unit 6 stereocontrolled aldol reactionsweb.mit.edu/5.512/www/lectures07/5.512 lecture...
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Massachusetts Institute of TechnologyOrganic Chemistry 5.512
April 25, 2007Prof. Rick L. Danheiser
Unit 6
Stereocontrolled Aldol Reactions
Overview of the Stereochemistry of the Aldol Reaction and Substrate Control
Reagent Control: Chiral Auxiliary Strategies
Reagent Control: Chiral Controller Strategies
Reagent Control: Chiral Lewis Acid Catalyzed Aldol Reactions
II. Chiral Auxiliary Strategies
R1OH
R2
O
Z234
The Aldol Retron
OBO
H
R
N
Me
Bu
Bu
O
O H
2,3-Syn Aldols
Evans OxazolidinoneBoron Enolates
Gage, J. R.; Evans, D. A.Org. Synth. 1990, 68, 83
Review"Asymmetric Aldol Reactions Using Boron Enolates"Cowden, C. J.; Paterson, I. Organic Reactions 1997, 51, 1
Alexsander Borodin
2,3-Anti Aldols
D. A. Evans et al.J. Am. Chem. Soc. 2002 124, 392
and Org. Lett. 2002, 4, 1127
(1) Evans Dones
(2) Oppolzer Sultams
NS
OO OSiR3
H
R
OH
Me
L.A.
(3) Masamune Esters
Review"Boron-Mediated Aldol Reaction of Carboxylic Esters"Abiko, A. Acc. Chem. Res. 2004, 37, 387see also Org. Synth. 2002, 79, 109 and 116
OOH OH O
OHOH
O
Myriaporone 4 Myriaporone 3
Tedanolide
Case Study
Total Synthesis of Myriaporones Fleming, K. N.; Taylor, R. E. Angew. Chem. Int. Ed. 2004, 43, 1728
OOH OH O
O
O
OH
OH
OMe O
O
HOCO2Me
NH
OCH2AnCl3C
95%
1) LiAlH470%
2) Swern90%
PMBOCHO
Li
THF, -78 °C
91%
PMBO
OH
SOCl2
70-80%
PMBO Cl
1) CsOAc2) K2CO3 MeOH
50%
PMBO OH
2 equiv IBXDMSO, rt
97%
N OOO
2 Bu2BOTf, Et3NCH2Cl2
1.5 TBDMSOTf2,6-lutidine
CH2Cl2
85%PMBO
t-BuMe2SiO
N O
O O
1) 5 LiBH4 Et2O2) 4 TBDMSCl Im, DMF
89%
2
93%
Cl3CCO2H
Tactics
OOH OH
OOH
O
OH
PMBO
t-BuMe2SiO
OSiR32) 5 NaIO4 aq MeOH
95%
1) cat OsO4 4 NMO aq t-BuOH
84%
PMBO
t-BuMe2SiO
N OOO1.5
1.5 Bu2BOTf Et3N, CH2Cl2
99%
PMBO
t-BuMe2SiO OH
N O
t-BuMe2SiO
O O
1) 5 LiBH4, Et2O2) 1.2 TBDMSCl cat DMAP Et3N, CH2Cl2
92%
CHO
OSit-BuMe2
PMBO
t-BuMe2SiO OH
t-BuMe2SiO OSit-BuMe2