Mechanism of the intramolecular cyclization of acetylenic ketones

Abstract

Acid-catalyzed intramolecular cyclization of S-cyclodecynone (1) under a variety of conditione givee bicyclo-[4.4.0]-1(6)-decen-2-0ne (6) as the only product. In a recent report, evidence for a reaction mechanism involving tranaannular triplebond participation with a polarized carbonyl group followed by attack of the original carbonyl oxygen on the developing vinyl cation to give an unstable oxete intermediate (4) was presented. Subsequently, several workers have euggested a mechanism involving acid-catalyzed enolization of 1, followed by the tranaennular attack of the enol double bond at the acetylenic function, as the first two step in an alternate procew for explaining this rearrangement. When 6-octyn-2-one (9) was treated with either mineral or Lewis acids, a mixture of l-acetyl-2-methyl-l-cyclopentene (12) and 2,3-dimethyl-2-cyclohexen-l-one (14) were produced. Experimenta have shown that the oxygen atoms in the etarting acelylenic ketone 9 are the same onee found in the cyclic products 12 and 14. A mechanism involving cyclization of enol intermediatea cannot account for the formation of 14. On the 0 t h hand, formation and rearrangement of oxete intermediatee demonstrata how both 12 and 14 are produced.The results from acid-catdyzd cyclization of 6-oc@n-2-one (9) are also compared to those reported for the eolvolysis of the taylata of 6-0ctyn-2-01 (18). of the NSF-ILI program (Grant No. USE8661276) for funds used in the purchase of the GC/MS system and the UT Martin Faculty Rmearch Office for its support of this work. -try No. 9,2439546-0; 12,3168-90-9; 14,1122-2@9; ethyl propionylacetate, 4949-44-4; vinyl ketone, 78-94-4; ethyl 50x0-2-propionylhexanoate, 55262-18-5; 2,3-epoxy-2,3-dimethylcyclohexanone, 35502-46-6.(19) Schreiber, J.; Felix, D.; Eechenmoeer, A.; Winter, M.; Gautachi, F.; schulte-ate, K. H.; Sundt, E.; Ohloff, G.; Kalvoda, J.; Kaufmann, H.; Weiland, P.; h e n , G. Helu. Chim. Acta 1967,50,2101.

One‐Pot Synthesis of Naphtho[1′,2′:4,5]imidazo[1,2‐a]pyridin‐5‐yl(aryl)methanones through Sequential Sonogashira Coupling/Alkyne–Carbonyl Metathesis

“…Such reactions can enable the generation of huge libraries of scaffolds for high‐throughput screening, which is a key requisite in the drug discovery process. Alkyne‐carbonyl metathesis (ACM) represents a valuable tool for the synthesis of substituted α, β‐unsaturated carbonyl compounds by a [2+2] cycloaddition and cyclo‐reversion process between the C–O double bond and the C–C triple bond in an atom‐economical manner, which is a viable alternative to traditional aldol and Wittig reactions for the construction of C–C double bonds …”

Tandem Brønsted Acid Promoted and Nazarov Carbocyclizations of Enyne Acetals to Hydroazulenones

“…We believe the mechanism of the tandem carbocyclizations of enyne acetals 1 and 4 most likely starts with the Brønsted acid induced formation of the electrophilic oxonium species A (Scheme ) 32. This cationic species would undergo standard heteroalkyne metathesis to the oxete intermediate B (through [2+2] cycloaddition),17a which upon ring opening would give the divinyl ketone C . Subsequently, the Brønsted acid would induce a stereospecific Nazarov reaction (4πe − electrocyclization)18 of this unpolarized25d dienone C to give one of two possible oxyallyl cations, D and E , depending whether the starting compound had been β or α substituted.…”

Interrupted Carbonyl‐Alkyne Metathesis

“…[12] Specifically, a distinct fragmentation of the oxetane via intermediate benzylic carbocations enabled an oxygen-atom-transfer step to ultimately yield the tricyclic products. [13] The reaction similarly relies on an initial [2 + 2]-cycloaddition and a subsequent ring-opening transitioning through a strained oxetene intermediate. [13] The reaction similarly relies on an initial [2 + 2]-cycloaddition and a subsequent ring-opening transitioning through a strained oxetene intermediate.…”

“…Additionally, alkynecarbonyl metathesis relying on Lewis or Brønsted acids has been recognized as an efficient strategy to access substituted enones 5 from carbonyl and alkyne precursors 4 ( Figure 1C). [13] The reaction similarly relies on an initial [2 + 2]-cycloaddition and a subsequent ring-opening transitioning through a strained oxetene intermediate. We herein report that aryl ketones 4 bearing a pendant alkyne can also result in the formation of dihydrofluorenes 6 when converted under catalytic amounts of Lewis acidic superelectrophile [14] ( Figure 1D).…”