Enantioselective deprotonation of 4-tert-butylcyclohexanone by conformationally constrained chiral lithium amide bases

Stereoselective synthesis of 1,3-disubstituted dihydroisoquinolines vial-phenylalanine-derived dihydroisoquinoline N-oxides

“…Our approach to nitrone 3 centred on the oxidation of the known amine 5 (Scheme 2), accessed by Pictet-Spengler reaction of L-phenylalanine, 13 followed by borane-mediated reduction of the resulting acid. 5 Trialing a range of methods for the direct oxidative conversion of amines to nitrones, revealed that the corresponding isoquinoline N-oxide was a significant byproduct. Best results were achieved using Oxone as oxidant, providing dihydroisoquinoline derived nitrone 3 cleanly, in moderate yield (58%), with no evidence of overoxidation to the corresponding isoquinoline N-oxide.…”

“…3 Moreover, there is interest in the use of tetrahydroisoquinolines as ligands in asymmetric catalysis 4 and as chiral bases. 5 The methods for accessing 1,3-disubstituted THIQ's, can be broadly grouped into two strategies, based on either cyclisations of suitably substituted aromatic precursors 6 or functionalisation of isoquinoline-based scaffolds. 7 In an effort to develop a strategy towards enantiodefined tetrahydroisoquinolines, of general use, we became interested in an approach of the latter type utilizing a chiral pool-derived isoquinoline unit with a potentially broad reactivity profile.…”

A Synthetic Route to Highly Substituted 1,2,3,4‐Tetrahydroisoquinolines via Yb(OTf)3‐Catalyzed Diastereoselective Ring Opening of Bridged Oxazolidines: Asymmetric Synthesis of 2‐Azapodophyllotoxin

“…Reported approaches for the synthesis of 1,3-anti THIQs involve nucleophilic addition to 3,4-dihydroisoquinoline (DHIQ) precursor as iminium intermediates at very low temperatures; however, these methods achieved a high level of diastereoselectivity via 1,3-asymmetric induction only when a bulky C-3 substituents was pre-installed on the DHIQ precursors. [15] Schreiber and coworkers also utilized DHIQ-derived iminium intermediates to synthesize 1-alkyne-substituted THIQs in the presence of CuBr/QUINAP as catalysts, [16] whereas Inomata et al employed DHIQ-N-oxide for C-1 functionalization using a tartaric-acid-derived chiral auxiliary to obtain 1-substituted THIQs with poor to moderate enantioselectivity. [17] The direct alkylation of a C-1 lithiated THIQ offers an alternative route of synthesis, but this provides only modest diastereoselectivity.…”

Utilizing the intramolecular Fukuyama–Mitsunobu reaction for a flexible synthesis of novel heterocyclic scaffolds for peptidomimetic drug design

“…17 After recrystallization, the amino alcohol 8 was obtained in 78% yield. The optical rotation was in agreement with the value reported in literature.…”