Organic synthesis
Kamil Paruch
Masaryk University, Brno
Enols & enolates: formation, structure, reactivity
C-C bonds
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Knoevenagel condensations
Tetrahedron Lett. 1986, 27, 1767.
J. Chem. Soc. 1926, 1570.
• enolate attacks carbonyl C, subsequent elimination of H2O
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Org. Synth. Coll. Vol. 3, 1955, 165.
Helv. Chim. Acta 1950, 33, 2215.
Robinson annulation
• Michael addition + aldol condensation
• both ketones can be prepared non-racemic by proline-catalyzed Robinson annulation4
Henry reaction
J. Org. Chem. 1950, 15, 8.
Helv. Chim. Acta 1988, 71, 1.
Nef reaction
modern version: 1. LDA 2. MoOPh
or TiCl3
or 1. KOH 2. KMnO4
J. Org. Chem. 1985, 501, 4971.
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Claisen condensation
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Dieckmann condensation
• intramolecular version of Claisen condensation
J. Am. Chem. Soc. 1976, 98, 1583.
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Thorpe reaction
• „enolates“ of nitriles
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Mannich reaction
base-catalyzed
acid-catalyzed
• frequently used in assembly of cyclic N-containing systems
typically more reactive CO
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Chem. Pharm. Bull. 1991, 39, 1349.
Eschenmoser‘s salt
note: only 6% yield with HCHO + Me2NH
(sterically hindered substrate)
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Mannich reaction is frequently used in assembly of cyclic N-containing systems
J. Chem. Soc. 1917, 762.
“biomimetic approach”
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J. Am. Chem. Soc. 1996, 118, 9202.
Org. Lett. 2000, 2, 993.
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Strecker reaction
J. Org. Chem. 1987, 52, 4477.
• synthesis of amino acids
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Aldol reaction: 2 new stereogenic centers can be created
• stereochemistry of products depends on the configuration of the starting enolates
Z vs. E enolate
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GEOMETRY OF ENOLATES - IRELAND MODEL
small R1
E
large R1
Z
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GEOMETRY OF ENOLATES - EFFECT OF BASE
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• enolates often form clusters
J. Am. Chem. Soc. 1986, 108, 462.
Helv. Chim. Acta 1981, 64, 2617.17
SELECTIVE FORMATION OF E OR Z ENOL BORINATES
R2BCl with large alkyls (e.g. cyclohexyl) + small base (Et3N) -> E enolates
R2BOTf with small alkyls (e.g. n-butyl) + large base (DIPEA) -> Z enolates18
Aldol reaction: 2 new stereogenic centers can be created
• sterochemistry of products depends on the configuration of the starting enolates
• stereochemistry can also depend on R3
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Felkin-Anh
Nu attacks C=O: 107° angle
• stereoselective reactions with large Nu
Nucleophilic attack on C=O
R2 = H,
R1, R3 achiral
R2 = H,
R1 achiral
R3 chiral
racemic mixture
mixture of diastereomers
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Zimmerman-Traxler
Z enolate
E enolate
• cyclic transition state
R2 is not H, R3 achiral
Aldol reaction: 2 new stereogenic centers can be created
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R2 is not H, R3 chiral
Aldol reaction: 2 new stereogenic centers can be created
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com. available
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Aldol reaction: asymmetric induction
R3 contains stereogenic center: typically, conditions can be adjusted so that the syn- or anti- product is predominant
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