Stereochemistry 2-phenylpropanal

The addition of methylmagnesium iodide to 2-phenylpropanal is stereoselective in producing twice as much syn-3-phenyl-2-butanol as the anti isomer (entry 5). The stereoselective formation of a particular configuration at a new stereogenic center in a reaction of a chiral reactant is called asymmetric induction. This particular case is one in which the stereochemistry can be predicted on the basis of an empirical correlation called Cram s rule. The structural and mechanistic basis of Cramls rule will be discussed in Chapter 3. 

Starting with two chiral centres, there should, therefore, be four stereoisomers, and this is nicely exemplified by the natural alkaloid (-)-ephedrine, which is employed as a bronchodilator drug and decongestant. Ephedrine is (li ,25)-2-methylamino-l-phenylpropan-l-ol, so has the structure and stereochemistry shown. 

Solvent and temperature effects on the diastereoselective addition of n-BuLi to 2-phenylpropanal have been reassessed95 and the stereochemistry of addition of organolithium reagents to carbohydrate enones has been studied.96 No compelling evidence has been found to support the suggestion that addition of n-BuLi to benzoic acid might compete with formation of the lithium salt and thereby provide an alternative to the sequential route to PhCOBu".97... 

Diphenyl-1-propanol can be prepared by hydride reduction of 1,2-diphenyl-1-propanone or by addition of phenylmagnesium bromide to 2-phenylpropanal. Predict the stereochemistry of the major product in each case. 

Romanova [80] studied the effect of microwave irradiation on the direction and stereochemistry of the Rodionov reaction. Microwave irradiation of a mixture of equimolecular amounts of benzylammonium acetate 128, monoethyl malonate 130, and 2-phenylpropanal 127 resulted in the formation of yS-amino ester 132 in 38% yield and ethyl-4-phenyl-2-pentenoate 133 in 60% yield, exclusively as the trans isomer (Scheme 5.36). By contrast, thermal activation does not lead to forma-... 

The situation becomes a little more complex if the aldehyde contains a chiral centre, as in 2-phenylpropanal. In such cases, the aldol product formed contains three chiral centres and there are four possible diastereoisomers - two 2,3-syn and two 2,3-anti isomers (and their enantiomeric pairs, thereby totalling eight stereoisomers) (1.69). The relative stereochemistry of the substituents at C-2 and C-3 is controlled by the geometry of the enolate. The C-3,C-4 stereochemistry, on the other hand, depends on the direction of approach of the enolate and the carbonyl group to each other. This is illustrated in Scheme 1.70, for the reaction of 2-phenylpropanal with the trans-enolate of 2,6-dimethylphenyl propionate. 

The kinetics and stereochemistry of the acid-induced dissociation of O-protonated and O-methylated (5)-l-phenylpropan-2-ol and (5)-2-phenylpropan-l-ol have been investigated in the gas phase, and evidence has been provided " to support a mechanism that involves competing anchimeric assistance from all the groups adjacent to the reaction centre. An assessment of the neighbouring-group ability of the phenyl group... 

Specific, relatively simple glycosides to have been synthesised include t-butyl-i0-D-galactopyranoside tetra-acetate, the corresponding lactoside ° and 2-phenylpropan-l-yl p-H glucopyranuronoside. The stereochemistry within the aglycone is not noted in the abstract. 

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