Carey Organic Chemistry Chapter 15 Alcohols, Diols, and Thiols Slides
Axially Chiral Biaryl Diols Catalyze Highly ...ccc.chem.pitt.edu/wipf/Current...
Transcript of Axially Chiral Biaryl Diols Catalyze Highly ...ccc.chem.pitt.edu/wipf/Current...
David Arnold 5/6/06
Axially Chiral Biaryl Diols CatalyzeHighly Enantioselective Hetero-Diels-Alder Reactions Through
Hydrogen Bonding
Aditya K. Unni, Norito Takenaka, HisashiYamamoto, and Viresh H. Rawal
J. Am. Chem. Soc. 2005, 127, 1336-1337
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Background• [4+2] cycloaddition of
heterodienophiles withheterodienes.
B
C
D
A
E
F B
C
D
E
F
A
+
ON
N
N
N
O
N
SO
S
Se
N
S+ OO N
Heterodienophiles
ON N
S
N
N
N
N
N
O
N
S
O
O
S
S
N
N
O
S
O
Heterodienes
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HDA Reactions with Aldehydes andKetones
• Importance: Formation of oxygenbased heterocycles such as 5,6-dihydropyrans which are importantsynthetic units found in many naturalproducts.
• Problem: Only highly reactivealdehydes and ketones readilyundergo HDA reactions with electronrich butadienes.
• Past solutions: 1) High temperatures 2) High pressures (15-25 kbar) 3) Lewis acid activation
H H
O
H
O
Cl
Cl
Cl
O
OH
O
OH
O
O
CH3
OH
OH
O
O
OH
OH
CH3
H
H
CO2Me
Vineomycinone B2 methyl ester
J. Am. Chem. Soc. 1985, 107, 1285 - 1292
Top. Curr. Chem. 1997, 189, 1 - 107.
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On the Road To Milder Conditions
In 2000, Viresh Rawal discovered that
1-amino-3-siloxy-1,3-butadienes are easily prepared,stable and highly reactive towards unactivatedaldehydes at room temp. in CH2Cl2 to givedihydro-4-pyrone products, following N-acylationand subsequent β-elimination, in good yields.
1) Aromatic aldehyde reaction rates corresponded tothere respective carbonyl electrophilicities.
2) Primary aliphatic aldehydes reacted within 2-3 hrs.
3) Secondary aliphatic aldehydes reacted within 6-8hrs.
4) The tertiary aldehyde reacted in 71 hrs.
Org. Lett., 2000, 2, 3321 – 3323.
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H-Bond Rate Acceleration of HDA Reactions ofUnactivated Ketones: Viresh Rawal 2002
J. Am. Chem. Soc. 2002, 124, 9662-9663.
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Chiral-Alchol Catalysts: Viresh Rawal2003
TBSO
N
H
O
O
TBSO
N
O
O+(R,R)-1-napthyl TADDOL
Toluene, -78 oC
CH3COCl
CH2Cl2/toluene
-78 oC, 15 min 70 %
S-enantiomer >99:1
OH
OH
Ar Ar
ArAr
O
O
Ar =
Chiral Catalyst
• Novel example of a hydrogen bonding chiralcatalyst, catalyzing an HDA reaction.
• Good yields and enantioselectivities
• Uncatalyzed HDA reaction does not proceed intoluene under identical conditions.
Nature 2003, 424, 146.
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A Natural Extension: Axially Chiral BiarylDiols: Viresh Rawal and Hisashi Yamamoto
2005
Synthesis of Axially Chiral BAMOLs
OH
OH
CO2Me
CO2Me
OH
ArAr
OH
ArAr
1. Tf2O, Pyridine
CH2Cl2, 0-20 oC
2. Pd(OAc)2, dppp, iPr2NEt
CO (1.5 atm), MeOH, DMSO, 80 oC, 48-72 h
ArLi, THF
-78 -> -10 oC
J. Am. Chem. Soc. 2005, 127, 1336-1337
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A Natural Extension Continued…TBSO
N
H
O
R
O
O R
+
1. 0.2 equliv. 3, toluene -40 or -80 oC
2. AcCl, CH2Cl2-toluene
-78 oC, 30 min
OH
ArAr
OH
ArAr
3a Ar = 4-F-3,5-Me2C6H2
3b Ar = 4-F-3,5-Et2C6H2
•Straight-chain aliphatic aldehydes:good yields excellent ee’s
•Branch-chain aldehydes: lower ee’s
•Lewis basic heteroatoms are welltolerated
•Electron rich and electron pooraromatic aldehydes give comparableee’s.
J. Am. Chem. Soc. 2005, 127, 1336-1337
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Crystal Structure of the Inclusion Complex of2,2’-bis-(diphenylhydroxymethyl)binaphthylene
and benzaldehyde
• 1:1 complex
• Intramolecular hydrogen bondbetween hydroxyls
• Intermolecular hydrogen bond tocarbonyl of benzaldehyde
• Carbonyl activation through asingle-point hydrogen bond
J. Am. Chem. Soc. 2005, 127, 1336-1337
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Conclusion• The use of hydrogen bonding solvents and chiral
hydrogen bonding catalysts as carbonyl activators hasproved to be an efficient method for both acceleratingthe hetero Diels-Alder reaction and controlling thestereochemical outcome.
• Chiral alcohol catalysis offers a potentially veryuseful alternative to traditional metal based Lewisacid catalysis and may possibly be extendedsuccessfully to many other asymmetric reactionsrequiring carbonyl activation.
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