Synthesis of 5-Hydrazino-2-cyclopentenone Derivatives by a Gold(I)-Catalyzed Cycloisomerization/Hetero-Diels–Alder/Ring-Opening Tandem Reaction of Enynyl Acetates

Abstract

A highly efficient, one-pot synthesis of ring-fused 5-hydrazino-2-cyclopentenone derivatives is achieved by a gold(I)-catalyzed cycloisomerization/hetero-Diels–Alder/ring-opening tandem reaction of suitable enynyl acetates. By mixing the latter with a dialkylazodicarboxylate in the presence of a gold(I) catalyst, the 1,3-acyloxy migration/Nazarov cyclization process leads to dienyl acetate intermediates which are trapped by the heterodienophile present in situ. This provides strained intermediates which undergo highly regioselective ring opening by a retro aza-Michael reaction promoted by traces of water, eventually yielding the target compounds. Six- and seven-membered ring-fused cyclopentenones and piperidine- and tetrahydropyran-fused cyclopentenones bearing a pendant hydrazino functionality on a bridgehead carbon atom can be obtained in high yield (68–96%) by this approach.

A Tandem Aldol Condensation/Diels‐Alder Sequence of Reactions for One‐Pot Synthesis of a New Series of Polysubstituted‐Decalines

“…, [13] leading to efficient synthesis of pharmaceuticals, [14] natural products, [15] and other molecules of choice. [16] Illustrative multicomponent syntheses involving a DA reaction as the key step include a tandem sequential double DA/ Nazarov reaction in an unsymmetrically substituted diynone to yield a tricyclic scaffolds (such as taiwaniaquinol D), [17] the synthesis of chromenoquinolones via an imine formation/aza-DA/aromatization tandem process, [18] a sequence of DA and intramolecular [3 + 2] cycloadditions of dienylcyclopropane 1,1diesters for rapid construction of fused carbocyclic structures (such as brussonol), [19] a domino Knoevenagel-hetero-DA reaction to access various chromenones, [20] a twelve-step synthetic rout, having the DA reaction as the key step, to the structural core of aflavinines, [21] synthesis of ring-fused 2-cyclopentenone moieties, found in the skeleton of many natural and bioactive compounds like helenalin, via a gold-catalyzed cycloisomerization/hetero-DA/ring-opening sequence of tandem reactions of enynyl acetates, [22] an organocatalyzed sequence of oxa-Michael/Michael/Michael/aldol condensation reactions followed by an intramolecular DA cycloaddition leading to asymmetric synthesis of functionalized tricycles, [23] asymmetric multicomponent synthesis of bioactive alkaloid-type polycycles through catalytic aza-DA reaction of indoles having oxetane as the directing group, [24] and a tandem aldol condensation-DAaromatization sequence of reactions to access 2-tetralones (like serteraline) [25] [Figure 1].…”

Gold-Catalyzed Double Spirocyclization of 3-Ene-1,7-diyne Esters to Dispiroheterocycles

“…Subsequent Nazarov cyclization and concomitant spirocyclization might ensue produce the spiro [4,n]alkenyl-substituted gold carbene species III. 2 For reactions of substrates containing a 6-or 12-and 15-membered ring, it is thought that the electrophilic character of the corresponding gold-bound adduct makes it predisposed to a second spirocyclization. Involving attack of the remaining pendant alkynyl motif to the C�C bond of the five-membered ring system in the intermediate, this lead to 5-exo-trig cyclization and formation of the resonance-stabilized alkylidene cation species IV.…”