Exploring Intra- and Intermolecular Alkyne Annulations from Biologically Active Terpenoids to Polycyclic Aromatic Hydrocarbons

Abstract

Various trialkylsilyl-substituted alkynes were utilized to prepare highly functionalized and reactive conjugated 2,4-diynones via Friedel−Crafts acylation reaction. We then developed a highly regioselective Lewis acid promoted (Me₂AlCl) Diels–Alder reaction of these conjugated 2,4-diynones to produce substituted 2-alkynyl-1,4-cyclohexadiene (‘skipped’ cyclohexadiene) products. The scope of this synthetic methodology was studied utilizing a variety of cyclic and acyclic dienes as well as with a diverse array of 2,4-diynones. The synthetic utility of these 2-alkynyl-1,4cyclohexadienes was demonstrated making use of functionalities (alkene and enone moiety) present in these molecules.

A highly regioselective synthesis of 2,3-disubstituted chromen-4-one derivatives was accomplished from readily available internal alkyne and 2-methoxybenzoyl chlorides. This Lewis acid promoted method features relatively mild reaction conditions to synthesize a variety of 2,3-disubstituted chromen-4-one derivatives in one pot with up to 93% yield. The reaction proceeds via a domino intermolecular Friedel-Crafts acylation/intermolecular vinyl carbocation trapping (or oxa-Michael addition)/demethylation reaction sequence. We are able to establish a broad scope of this method and showed a brief synthetic utility of these disubstituted 2,3-didubstiuted chromen-4-one derivatives.

The synthesis of pyreno[a]pyrene based helicene derivatives has been achieved via a four-fold benzannulation reaction of alkynes with 30–49% yield. We have demonstrated an easy and efficient protocol featuring a Suzuki cross-coupling reaction between bis(trifluoromethanesulfonyloxy)naphthalene and various 2,6-diynylphenyl borates followed by triflic acid (TfOH) promoted alkyne benzannulation. The two enantiomers of each of these pyreno[a]pyrene based helicene derivatives were separated using chiral HPLC to study their photophysical and chiroptical properties. Migration of one phenyl substituent was also observed under the reaction conditions (TFA, CH₂Cl₂, rt), producing rearranged side product.

The very first chiral teropyrene derivatives have been synthesized utilizing an InCl3-promoted four-fold benzannulation reaction of alkynes. The X-ray crystallographic analysis of chiral teropyrene showed that the substituents in the bay-regions exhibit considerable repulsion and results in considerable twisting of the polycyclic aromatic hydrocarbon (PAH) backbone to arrive at an end-to-end twist angle 52°. The inversion barrier of the enantiomers was found to be 30 kcal/mol, high enough to allow separation of the enantiomers to study them spectroscopically.