Intramolecular Arylative Ring Opening of Donor‐Acceptor Cyclopropanes in the Presence of Triflic Acid: Synthesis of 9H‐Fluorenes and 9,10‐Dihydrophenanthrenes

Abstract

A unique intramolecular arylative ring opening of 2-biaryl substituted donor-acceptor cyclopropanes in the presence of triflic acid was found, furnishing 9H-fluorenes and 9,10-dihydrophenanthrenes. Chemoselectivity between both products is achieved by modification of the solvent, temperature, and amount of triflic acid. Representative large-scale experiments were also carried out successfully with good outcomes.Donor-acceptor cyclopropanes (DACs) are versatile building blocks in organic synthesis for assembling various classes of compounds. The typical cycloaddition of DACs with unsaturated compounds can be used to construct five-, six-, and sevenmembered carbocyclic and heterocyclic compounds. [1] The nucleophilic ring opening of DACs with a variety of heteroatomatic and carbon nucleophiles is demonstrated as a flexible tool to create CÀ X bonds. [1b-c,f-h,j,2] DACs, particularly 2-aryl cyclopropane-1,1-dicarboxylates, have high ring strain, and the corresponding cation and anion intermediates formed by heterolysis of the cyclopropane ring are relatively stable. As a result, DACs usually serve as 1,3-zwitterionic intermediates under the catalysis of Lewis acid or Brønsted acid, and proceed by nucleophilic addition at their C1 position (Scheme 1a). Recently, generation of 1,2-zwitterions from DACs under specified conditions was explored, [3] and some C2-addition reactions were reported (Scheme 1a). [4] Arylative ring opening of 2-aryl substituted DACs forms substituted diarylmethanes by C1-addition (Scheme 1b). Several arylative nucleophiles have been explored, including indoles, [5] benzo[b]furan, [6] electron-rich arenes, [7] polycyclic aromatic species, [7b,g,8] and arylboronic acids bearing electron-donating groups. [9] All of the arylative reactants are relatively reactive nucleophiles, and most of the arylation reactions are intermolecular. [10] However, it is well known that intramolecular reaction can be relatively easily achieved. Hence we assumed that the intramolecular arylative ring opening of DACs with less reactive arenes was possible. The intramolecular reactions would enlarge the limited range of nucleophiles in this type of reaction.With this perspective, we decided to test the intramolecular arylative ring opening of 2-(2'-biphenyl) cyclopropane-1,1dicarboxylate (1 a) to assess the nucleophilicity of the general aryl group (Table 1). When 1 a was treated with one equivalent of triflic acid (TfOH) at room temperature, the C1-addition product, 9H-fluorene 2 a, was indeed formed, but surprisingly, the C2-addition product, 9,10-dihydrophenanthrene 3 a, was obtained as the major product (entry 1). The proportion of 2 a increased with the increasing temperature (entry 2) or loading amount of TfOH (entry 3-5). An excellent yield (95%) of pure 2 a could be obtained when excess TfOH was used (entry 5). On the contrary, lowering the temperature or loading amount of [a]

Synthesis and Structure Confirmation of Selagibenzophenone C

“…A similar shielding effect in related compounds was previously described by us for compounds 2 and 3 . The observed values are in good agreement with the data reported in the literature for the related compounds [24,25] . The products 11 – 14 were inseparable using column chromatography and therefore, we decided to force the conversion to completion.…”

HFIP in Organic Synthesis

“…Separate computational investigations indicated that HFIP and TfOH cooperatively lowered the activation energy in the ring-opening step by 9.0 kcal/mol . A similar intramolecular arylative ring opening of 2-biaryl-substituted DACs was promoted by a catalytic amount of TfOH in HFIP at 70 °C to provide 9 H -fluorenes . Either TfOH or B­(C 6 F 5 ) 3 in HFIP enabled the ring-opening of DACs with TMSCN …”

Regioselectivity of the SEAr-based cyclizations and SEAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

“…Subsequently in 2017, Li and co-workers also applied the intramolecular Friedel-Crafts acylation strategy to get cyclopenta[e]indol-6-one 29k and cyclohepta[e]indol-6-one 29l from compounds 28k and 28l, respectively (Scheme 10C) [21]. While involved in the synthesis of 9H-fluorenes and 9,10-dihydrophenanthrenes through intramolecular arylative ring-opening of indole-tethered donor-acceptor cyclopropanes, Li and co-workers treated compound 36 with triflic acid (TfOH) in refluxing HFIP (Scheme 13) [24]. The reaction afforded compound 37 in 82% through the regioselective intramolecular ring-opening of the cyclopropane ring at the benzylic carbon atom.…”

“…While involved in the synthesis of 9 H -fluorenes and 9,10-dihydrophenanthrenes through intramolecular arylative ring-opening of indole-tethered donor–acceptor cyclopropanes, Li and co-workers treated compound 36 with triflic acid (TfOH) in refluxing HFIP ( Scheme 13 ) [ 24 ]. The reaction afforded compound 37 in 82% through the regioselective intramolecular ring-opening of the cyclopropane ring at the benzylic carbon atom.…”