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DOI: 10.1055/s-0029-1218562
Modified Cinchona Alkaloid-Zinc Complex Catalysts: Enantioselective Monoacetylation of Glycerol Derivatives with Acetic Anhydride
Publikationsverlauf
Publikationsdatum:
10. Dezember 2009 (online)

Abstract
Enantioselective monoacetylation of σ-symmetric glycerol derivatives with acetic anhydride catalyzed by modified cinchona alkaloid-zinc complexes was achieved in up to 86% ee at 5 mol% catalyst loading.
Key words
cinchona alkaloid - zinc complex - asymmetric synthesis - glycerol - acetylation
- For reviews on desymmetrization of diols, see:
-
1a
Mori K. Pure Appl. Chem. 1994, 66: 1991 -
1b
Periasamy M. Aldrichimica Acta 2000, 35: 89 -
1c
Rendler S.Oestreich M. Angew. Chem. Int. Ed. 2008, 47: 248 -
2a
Sano S.Nakao M.Takeyasu M.Honjo T.Nagao Y. Lett. Org. Chem. 2006, 3: 764 -
2b
Sano S.Nakao M.Takeyasu M.Yamamoto C.Kitaike S.Yoshioka Y.Nagao Y. Open Org. Chem. J. 2009, 3: 22 - 3
Chênevert R.Courchesne G.Pelchat N. Bioorg. Med. Chem. 2006, 14: 5389 -
4a
Jung B.Kang SH. Proc. Natl. Acad. Sci. U.S.A. 2007, 104: 1471 -
4b
Jung B.Hong MS.Kang SH. Angew. Chem. Int. Ed. 2007, 46: 2616 -
4c
Kim HC.Kang SH. Angew. Chem. Int. Ed. 2009, 48: 1827 - 5
Honjo T.Nakao M.Sano S.Shiro M.Yamaguchi K.Sei Y.Nagao Y. Org. Lett. 2007, 9: 509 -
6a
Lipscomb WN.Sträter N. Chem. Rev. 1996, 96: 2375 -
6b
Auld DS. Biometals 2009, 22: 141 - 7
Ishihara K.Sakakura A.Hatano M. Synlett 2007, 686 - For recent reviews on cinchona alkaloids in asymmetric synthesis, see:
-
8a
Kacprzak K.Gawroński J. Synthesis 2001, 961 -
8b
Chen Y.McDaid P.Deng L. Chem. Rev. 2003, 103: 2965 -
8c
Hoffmann HMR.Frackenpohl J. Eur. J. Org. Chem. 2004, 4293 -
8d
O’Donnell MJ. Acc. Chem. Res. 2004, 37: 506 -
8e
Lygo B.Andrews BI. Acc. Chem. Res. 2004, 37: 518 -
8f
Ooi T.Maruoka K. Acc. Chem. Res. 2004, 37: 526 -
8g
Tian S.-K.Chen Y.Hang J.Tang L.McDaid P.Deng L. Acc. Chem. Res. 2004, 37: 621 -
8h
Dalaigh CO. Synlett 2005, 875 -
8i
Marcelli T.van Maarseveen JH.Hiemstra H. Angew. Chem. Int. Ed. 2006, 45: 7496 -
8j
Shibata N.Ishimaru T.Nakamura S.Toru T. J. Fluorine Chem. 2007, 128: 469 -
8k
Blaser H.-U.Studer M. Acc. Chem. Res. 2007, 40: 1348 -
8l
Ting A.Schaus SE. Eur. J. Org. Chem. 2007, 5797 -
8m
Gaunt MJ.Johansson CCC. Chem. Rev. 2007, 107: 5596 -
8n
Chen Y.-C. Synlett 2008, 1919 -
8o
Connon SJ. Synlett 2009, 354 -
8p
Xu L.-W.Luo J.Lu Y. Chem. Commun. 2009, 1807 -
8q
Wu L.-Y.Bencivenni G.Mancinelli M.Mazzanti A.Bartoli G.Melchiorre P. Angew. Chem. Int. Ed. 2009, 48: 7196 - 10
Oh SH.Rho HS.Lee JW.Lee JE.Youk SH.Chin J.Song CE. Angew. Chem. Int. Ed. 2008, 47: 7872 - 12
Forbes DC.Ene DG.Doyle MP. Synthesis 1998, 879 - 13
Green TW.Wuts PGM. In Protective Groups in Organic Synthesis 3rd ed.: John Wiley and Sons; New York: 1999. p.86 - 16
Wirz B.Barner R.Hübscher J. J. Org. Chem. 1993, 58: 3980
References and Notes
The ¹H NMR spectra of a mixture of chiral ligand 1 and Et2Zn were complicated by multiple signals arising from rotamers of 1. In the case of our previous results, the structure of chiral sulfonamide-Zn complex (2:1) was determined by X-ray crystallographic analysis.5 However, attempts to crystallize the Zn complex of chiral ligand 1 were unsuccessful.
11The authors reported the experimental results at the 126th annual meeting of the Pharmaceutical Society of Japan, Sendai, Japan, 2006, abstract No. 4, pp. 137.
14
General Experimental
Procedure for a Modified Cinchona Alkaloid-Zinc Complex
Catalyzed Desymmetrization of Glycerol Derivatives
To
a solution of modified cinchona alkaloid 1 (6.0
mg, 0.01 mmol) in Et2O (4 mL) was added Et2Zn
(1.0 M in n-hexane, 10 µL, 0.01
mmol) at r.t. The mixture was stirred at r.t. for 10 min, and diol 9a (51.3 mg, 0.2 mmol) and Ac2O
(28 µL, 0.3 mmol) were then added to the solution at 0 ˚C.
After stirring at 0 ˚C for 20 h, the reaction mixture was
treated with sat. aq NaHCO3 (5 mL) followed by extraction
with CHCl3 (75 mL). The extract was dried over anhyd
MgSO4, filtered, and concentrated in vacuo. The oily
residue was purified by silica gel column chromatography (EtOAc-n-hexane, 1:1) to afford 9aa (46.3
mg, 78% yield, 86% ee) as a colorless oil.
The
ee (%) of (S)-9aa (Scheme
[²]
) was determined on a Chiralpak
IA, n-hexane-EtOH (3:1), flow
rate: 1 mL/min, detection: 254 nm]. The retention
times were 9.4 min [minor product, (R)-9aa] and 12.2 min [major
product, (S)-9aa], respectively.
The absolute configuration of (S)-9aa was explicitly determined by its chemical
conversion to acetonide (S)-15 {[α]D
²0 -3.1
(c 1.01, EtOH), lit.¹6 (R)-15 [α]D +5.8
(c 1.00, EtOH)}.

Scheme 2
Spectroscopic
Data of 9aa-ea (Table 4)
Compound 9aa (R = Me):
colorless oil. ¹H NMR (400 MHz, CDCl3): δ = 1.28
(3 H, s), 2.10 (3 H, s), 2.15 (1 H, s), 3.56-3.59 (2 H,
m), 3.79 (6 H, s), 4.17 (1 H, d, J = 11.7
Hz), 4.24 (1 H, d, J = 11.7
Hz), 4.48 (2 H, s), 6.38 (1 H, t, J = 2.2
Hz), 6.49 (2 H, d, J = 2.2
Hz). ¹³C NMR (75 MHz, CDCl3): δ = 17.5,
20.9, 55.3, 64.6, 65.4, 65.7, 76.8, 99.4, 105.2, 141.1, 160.9, 171.1.
IR (neat): 3471, 2939, 2843, 1738, 1599, 1464, 1244, 1205, 1155,
1053 cm-¹. ESI-MS: m/z calcd
for C15H22NaO6: 321.1314; found:
321.1324 [M+ + Na].
Compound 9ba (R = Et):
colorless oil. ¹H NMR (400 MHz, CDCl3): δ = 0.96
(3 H, t, J = 7.7
Hz), 1.60-1.72 (2 H, m), 2.10 (3 H, s), 2.21 (1 H, s),
3.57 (1 H, d, J = 12.0
Hz), 3.62 (1 H, d, J = 12.0
Hz), 3.79 (6 H, s), 4.20 (1 H, d, J = 11.7 Hz),
4.25 (1 H, d, J = 11.7
Hz), 4.45 (2 H, s), 6.37 (1 H, t, J = 2.2
Hz), 6.51 (2 H, d, J = 2.2
Hz). ¹³C NMR (75 MHz, CDCl3): δ = 7.0,
20.9, 22.6, 55.3, 62.8, 63.6, 63.9, 78.6, 99.4, 105.2, 141.0, 160.9,
171.2. IR (neat): 3481, 2968, 1741, 1599, 1462, 1238, 1205, 1155,
1063 cm-¹. ESI-MS: m/z calcd
for C16H24NaO6: 335.1471; found:
335.1471 [M+ + Na].
Compound 9ca (R = i-Pr): colorless oil. ¹H
NMR (400 MHz, CDCl3): δ = 1.01 (3 H,
d, J = 3.2
Hz), 1.03 (3 H, d, J = 3.2 Hz),
2.07-2.10 (4 H, m), 2.17-2.25 (1 H, m), 3.73-3.76
(2 H, m), 3.79 (6 H, s), 4.34 (1 H, d, J = 12.2
Hz), 4.36 (1 H, d, J = 12.2
Hz), 4.52 (1 H, d, J = 11.5
Hz), 4.54 (1 H, d, J = 11.5
Hz), 6.38 (1 H, t, J = 2.2
Hz), 6.52 (2 H, d, J = 2.2
Hz). ¹³C NMR (75 MHz, CDCl3): δ = 17.06,
17.13, 21.0, 30.1, 55.3, 62.6, 64.5, 64.6, 79.7, 99.3, 105.0, 141.4,
160.9, 171.0. IR (neat): 3483, 2964, 1741, 1599, 1238, 1205, 1155,
1055 cm-¹. ESI-MS: m/z calcd
for C17H26NaO6: 349.1627; found: 349.1597 [M+ + Na].
Compound 9da (R = CH2=CHCH2):
colorless oil. ¹H NMR (400 MHz, CDCl3): δ = 2.10
(3 H, s), 2.21 (1 H, br s), 2.44 (2 H, d, J = 7.3
Hz), 3.60 (1 H, d, J = 12.0
Hz), 3.64 (1 H, d, J = 12.0
Hz), 3.78 (6 H, s), 4.21 (1 H, d, J = 12.0
Hz), 4.26 (1 H, d, J = 12.0
Hz), 4.52 (2 H, s), 5.14-5.20 (2 H, m), 5.81-5.92
(1 H, m), 6.38 (1 H, t, J = 2.2
Hz), 6.50 (2 H, d, J = 2.2 Hz). ¹³C
NMR (75 MHz, CDCl3): δ = 20.9, 35.2,
55.3, 63.2, 63.9, 64.3, 78.3, 99.4, 105.3, 118.9, 132.2, 140.9,
160.8, 171.1. IR (neat): 3483, 2939, 1741, 1599, 1464, 1238, 1205, 1155,
1055 cm-¹. ESI-MS: m/z calcd
for C17H24NaO6: 347.1471; found:
347.1494 [M+ + Na].
Compound 9ea (R = Ph):
colorless oil. ¹H NMR (400 MHz, CDCl3): δ = 2.06
(3 H, s), 2.22 (1 H, br s), 3.79 (6 H, s), 3.88-3.99 (2
H, m), 4.30 (1 H, d, J = 11.5
Hz), 4.35 (1 H, d, J = 11.5
Hz), 4.64 (2 H, s), 6.38 (1 H, t, J = 2.2
Hz), 6.50 (2 H, d, J = 2.2
Hz), 7.32-7.36 (1 H, m), 7.38-7.45 (4 H, m). ¹³C
NMR (75 MHz, CDCl3): δ = 20.9, 55.3,
65.0, 65.3, 65.5, 80.5, 99.4, 105.2, 126.7, 128.3, 128.7, 138.5,
140.7, 160.9, 170.9. IR (neat): 3481, 2939, 1741, 1599, 1462, 1238,
1205, 1155, 1053 cm-¹. ESI-MS: m/z calcd for C20H24NaO6: 383.1471;
found: 383.1466 [M+ + Na].