Pinacol Couplings of Imines and Their Equivalents

Representative procedure. To a solution of oxime 17 (1 equiv) and t-BuOH (2.5 equiv) in THF was added dropwise Sml2 (3 equiv) in anhydrous degassed THF under an argon atmosphere at -78 °C. The solvent was then evaporated at reduced pressure. The resulting residue was taken up in Et20 and filtered through a pad of Celite. The filtrate was concentrated in vacuo and the crude product was purified by column chromatography (EtOAc-hexanes eluent). 

As oximes and hydrazones are not good electron acceptors, the mechanism for these reactions most likely involves an intermediate ketyl radical anion, which adds to the C=N double bond. A three-electron-two-orbital interaction involving the nitrogen-centred radical with the lone pair of the adjacent 

An impressive application of an aldehyde-oxime coupling was reported by Nicolaou in their studies on the total synthesis of the complex natural product diazonamide A (see Chapter 7, Section 7.4).29,30 Naito31 and Skrydstrup32 have reported impressive applications of the heteropinacol cyclisation for the stereoselective synthesis of the azepine ring of the PKC-inhibitor balanol (see Chapter 7, Section 7.4). 

Representative procedure. Sml2 (1.3 equiv) in anhydrous degassed THF was cooled to -78 °C under nitrogen and a solution of t-BuOH (1.3 equiv) and aldehyde (1 equiv) in dry THF was added dropwise. A - /v-Butylsulfinyliminc (0.7 equiv) in dry THF was then added dropwise. The reaction was quenched with aqueous saturated Na2S203 and extracted into EtOAc, then dried (Na2S04) and concentrated in vacuo. The crude product was purified by column chromatography. 

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