Organic synthesis
Kamil Paruch
Masaryk University, Brno
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Kamil Paruch Organic Synthesis C4450reduction
McMurry reaction
• reductive coupling of carbonyl compounds on Ti
• can be used for preparation of sterically hindered olefins
• reaction can be stopped in the diol phase
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Kamil Paruch Organic Synthesis C4450
Tetrahedron 1986, 42, 2111..
J. Am. Chem. Soc. 1995, 117, 645.
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Kamil Paruch Organic Synthesis C4450
• imines can be also coupled
• unsymmetrical products (cross coupling): typically, one component in excess
J. Org. Chem. 1986, 51, 2361.
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Kamil Paruch Organic Synthesis C4450Wittig reaction
strong base (removal of H+)R3, R4 = alkyl, aryl nonstabilized ylide (Z)-alkene
weaker base (removal of H+)R3, R4 = electron acceptor stabilized ylide (E)-alkene
or
(Horner-Wadsworth-Emmons)
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Kamil Paruch Organic Synthesis C4450Wittig reaction
• Wittig reaction is often used in the synthesis of complex molecules
J. Am. Chem. Soc. 1969, 91, 5675.
Note: complexation with ZnCl2 will remove triphenylphosphine oxide, even from polar solvents: J. Org. Chem. 2017, 82, 9931.
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Kamil Paruch Organic Synthesis C4450Wittig reaction
(double) Wittig reaction can be used for construction of cyclic systems
Synthesis 1975, 765.
homologation of aldehydes
e.g.
J. Org. Chem. 1989, 54, 3831.
similarly: chloromethylenation
Tetrahedron Lett. 1980, 21, 4021.
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Kamil Paruch Organic Synthesis C4450
Wittig reaction
Seyferth-Gilbert homologation
Ohira-Bestmann alkynylation: frequently used for conversion of aldehydes to terminal alkynes
J. Am. Chem. Soc. 2001, 123, 8593.
alkynylation
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Kamil Paruch Organic Synthesis C4450Julia-Lythgoe olefination
Wittig:
Julia-Lythgoe:
Angew. Chem. Int. Ed. 2003, 42, 3943.
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Kamil Paruch Organic Synthesis C4450
Mitsunobu reaction
• nucleophilic substitution of OH under mild conditions
• SN2 -> inversion of configuration
J. Org. Chem. 1987, 52, 2960.
note: Ph3P + CBr4 (CCl4) : OH -> Br (Cl)
J. Am. Chem. Soc. 1982, 104, 5560.
NuH: pKa < 15
conversions of functional groups
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Kamil Paruch Organic Synthesis C4450conversions of functional groups
note: Et2NSF3 (DAST) : OH -> F
C=O -> CF2
Tetrahedron Lett. 1992, 33, 1509.
Tetrahedron Lett. 1988, 29, 5217.
note: NaI : Cl, Br, OMs, OTs -> I (Finkelstein reaction)
Org. Synth., Coll. Vol. 4, 1963, 84.
J. Am. Chem. Soc. 1980, 102, 6304.
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Kamil Paruch Organic Synthesis C4450conversions of functional groups
• Mitsunobu reaction: often method of choice for inversion of configuration
• also used for preparation of esters, lactones, amides, lactams and amines
J. Org. Chem. 1991, 56, 741.
J. Am. Chem. Soc. 1982, 104, 1774.
Tetrahedron Lett. 1992, 33, 3507.
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Kamil Paruch Organic Synthesis C4450conversions of functional groups
Angew. Chem. Int. Ed. Engl. 1999, 38, 240.
• generation of C-N bond: DPPA and phthalimide: common Nu sources of N
Org. Synth., Coll. Vol. 7, 1990, 501.
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Kamil Paruch Organic Synthesis C4450conversions of functional groups
J. Am. Chem. Soc. 2001, 123, 3239.
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Kamil Paruch Organic Synthesis C4450conversions of functional groups
esterification • conversion of carboxylic acids into derivatives with better leaving groups
• Mitsunobu rxn
• also frequently used for amides
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Kamil Paruch Organic Synthesis C4450conversions of functional groups
J. Org. Chem. 1982, 47, 1962.
J. Am. Chem. Soc. 1973, 95, 875.
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Kamil Paruch Organic Synthesis C4450
macrolactonization
• often applied in synthesis of (biologically active) macrolides
Yamaguchi macrolactonization
Chem. Lett. 1979, 1021.
conversions of functional groups
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Kamil Paruch Organic Synthesis C4450
iodolactonization
J. Am. Chem. Soc. 1969, 91, 5675.
J. Am. Chem. Soc. 1985, 107, 1448.
• anti attack on cyclic iodonium intermediate
conversions of functional groups
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Kamil Paruch Organic Synthesis C4450conversions of functional groups
hydroboration (and subsequent transformations)
• “anti-Markovnikov“ addition on double/triple bonds
• sterically hindered boranes: high regio- and stereoselectivity
• products of hydroboration can be converted into different derivatives
J. Am. Chem. Soc. 1992, 114, 6671.
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Kamil Paruch Organic Synthesis C4450conversions of functional groups
J. Am. Chem. Soc. 1979, 101, 96.
hydroboration of alkynes
terminal alkynes: E-alkenes
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Kamil Paruch Organic Synthesis C4450conversions of functional groups
J. Chem. Soc., Chem. Commun. 1971, 521.
J. Am. Chem. Soc. 1973, 95, 5786.
J. Am. Chem. Soc. 1964, 86, 3565.
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Kamil Paruch Organic Synthesis C4450conversions of functional groups
carbonylation of boranes
J. Am. Chem. Soc. 1969, 91, 1224.