Synthesis of Homoallylic Amines Aza-Sakurai

HomoallyUc amines are useful intermediates in the synthesis of biologically active compounds such as statin, conine, lobeline, sedamine, SKF-1(K)330-A, epothilone, p-lactams, p-amino acids, and many natural products. The synthesis of those interesting precursors is also possible starting from an imine instead of a carbonyl compound, through this kind of reactivity, known in this case as aza-Sakurai reaction [94, 95]. Its multicomponent version involves the in situ formation of that imine, and few recent examples are shown here. 

They envisioned this synthesis as starting from alkyl chloroformate (CbzCl) and 1,1,1,3,3,3-hexamethyldisi-lazane (HMDS) that provided easily Af-silylcarbamate 

SCHEME 12.18 Br0nsted acid-catalyzed three-component Sakurai reaction using either silyl ether path I) or the corresponding alcohol (path II). 

SCHEME 12.19 Four-component aza-Sakurai reaction catalyzed by FeSO -7HjO. 

Since from the beginning two electrophiles (carbonyl compound and alkyl chloroformate) and two nucleophiles (HMDS and allyltrimethylsilane) are present in the media, the challenge of this reaction is to drive it for the previously described pathway. Side reactions such as allylation of the carbonyl compound and reaction between electrophihc alkyl chloroformate and nucleophilic allyltrimethylsilane were efficiently avoided using the proper Lewis acid as catalyst, being in this case the inexpensive FeSO -TH O. 

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