Parham Cyclization Research Articles

Stereodivergent Synthesis of Hetero-Fused Isoquinolines by Acyliminium and Metallation Methods

Diastereodivergent syntheses of 1,10b-cis- and 1,10b-trans-thiazolo[4,3-a]isoquinoline systems are reported. The key transformations are based on the intramolecular cyclization of aryllithiums and N-acyliminium ions. With 5-substituted N-phenethylthiazolidinediones as substrates, hydride reduction or the organolithium addition−N-acyliminium cyclization sequence stereoselectively afforded the 1,10b-cis derivatives. Alternatively, the tandem Parham cyclization−hydroxyl reduction using the corresponding iodinated thiazolidinediones occurred with complete control of stereoselectivity, producing the 1,10b-trans diastereomers. Although it was not possible to synthesise imidazo[4,3-a]isoquinolinones by N-acyliminium cyclizations, application of the Parham cyclization−reduction sequence to N-phenethylhydantoins constituted an efficient alternative for the synthesis of these hetero-fused isoquinolines with 1,10b-trans stereochemistry. Ready access to 1-phenethylisoquinolines is also described.

A practical approach to highly functionalized benzodihydrofurans

A number of aromatic dibromides have been treated with 2–3 equivalents of n-butyllithium in order to initiate two sequential chemical events, a Parham cyclization and an intermolecular reaction with DMF.

Synthesis of (1S,5S)‐4,5‐Dihydro‐1,5‐epoxy‐1H‐2‐benzoxocin‐6(3H)‐one from (S)‐Malic Acid Derivatives

AbstractThe homochiral 1,3‐dioxanes 8a–e with a 2‐bromophenyl substituent in position 2 and an electrophilic group in position 4 were stereo‐ and regioselectively prepared from the (S)‐malic acid derivatives 6a, 6b, 11, and 14. Attempts to prepare the tricycles 5a–c by connecting the 2‐phenyl substituent with the electrophilic groups in position 4 of 8a–e in a Parham cyclization across the 1,3‐dioxane ring failed. The synthesis of the tricyclic title ketone 5a succeeded, however, by addition of the lithiated benzaldehyde acetal 7c to the protected α‐hydroxylactone 10b and subsequent treatment of the intermediate ketone 23 with acid. The acid hydrolysis of the alcohol 26, which was obtained by addition of 7c to the protected dihydroxy aldehyde 25b, followed by oxidation of the resulting alcohols 27a and b represent a second possibility for the preparation of the tricyclic ketone 5a.

ChemInform Abstract: Overriding Normal Friedel‐Crafts Regiochemistry in Cycliacylation. Regiospecific Carbodesilylation and Parham Cyclization Routes to 7‐Methoxy‐1‐indanols.

AbstractThe regiospecific synthesis of the indanols (VIII) and indanones (X) is described as outlined in the reaction scheme.

Overriding normal Friedel-Crafts regiochemistry in cycliacylation. Regiospecific carbodesilylation and Parham cyclization routes to 7-methoxy-1-indanols

Regiospecific syntheses of 7-methoxy-1-indanols (11a-c) and -indanones (13a-c) via fluoride-induced carbodesilylation and Parham cyclization processes respectively are reported.