The Stereochemistry of Nucleophilic Addition. V. The Reformatsky Reaction of 2-Phenylpropanal with Methyl α-Bromopropionate

The Reformatsky reaction of 2-phenylpropanal (I) with methyl α-bromopropionate gave the diastereomeric methyl 3-hydroxy-2-methyl-4-phenylvalerates, IIa, IIb, IIe, and IId, in a 5 : 24 : 16 : 55 ratio. The configurations of these β-hydroxy esters were assigned by the following experiments. The reduction of IIa–IId with LiAlH4 gave the corresponding diols, IIIa–IIId, which were then converted to the monotosylates, IVa–IVd. The further reduction of IVa or IVc and IVb or IVd with LiAlH4 gave the epimeric 2-methyl-4-phenyl-3-pentanols, V and VI respectively. Since V and VI were also obtained as minor and major products (20 : 80 ratio) of the Grignard reaction of I with isopropylmagnesium iodide, the configurations of the C-3 and C-4 positions in IIa–IId were assigned. The Wittig reaction of I with carbomethoxyethylidenetriphenylphosphorane gave methyl 2-methyl-4-phenyl-2-cis-pentenoate (VII) and its trans-isomer (VIII), which were then reduced to the corresponding alcohols, IX and X respectively. The cis-hydration of IX gave IIIc and IIId, while a similar treatment of X gave IIIa and IIIb. From this experiments, the relative configurations from the C-2 position to the C-3 position in IIa–IId were also assigned. These configurational assignments of IIa–IId were further confirmed by the ozonization of IIa–IId.