Gold-catalyzed bis-cyclization of 1,2-diol- or acetonide-tethered alkynes. Synthesis of β-lactam-bridged acetals: a combined experimental and theoretical study

TETRAHEDRON

卷:68

Article

Alcaide, Benito¹  Almendros, Pedro²  Carrascosa, Rocio¹  Lopez, Ramon³  Menendez, Maria I.³ 

[1] Univ Complutense Madrid, Fac Quim, Dept Quim Organ 1, Unidad Asociada,CSIC,Grp Lactamas & Heterociclos, E-28040 Madrid, Spain

[2] CSIC, IQOG, E-28006 Madrid, Spain

[3] Univ Oviedo, Dept Quim Fis & Analit, Oviedo 33006, Asturias, Spain

关键词: Alkynes;    Cyclization;    Gold;    Lactams;    Reaction mechanisms;   

DOI  :  10.1016/j.tet.2012.03.028

来源: Elsevier

【 摘 要 】

2-Azetidinone-tethered alkyn-1,2-diols or alkynyl acetonides, readily prepared from imines of (R)-2,3-O-isopropylideneglyceraldehyde, were used as starting materials for the regio- and diastereospecific catalytic bis-oxycyclization reaction in the presence of a gold/acid binary system. Interestingly, in contrast to the gold-catalyzed reactions of N-tethered terminal alkynes, which lead to the corresponding 6,8-dioxabicyclo[3.2.1]octane derivatives (proximal adduct), the reactions of substituted alkynic diols and acetonides under identical conditions gave the 7,9-dioxabicyclo[4.2.1]nonane derivatives (distal adducts) as the sole products, through exclusive 7-endo/5-exo bis-oxycyclizations by initial attack of the oxygen atom to the external alkyne carbon. Moreover, the mildness of the method allowed the incorporation of a 1,3-diyne moiety as reactive partner, displaying exquisite chemoselectivity toward the internal alkynic moiety. In order to confirm the mechanistic proposal, labeling studies with deuterium oxide have been performed. Besides, density functional calculations were performed to gain insight into the mechanisms of the bis-oxycyclization reactions. (C) 2012 Elsevier Ltd. All rights reserved.

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