Enantiodivergent Synthesis of Pyrrolo[2,1-a]isoquinolines Based on Diastereoselective Parham Cyclization and α-Amidoalkylation Reactions

Abstract

Enantiodivergent synthesis of C-10b-substituted pyrrolo[2,1-a]isoquinolines starting from an enantiomerically pure N-phenethylnorborn-5-en-endo-2,3-dicarboxyimide 3a, with a 2-exo-hydroxy-10-bornylsulfinyl group as a chiral auxiliary, has been developed. The key transformations are derived from diastereoselective intramolecular cyclization of aryllithiums and alpha-amidoalkylation reactions, with the ethylidene bridge of the norbornene moiety dictating the stereochemical outcome in both types of reactions. Thus, the organolithium addition-intramolecular alpha-amidoalkylation sequence on imide 3a afforded stereoselectively the R configuration at C-12b, whereas the tandem Parham cyclization-intermolecular alpha-amidoalkylation reactions on the corresponding iodinated imide 3b occurred with complete control of stereoselectivity, leading to the epimer at C-12b. Subsequent reductive removal of the chiral auxiliary and retro-Diels-Alder reaction afforded (10bS)- and (10bR)-pyrroloisoquinolines 1 in high yields and optical purities (>99% ee).

Use of samarium diiodide in the field of asymmetric synthesis

“…Lete et al have reported the asymmetric synthesis of pyrrolo[2,1-a]isoquinolines 54 starting from enantiopure sulfinylmaleimide 49 (Scheme 12). 32 Reaction of 49 with cyclopentadiene followed by alkyl lithium, afforded ahydroxylactams 50 in quantitative yields as single diastereoisomers. Treatment of 50 with an excess of TFA at room temperature furnished isoquinolines 51, together with their derivatives 52, in which trifluoroacetylation of the hydroxyl group of the auxiliary had occurred.…”

Synthesis of Chiral CF3‐Contaning Pinane‐Type Hydroxythiols

“…Terpene thiols can be used as intermediates in organic synthesis to produce sulfochlorides, [15–17] sulfonamides, [18] sulfides, [4,8,9,19] disulfides, [5,20] sulfenimines and sulfinimines [7,21–25] . Chiral monoterpene hydroxythiols can also be used as chiral ligands or organocatalysts in asymmetric catalysis and as chiral auxiliaries in asymmetric synthesis [26–36] . Previously, we have developed methods for producing monoterpene menthane, [20,21] bornane, [22] pinane [37] and carane thiols [38] …”

Synthesis of Novel N-Heterocyclic Compounds Containing 1,2,3-Triazole Ring System via Domino, “Click” and RDA Reactions

“…For synthetic chemists, the RDA reaction has become a valuable tool for their research towards the design and synthesis of novel heterocyclic scaffolds, because of its efficiency in introducing a double bond into a heterocyclic skeleton [40] along with enantiocontrolled [41] and enantiodivergent [42] syntheses of heterocyclic compounds.…”