Selectivity in Garratt−Braverman Cyclization: An Experimental and Computational Study

Abstract

Bispropargyl sulfones equipped with aromatic rings of dissimilar nature were synthesized. Under basic conditions, these sulfones isomerized to the bisallenic sulfones, creating a competitive scenario between two alternate Garratt-Braverman (GB) cyclization pathways. The observed product distribution ruled out the involvement of any ionic intermediate and supported the diradical mechanism with greater involvement of the electron-rich aromatic ring via the more nucleophilic radical. DFT-based calculations supported the diradical mechanism along with the observed selectivity.

Theoretical Support for the Involvement of a Radical Pathway in the Formation of Allenylzincs from Propargyl Iodides and Dialkylzincs: Influence of Zinc Coordination

“…The residue was purified through flash column chromatography to give product 8y (5.5 g, 80% yield) as colorless liquid. 1 7-Methoxyhept-2-yn-1-ol (8z): 39 To a solution of 2-(7-methoxyhept-2-ynyloxy)-tetrahydro-2H-pyran (8y) (2.42 g, 10.7 mmol) in 100 mL of ethanol was added pyridinium p-toluenesulfonate (2.68 g, 10.7 mmol) slowly at room temperature over 30 min. After addition completion, the reaction mixture was heated at 50°C for 12 h. Ethanol was evaporated and the resulted residue was purified through flash column chromatography to get product 8z as colorless liquid in 80% yield (1.…”

Base‐Induced Cyclization of Propargyl ­Alkenylsulfones: A High‐Yielding Synthesis of 4,5‐Disubstituted 2H‐Thiopyran 1,1‐Dioxides

“…The key step was a K 2 CO 3 -mediated S-alkylation [10] of an alkenyl thiol, generated in situ from the corresponding thioacetate [11] 8A-8C, with a propargyl bromide 9A-9M (all the bromides are reported in the literature [4,12] ). The key step was a K 2 CO 3 -mediated S-alkylation [10] of an alkenyl thiol, generated in situ from the corresponding thioacetate [11] 8A-8C, with a propargyl bromide 9A-9M (all the bromides are reported in the literature [4,12] ).…”

“…[1] The reaction leads to the formation of two C-C bonds in high yield under mild conditions, and is popularly known as the Garratt-Braverman (GB) cyclization. [3] Although doubts remain about the exact mechanism of the reaction, a diradical mechanism involving a bis-allene intermediate (Scheme 1), as proposed initially by Garratt and Braverman and later supported by computations and selectivity profiles, [4] is the generally accepted one. [3] Although doubts remain about the exact mechanism of the reaction, a diradical mechanism involving a bis-allene intermediate (Scheme 1), as proposed initially by Garratt and Braverman and later supported by computations and selectivity profiles, [4] is the generally accepted one.…”

Enediynes, enyne‐allenes, their reactions, and beyond

“…Interesting in this connection is the Garatt–Braverman cyclization, which involves a double allene reaction with subsequent biradical formation . As an example, the rearrangement of a bispropagyl sulfone is shown in Figure , which isomerizes in alkaline media to an allenic sulfone and then transforms into a bioactive biradial at ambient temperatures …”