Gold-Catalyzed Stereoselective Synthesis of 9-Oxabicyclo[3.3.1]nona-4,7-dienes from Diverse 1-Oxo-4-oxy-5-ynes: A Viable Formal [4 + 2] Cycloaddition on ans-trans-Heterodiene Framework

Abstract

We report a highly stereoselective Au-catalyzed synthesis of 9-oxabicyclo[3.3.1]nona-4,7-dienes from diverse 1-oxo-4-oxy-5-ynes. Formation of these highly strained anti-Bredt oxacycles implies the workability of an unprecedented 1,4-dipole of s-trans-methylene(vinyl)oxonium. This work reveals the feasibility of a formal [4 + 2] cycloaddition on an s-trans-heterodiene framework.

Recent developments in gold-catalyzed cycloaddition reactions

“…In contrast to these examples that proceed through an initial endo-dig cyclization and generate gold–carbonyl ylide species, the group of Liu recently demonstrated that it is also possible to produce alternative, reactive, zwitterionic intermediates of type IV through an exo-dig cyclization process when using 1-oxo-5-ynes such as 3 and a cationic gold complex prepared in situ from P( t -Bu) 2 ( o -biphenyl)AuCl ( Au1 ) [39] and AgNTf 2 [40]. These dipolar intermediates undergo a cycloaddition with an external vinyl ether 4 , leading to interesting 9-oxabicyclo[3.3.1]nona-4,7-dienes 5 in good yields (Scheme 2).…”

“…A final elimination process regenerates the catalyst and affords the oxacyclic product 5 . Importantly, the reaction also proceeds with non-aromatic 1-oxo-4-alkoxy-5-ynes [40]. …”

Gold-catalyzed cyclization of allenyl acetal derivatives

“…Such cascade reactions have been well studied on various difunctionalized molecules including oxoalkynes [6–13], oxoallenes [14], oxoalkenes [15] and allenyl acetals [16–18]. In this cascade sequence, two new rings and three chemical bonds are generated in a one-pot procedure.…”

Silver‐Catalyzed exo‐dig‐Azacyclization/[3+2] Cycloaddition Cascades on 1‐Tosylhydrazon‐4‐oxy‐5‐yne Substrates: Applicability to Diverse Alkenes

“…(2)]. [5] With this catalyst mixture, we obtained azacyclic product 3a in 66% yield (entry 1). Our control experiment reveals that AgNTf 2 (5 mol%) alone implemented this cascade reaction to produce the same product in 58% yield (entry 2).…”

“…Acetoxy (OAc) and methoxymethyl (MOM) ethers presumably exert an electron-withdrawing effect on the adja-cent alkyne to enhance the 6-exo-dig cyclization mode. [5] We prepared various 1-tosylhydrazon-4-acetoxy-5yne derivatives 4a-4e and 5a-5d to examine the generality of this exo-azacyclization/A C H T U N G T R E N N U N G [3+2] cycloaddition cascade. In a standard operation, these substrates were treated with ethoxyethene (4 equiv.)…”