Download Solid phase reactions II

Solid phase reactions II
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Reduction, oxidation, formation of
carbonyl compounds and
derivates thereof
Formation of carbonyl compounds
Formation of carbonyl compounds
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Ozonolysis
Hydroformylation
Reduction of carboxylic acids (Weinreb amide)
Oxidation of alcohols
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Reduction of carboxylic acids
Oxidation of polymer-bound alcohols to
aldehydes/ketones
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Swern-oxidation
Dess-Martin-periodinane
TPAP (Pr4N+RuO4-)
Cr-reagents (PCC,...)
IBX (o-Iodoxybenzoic acid)
SO3/pyridine
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Oxidation of a secondary alcohol with TPAP
Oxidation of carbonyl compounds
Oxidation of polymer-bound carbonyl compounds
Oxidation of alcohols and carbonyl groups to
carboxylic acids:
„ Cr-reagents (PDC, Jones Oxidation)
„ KMnO4
Oxidation of carbonyl compounds to carboxylic
acids:
„ NaClO2
Oxidation sequence in the synthesis of
sarcodictyins
Reduction of carbonyl compounds
Reduction of polymer-bound carbonyl compounds
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reduction to alcohol (NaBH4, LiBH4,...)
diastereoselective reductions
(Evans-Tishchenko SmI2, Zn(BH4)2,...)
reductive amination (NaCNBH3,
NaBH(OAc)3, Me4NBH(OAc)3)
Reductive amination with Me4NBH(OAc)3
Carbonylderivates
Formation of acid halogenides
problem:
SOCl2 or POCl3 are incompartible with acid-sensitive
linkers as well as with the resin itself
solutions:
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PPh3/CCl4 combination (Apple)
oxalyl chloride
formation of acid fluorides using cyanuric fluoride
Formation of acid flourides
Esterification of carboxylic acids
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lack of methods for acide chloride formation
mainly two procedures
Steglich:
DIC/DMAP
Yamaguchi: TCBC (2,4,6-trichlorobenzoylchloride)
Esterhydrolysis:
„ addition of solvents with better swelling properties
Yamaguchi esterification
Reduction of esters using DIBALH
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in solution:
ability to stop the reaction at the aldehyde
oxidation state
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solid phase:
stopping at the aldehyde oxidation state not
possible, as excess of the reagent is needed
to drive the reaction to completion
Formation of amides
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introduction of a suitable leaving group instead of the OH
group prior to the reaction with an amine
two principle ways:
(1) replacement of the OH group (e.g. acid
halogenides)
(2) transformation into a suitalbe leaving group
(e.g. active esters, anhydrides)
best conditions highly dependent on the steric and
electronic nature of amine and carboxylic acid
Different coupling methods
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Carbodiimide-mediated couplings (DIC or DCC)
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Carbodiimide/HOBt (activating base: NMM or DIEA)
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HBTU or TBTU (activating base: NMM or DIEA)
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HATU or HOAt/DIC (activating base: NMM or DIEA)
Literature
Bannwarth W. and Felder E. (eds.): Combinatorial
chemistry:A Practical Approach, Wiley-VCH, Weinheim,
2000
Jung G. (ed.): Combinatorial chemistry, Synthesis,Analysis,
Screening, Wiley-VCH, Weinheim 1999
Nicolaou K., Hanko R., Hartig W. (eds.): Handbook of
combinatorial chemistry, Wiley-VCH, Weinheim 2002