Gold(I)-promoted heterocyclization of internal alkynes: a comparative study of direct metallate 5-endo-dig
Jonathan M French1, Steven T Diver
1Department of Chemistry, University at Buffalo, the State University of New York , Buffalo, New York 14260, United States.
Abstract:
With cationic gold catalysts, internal alkynes bearing both propargylic acyloxy groups and tosylamide pronucleophiles were found to cyclize to give either five- or six-membered ring nitrogen heterocycles. A wide variety of gold catalysts, counterions, and solvents were examined to elucidate their effect on product distribution. In most cases, the direct 5-endo-dig cyclization was found to be the major pathway leading to good yields of dehydropyrrolidine products. Alkyne substrates bearing additional normal alkyl substituents at the propargylic position gave dehydropiperidines as the major product. This pathway is thought to proceed by way of a 1,2- Rautenstrauch rearrangement to produce a vinyl gold(I) carbene, which undergoes conjugate addition by the nitrogen pronucleophile. Structural and electronic factors were studied in the nitrogen pronucleophile and in the migrating acyloxy group. Each was found to have a minor effect on the product ratio.
More Related Videos
Related Concept Videos
02:47Alkynes to Aldehydes and Ketones: Hydroboration-Oxidation
One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
02:24Reduction of Alkynes to cis-Alkenes: Catalytic Hydrogenation
Like alkenes, alkynes can be reduced to alkanes in the presence of transition metal catalysts such as Pt, Pd, or Ni. The reaction involves two sequential syn additions of hydrogen via a cis-alkene intermediate.
02:40Alkynes to Aldehydes and Ketones: Acid-Catalyzed Hydration
Analogous to alkenes, alkynes also undergo acid-catalyzed hydration. While the addition of water to an alkene gives an alcohol, hydration of alkynes produces different products such as aldehydes and ketones.
02:27Preparation of Alkynes: Alkylation Reaction
Alkylation of terminal alkynes with primary alkyl halides in the presence of a strong base like sodium amide is one of the common methods for the synthesis of longer carbon-chain alkynes. For example, treatment of 1-propyne with sodium amide followed by reaction with ethyl bromide yields 2-pentyne.
02:34Preparation of Alkynes: Dehydrohalogenation
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ammonia. The reaction proceeds with the loss of two equivalents of hydrogen halide (HX) via two successive E2 elimination reactions.
02:38Electrophilic Addition to Alkynes: Halogenation
Halogenation is another class of electrophilic addition reactions where a halogen molecule gets added across a π bond. In alkynes, the presence of two π bonds allows for the addition of two equivalents of halogens (bromine or chlorine). The addition of the first halogen molecule forms a trans-dihaloalkene as the major product and the cis isomer as the minor product. Subsequent addition of the second equivalent yields the tetrahalide.