Synthesis of Zaragozic Acid C

Structure of Zaragozic Acid C

C40H50O14

Principal investigator	David A. Evans
Publication year	1994
Synthesis type	Total
Number of steps	29 (3 parts)
References	Tetrahedron Lett. 1993, 34, 8403. J. Am. Chem. Soc. 1994, 116, 12111.

Part 1 of 3

intermediate structure

+

intermediate structure

Et3N, n-Bu2BOTf

CH2Cl2

-78 to -40 °C, 2.5 h, 96%

See the Evans Asymmetric Aldol Addition

intermediate structure

2,6-Lutidine, TBSOTf

CH2Cl2

0 °C, 60 min

intermediate structure

LiBH4

MeOH, THF

0 °C, 3.5 h

intermediate structure

(COCl)2, DMSO, Et3N

CH2Cl2

-78 to 0 °C, 90 min, 92% (3 steps)

See the Swern Oxidation

intermediate structure

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Part 2 of 3

intermediate structure

AllylMgBr

THF

0 °C, 93%

See the Weinreb Ketone Synthesis

intermediate structure

NaBH4, Et2BOMe

AcOH, MeOH

85%

See the Narasaka-Prasad Reduction

intermediate structure

Pyr.TsOH, 2,2-Dimethoxypropane

PhH

98%

intermediate structure

Li

NH3, THF

-60 °C, 100%

See the Birch Reduction

intermediate structure

""This iodide was readily prepared from intermediates previously reported by us""

intermediate structure

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Part 3 of 3

intermediate structure

TsOH, Cyclopentanone dimethyl acetal

PhH

65 °C, 12 h, 85%

intermediate structure

TMS2NLi
TMSCl

THF

-78 to 0 °C, 60 min, 97%

intermediate structure

+

intermediate structure

i-PrOTiCl3

CH2Cl2

-78 to -40 °C, 4.5 h, 76%

See the Mukaiyama Aldol Addition

intermediate structure

Dess-Martin Periodinane, Pyr

CH2Cl2

RT, 8 h, 94%

See the Dess-Martin Oxidation

intermediate structure

VinylMgBr

CH2Cl2, THF

-78 °C, 10 h, 76%

See the Grignard Reaction

intermediate structure

NMO, OsO4

H2O, t-BuOH, THF

40 h

See the Upjohn Dihydroxylation

intermediate structure

Pb(OAc)4

PhH

20 min

See the Criegee Reaction

intermediate structure

NMO, n-Pr4N+ RuO4-

4 Å MS

CH2Cl2

RT, 5 h, 84% (3 steps)

See the Ley-Griffith Oxidation

intermediate structure

O3 , Pyr
Me2S

CH2Cl2

-78 °C to RT, 4 h

intermediate structure

NaClO2, 2-Methyl-2-butene, NaH2PO4

t-BuOH

3.5 h

See the Pinnick-Lindgren Oxidation

intermediate structure

N,N'-diisopropyl-O-tert-butylisourea

CH2Cl2

24 h, 91% (3 steps)

intermediate structure

+

intermediate structure

t-BuLi

Et2O, Hexane(s)

-78 °C, 20 min, 73%

intermediate structure

DDQ

CH2Cl2

60 min

intermediate structure

Ac2O, DMAP

PhH, Pyr

90% (2 steps)

intermediate structure

H2O

CH2Cl2, CF3CO2H

intermediate structure

N,N'-diisopropyl-O-tert-butylisourea

CH2Cl2

24 h, 52% (2 steps)

intermediate structure

H2, Pd/C

50 atm

AcOH, MeOH

20 h, 96%

intermediate structure

+

intermediate structure

DCC, DMAP

CH2Cl2

36 h, 82%

See the Steglich Esterification

intermediate structure

n-Bu4N+ F-

THF

0 °C, 15 min, 99%

intermediate structure

CF3CO2H

CH2Cl2

24 h, 99%

intermediate structure

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