Accessing simply-substituted 4-hydroxytetrahydroisoquinolines via Pomeranz–Fritsch–Bobbitt reaction with non-activated and moderately-activated systems

• Marco Mottinelli,
• Mathew P. Leese and
• Barry V. L. Potter

Beilstein J. Org. Chem. 2017, 13, 1871–1878, doi:10.3762/bjoc.13.182

• ; steroidomimetic; synthesis; tetrahydroisoquinoline; Introduction 1,2,3,4-Tetrahydroisoquinoline (THIQ) motifs are present in many natural alkaloids [1]. THIQ derivatives have also been investigated as potential therapeutics in a wide range of diseases and recent studies have explored their potential as

• deliver the 1,2,3,4-tetrahydroisoquinoline product. Relative to the original Pomeranz–Fritsch conditions, the Bobbitt modification features a reduced acid concentration that advantageously reduces the formation of side products [8][9][10]. The key cyclization in the PFB synthesis reaction is an

• to access libraries of regioisomeric N-aryl-1,2,3,4-tetrahydroisoquinoline derivatives that might facilitate the design of new structural templates for steroid-binding receptors. We thus evaluated the robustness and flexibility of this approach to the THIQ system and considered, in particular, the

Brønsted acid-mediated cyclization–dehydrosulfonylation/reduction sequences: An easy access to pyrazinoisoquinolines and pyridopyrazines

• Ramana Sreenivasa Rao and
• Chinnasamy Ramaraj Ramanathan

Beilstein J. Org. Chem. 2017, 13, 428–440, doi:10.3762/bjoc.13.46

• , recently, we have reported the activation of an imide carbonyl group with TfOH, for the synthesis of tetrahydroisoquinoline (THIQ) and tetrahydro-β-carboline (THBC) skeletons and related alkaloids [22][23][24][25][26]. The present study, describes the synthesis of 4-benzenesulfonylpiperazine-2,6-dione

• exemplified by the successful synthesis of fused tetrahydroisoquinoline drug molecule, praziquantel. Extending this strategy towards the stereoselective reduction of pyrazinones/ene-diamides is under investigation in our laboratory. Experimental General procedure for the synthesis of 4

Copper-catalyzed asymmetric sp³ C–H arylation of tetrahydroisoquinoline mediated by a visible light photoredox catalyst

• Pierre Querard,
• Inna Perepichka,
• Eli Zysman-Colman and
• Chao-Jun Li

Beilstein J. Org. Chem. 2016, 12, 2636–2643, doi:10.3762/bjoc.12.260

• reaction yielded 3a with good enantiomeric ratio (Table 3, entry 1). In the presence of the other enantiomer of L2, (S,S)-PhPyBox, the reaction afforded good er. When N-(2-methhoxyphenyl)tetrahydroisoquinoline was used, the corresponding enantiomer was obtained with similar enantioselectivity (Table 3

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• tetrahydroisoquinoline [53][54] gave the carbonylation product directly. However, when piperazine substrates were used, an additional formal dehydrogenation process took place before the carbonylation reaction. As shown in Figure 13, under the conditions of 15 atm of carbon monoxide and ethylene, Rh4(CO)12 catalyst, and

Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

• Jixin Liu,
• Srimoyee Dasgupta and
• Mary P. Watson

Beilstein J. Org. Chem. 2015, 11, 2696–2706, doi:10.3762/bjoc.11.290

• alkynes to deliver racemic products [23], the Li group developed a CuOTf/Ph-Pybox catalyst system that enables alkynylation of tetrahydroisoquinolines in moderate to good yields and enantioselectivies (Scheme 3). A particularly powerful aspect of this chemistry is that a stable tetrahydroisoquinoline 6

• can be utilized as the substrate. Oxidation of the tetrahydroisoquinoline then results in formation of iminium ion 7 in situ. As in Knochel’s reaction above, the highest yields and ee’s were observed with arylacetylenes. In subsequent studies of this reaction, Li investigated the intermediacy of

3-Glucosylated 5-amino-1,2,4-oxadiazoles: synthesis and evaluation as glycogen phosphorylase inhibitors

• Marion Donnier-Maréchal,
• David Goyard,
• Vincent Folliard,
• Tibor Docsa,
• Pal Gergely,
• Jean-Pierre Praly and
• Sébastien Vidal

Beilstein J. Org. Chem. 2015, 11, 499–503, doi:10.3762/bjoc.11.56

• selected (Scheme 1, b and c) for their expected hydrophobic contact with the enzyme. The tetrahydroisoquinoline moiety (Scheme 1, c) was particularly interesting due to its structural analogy with the 2-naphthyl residue, which is identified as the best pharmacophore in the GP inhibitor series. The

One-pot functionalisation of N-substituted tetrahydroisoquinolines by photooxidation and tunable organometallic trapping of iminium intermediates

• Joshua P. Barham,
• Matthew P. John and
• John A. Murphy

Beilstein J. Org. Chem. 2014, 10, 2981–2988, doi:10.3762/bjoc.10.316

• . Keywords: iminium salt; organometallic; oxidative functionalisation; photoredox catalysis; tetrahydroisoquinoline; Introduction Tetrahydroisoquinolines (THIQs) are structural motifs prominent within biologically active natural products and pharmaceutical compounds [1][2]. From (−)-carnegine (1, a

Lewis acid-catalyzed redox-neutral amination of 2-(3-pyrroline-1-yl)benzaldehydes via intramolecular [1,5]-hydride shift/isomerization reaction

• Chun-Huan Jiang,
• Xiantao Lei,
• Le Zhen,
• Hong-Jin Du,
• Xiaoan Wen,
• Qing-Long Xu and
• Hongbin Sun

Beilstein J. Org. Chem. 2014, 10, 2892–2896, doi:10.3762/bjoc.10.306

• amines were also good substrates for this reaction, affording the desired products (3q, 3r, 3s) in good to high yields (77–98% yields) with DCE as the solvent under reflux conditions. The reaction with indoline, tetrahydroquinoline, and tetrahydroisoquinoline could also be realized to give products 3t

Exploration of C–H and N–H-bond functionalization towards 1-(1,2-diarylindol-3-yl)tetrahydroisoquinolines

• Michael Ghobrial,
• Marko D. Mihovilovic and
• Michael Schnürch

Beilstein J. Org. Chem. 2014, 10, 2186–2199, doi:10.3762/bjoc.10.226

• towards 1-(1,2-diarylindol-3-yl)-N-PG-THIQs (PG = protecting group, THIQ = tetrahydroisoquinoline) employing transition metal-catalyzed C–H and N–H-bond functionalization were explored. It was found that the synthesis of the target compounds is strongly dependent on the order of events. Hence, depending

Chromatographically separable rotamers of an unhindered amide

• Mario Geffe,
• Lars Andernach,
• Oliver Trapp and
• Till Opatz

Beilstein J. Org. Chem. 2014, 10, 701–706, doi:10.3762/bjoc.10.63

• .10.63 Abstract Surprisingly stable formamide rotamers were encountered in the tetrahydroisoquinoline and morphinan series of alkaloids. We investigated the hindered rotation around the amide bond by dynamic high-performance liquid chromatography (DHPLC) and kinetic measurements of the interconversion of

• for the syntheses of various isoquinoline alkaloids [5][6][7]. Spontaneous dehydrocyanation afforded the 1-benzylated 3,4-dihydroisoquinoline which was subsequently reduced in situ to tetrahydroisoquinoline 3 in a one-pot procedure with sodium borohydride in 63% yield. N-Acylation was effected

• larger size of the molecule and its considerable conformational freedom may contribute to this deviation. Calculations on the model compound 1-benzyl-N-formyl-1,2,3,4-tetrahydroisoquinoline at the same level of theory showed that either the E- or the Z-ground state can be lower in energy depending on the

Studies toward bivalent κ opioids derived from salvinorin A: heteromethylation of the furan ring reduces affinity

• Thomas A. Munro,
• Wei Xu,
• Douglas M. Ho,
• Lee-Yuan Liu-Chen and
• Bruce M. Cohen

Beilstein J. Org. Chem. 2013, 9, 2916–2924, doi:10.3762/bjoc.9.328

• well. The tetrahydroisoquinoline moiety of JDTic adopts a pose almost identical to that of naltrindole; the superimposable atoms are shown in pink in Figure 2B [10]. JDTic is thus a bivalent ligand, containing two linked pharmacophores [12], also known as a linked multiple ligand [13]. Bivalent ligands

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• of the (R)-quinuclidinol and tetrahydroisoquinoline carbamate partner (Scheme 28). The (R)-quinuclidinol (2.59) itself can be accessed from quinuclidone (2.60), and is most conveniently prepared by alkylation of ethyl isonicotinate (2.61) with ethyl bromoacetate (2.62) followed by full reduction of

• racemic quinuclidinol. However, an improved approach makes use of a Noyori-type asymmetric reduction employing a BINAP ligated RuCl2 and a chiral diamine to yield the desired (R)-quinuclidine in high yield and enantioselectivity [78]. The enantioselective synthesis of the tetrahydroisoquinoline fragment

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• cycloaddition is shown in Scheme 13. The reaction commences with oxidation of tetrahydroisoquinoline 41 to amine radical cation 48 by the photoexcited state of Ru2+. Subsequently, abstraction of a hydrogen atom α to the nitrogen atom of 48 yields iminium ion 49, which is then converted to azomethine ylide 50 by

Selective copper(II) acetate and potassium iodide catalyzed oxidation of aminals to dihydroquinazoline and quinazolinone alkaloids

• Matthew T. Richers,
• Chenfei Zhao and
• Daniel Seidel

Beilstein J. Org. Chem. 2013, 9, 1194–1201, doi:10.3762/bjoc.9.135

• yields from tetrahydroisoquinoline-aminal 15, rutaecarpane-derived product 18 was formed in only 47% yield, apparently due to unidentified side-reactions. The reaction leading to the synthesis of the dibromo- analogue of deoxyvasicine 20, even under elevated temperature and extended reaction time, still

Multicomponent reaction access to complex quinolines via oxidation of the Povarov adducts

• Esther Vicente-García,
• Rosario Ramón,
• Sara Preciado and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2011, 7, 980–987, doi:10.3762/bjoc.7.110

• , chemical manganese dioxide (CMD) has been widely used in this type of transformations, and already in 1982 the oxidation of tetrahydroisoquinoline (11, Scheme 2) was reported to yield the corresponding isoquinoline 12, the intermediate dihydroisoquinoline 13 being obtained as a by-product [26]. Later

A short synthesis of (±)-cherylline dimethyl ether

• Bhima Y. Kale,
• Ananta D. Shinde,
• Swapnil S. Sonar,
• Bapurao B. Shingate,
• Sanjeev Kumar,
• Samir Ghosh,
• Soodamani Venugopal and
• Murlidhar S. Shingare

Beilstein J. Org. Chem. 2009, 5, No. 80, doi:10.3762/bjoc.5.80

• short and efficient method for the synthesis of (±)-cherylline dimethyl ether. The simple and facile nature of this tetrahydroisoquinoline synthesis should allow the construction of a wide variety of interesting and useful analogous molecules. Experimental Materials and Instruments All solvents and