Hillman

Apart from the thoroughly studied aqueous Diels-Alder reaction, a limited number of other transformations have been reported to benefit considerably from the use of water. These include the aldol condensation , the benzoin condensation , the Baylis-Hillman reaction (tertiary-amine catalysed coupling of aldehydes with acrylic acid derivatives) and pericyclic reactions like the 1,3-dipolar cycloaddition and the Qaisen rearrangement (see below). These reactions have one thing in common a negative volume of activation. This observation has tempted many authors to propose hydrophobic effects as primary cause of ftie observed rate enhancements. 

A. Cro2ier andj. R. Hillman, eds.. The Biosynthesis and Metabolism of Plant Hormones, Oxford University Press, Oxford, U.K., 1984. 

E. J. Duarte and L. W. Hillman, Dye Easer Princip/es, Academic Press, San Diego, Calif., 1990. 

BAYLIS - HILLMAN Vinyl alkylation Amine catalyzed converelon of acrylates to a-(hydroxyalkyl) acrylates or of vinyl ketones to a-(hydroxyalkyO vinyl ketones. 

K. Hillman, H. van Wyk, E. Milne, C.S. Stewart, and M.F. Fuller, in Symposium on Global Methane Flux, Abstracts, Society for General Microbiology, 1995, p. 24. 

S. Duncan, K. Hillman, A. Prosser and C.S. Stewart, unpublished data. 

An alkene activated by an electron-withdrawing group—often an acrylic ester 2 is used—can react with an aldehyde or ketone 1 in the presence of catalytic amounts of a tertiary amine, to yield an a-hydroxyalkylated product. This reaction, known as the Baylis-Hillman reaction, leads to the formation of useful multifunctional products, e.g. o -methylene-/3-hydroxy carbonyl compounds 3 with a chiral carbon center and various options for consecutive reactions. 

Together with a shift of the proton from the a-carbon to the alkoxide oxygen, the tertiary amine is eliminated from the addition product to yield the unsaturated product 3. Early examples of the Baylis-Hillman reaction posed the problem of low conversions and slow reaction kinetics, which could not be improved with the use of simple tertiary amines. The search for catalytically active substances led to more properly adjusted, often highly specific compounds, with shorter reaction times." Suitable catalysts are, for example, the nucleophilic, sterically less hindered bases diazabicyclo[2.2.2]octane (DABCO) 6, quinuclidin-3-one 7 and quinuclidin-3-ol (3-QDL) 8. The latter compound can stabilize the zwitterionic intermediate through hydrogen bonding. ... 

Apart from tertiary amines, the reaction may be catalyzed by phosphines, e.g. tri- -butylphosphine or by diethylaluminium iodide." When a chiral catalyst, such as quinuclidin-3-ol 8 is used in enantiomerically enriched form, an asymmetric Baylis-Hillman reaction is possible. In the reaction of ethyl vinyl ketone with an aromatic aldehyde in the presence of one enantiomer of a chiral 3-(hydroxybenzyl)-pyrrolizidine as base, the coupling product has been obtained in enantiomeric excess of up to 70%, e.g. 11 from 9 - -10 ... 

An intramolecular variant of the Baylis-Hillman reaction is also possible, and may be used for the construction of functionalized ring systems, e.g. a cyclopen-tene derivative such as 12. However, good yields have been achieved in only a few cases ... 

The Baylis-Hillman reaction is usually carried out under mild conditions (0°C or room temperature). The reaction time varies from a few minutes to even days. With the proper catalyst, good yields are possible. In the absence of an aldehyde or ketone as the electrophilic component, a dimerization of the activated alkene can take place under the influence of the catalyst, as also observed as a side reaction under the usual reaction conditions ... 

Conjugate dcLiicii of nkro ilkdnes to illyl Baylis-Hillman acetates in the pesence of NaOH (0.6 N in THF ves 2-alkylidene-4-nitro ketones with high sieteoselecdvity these are convened via the Nef teacdon into the conesponding 1,4-diketones fEq. 4.1... 

Hillman, J., et al., Integrated CVD Titanium and Titanium Nitride Process for Sub-0.5- im Metallization f Solid-State Technology, pp. 147-152 (July 1995)... 

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