, J. Org.
Chem., 53, 3089 (1988); T. Harada, Y. Nozaki, and A. Oku,
Tetrahedron Lett., 24, 5665 (1983); T. Harada, E. Akiba, and A.
Oku, J. Am. Chem. Soc., 105, 2771 (1983); T. Harada and A. Oku, J.
Am. Chem. Soc., 103, 5965 (1981).
or no desired products with recovery of large amounts of the start-
ing material 7c and the hydrolyzed product, α-phenethylalcohol,
respectively. The α-methine C–H bond of protected non-allylic
alcohols (9–15) was transformed highly regioselectively to the
corresponding dichloromethyl group albeit in moderate yields.
A high level of kinetic isotope effect (k /k = 3.4) observed
in this carbene insertion reaction of mono-deuterated benzyl-
methyl ether PhCH(D)OCH , and the perfect retention of configu-
ration of the starting secondary alcohols observed strongly suggest
the reaction mechanism associated with three membered transition
1
4
C. Morpain, B. Nasser, B. Laude, and N. Latruffe, J. Org. Prep.
Proced. Intern., 22, 540 (1990); F. W. Eastwood, K. J. Harrington, J.
S. Josan, and J. L. Pura, Tetrahedron Lett., 11, 5223 (1970).
1
5
Crystal data for 4 : space group P2 2 2 (#19), with a=13.886(2),
1
1 1
H
D
3
3
b=16.231(2), c=7.970(1)Å, V=1796.3(4)Å , Z=4, D =1.457g/cm ,
c
R=0.047, R =0.059 for 1495 reflections with 1 > 2σ (l) of 1881
w
unique ones (2θ<136.5°) measured on a Rigaku RAXIS-RAPID
imaging plate using Cu Kα radiation. The absolute configuration of
the molecule (4) was determined based on the Flack’s parameter,
3
0
.07(5) [∆f" = 0.702 for Cl], and confirmed by the Bijvoet inequality
state involving a free carbene of singlet state and the C –H
relationship. Comparisons were made for the reflections of which
calculated Bijvoet differences larger than σ values: 32 of 35 Bijvoet
pairs showed the correct trend.
α
bond.11
In conclusion, a simple operation of protected optically active
16 Enantiomeric purity of all the dichloromethylated compounds
obtained in this reaction of optically pure alcohol derivatives used
was measured to be more than 98% ee in comparison with the corre-
sponding racemates by HPLC using Daicel CHIRALCEL OD and
OJ eluted with a mixed solvent of hexane/2-propanol (500/1).
secondary alcohols in CHCl /50% NaOH in the presence of PTC
3
offers a facile and practical method for synthesis of optically
active tertiary alcohol building blocks. Synthetic manipulations of
the α-dichloromethylated tertiary alcohol derivatives directed to
optically active natural products are in progress in this laboratory.
17
Optically pure (R)-(–)-atrolactic acid (19) and (S)-(+)-citramalic acid
20) were purchased from Lancaster Synth. Ltd. and Aldrich Chem.
Co. Inc., respectively.
(