Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• [2.3.1]-bicyclic alkenes 158 for the synthesis of isoquinoline (160) or isoquinolone-fused bicycles 162 (Scheme 28) [74]. Compared to their previous C–H functionalization reaction (Scheme 27) [73], no ring opening was observed. This reaction with O-acetyl ketoximes was amenable to a variety of para

Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• from good to excellent. While the scope of the 3(2H)-isoquinolone synthesis was substantially expanded by these findings compared to the previously reported results [21], certain limitations were also noted. For example, attempts to involve imines derived from ethyl glyoxylate, cyclohexanone, and

• , less electron-rich arenes furnished higher amounts of the 3-isoquinolone 15 byproduct compared to their electron-rich counterparts (cf. 9o vs 9p). Likewise, electron-donating substituents in the 4-diazo-3(2H)-isoquinolone benzene ring increased the tendency of 3-isoquinolones 15 to form (cf. 9(15)f–h

• -isoquinolone byproducts (formed exclusively in the absence of the arene). The extent of this side reaction was found to be dependent on the electronic character of the 1,4-DHIQs and the carbocation-intercepting arene molecule. Considering the pronounced three-dimensional character of 1,2,4-trisubstituted 1,4

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• rhodium(III)-catalyzed intermolecular annulation has been established for the preparation of tetrazole-isoquinolone/pyridone hybrids. Several N-acylaminomethyltetrazoles were reacted with arylacetylenes to form the hybrid products in moderate to very good yields. The method relies on the capacity of the

• . Keywords: C–H activation; cyclization; isoquinolone; multicomponent reaction; tetrazole; Introduction Pyridones and isoquinolones are relevant heterocyclic scaffolds present in numerous bioactive compounds and natural products [1][2][3][4]. Similarly, molecules containing a tetrazole ring exhibit a wide

• could form isoquinolones and pyridones linked to a tetrazole ring, since such class of hybrid compounds is not described in the literature. Several protocols based on C–H activation or metal-catalyzed cyclizations are known to generate the isoquinolone and pyridone moieties and further assist their post

Rhodium-catalyzed C–H functionalization of heteroarenes using indoleBX hypervalent iodine reagents

• Erwann Grenet,
• Ashis Das,
• Paola Caramenti and
• Jérôme Waser

Beilstein J. Org. Chem. 2018, 14, 1208–1214, doi:10.3762/bjoc.14.102

• previously reported [13], 5-substituted pyridinone 5m could not be functionalized. Isoquinolone 7n was prepared in 82% yield. The methodology could also be applied to 4-pyridone in a moderate 57% yield for product 7o. Unfortunately, pyrazin-2-one 5p could not be functionalized. Modification of the

• temperature of 100 °C, leading to the formation of the corresponding isoquinolone in only 38% yield [24]. By employing the milder conditions developed for pyridinones, we were pleased to see that the N-oxide group could be preserved and product 12a was obtained in 60% yield. A methyl substitution in C-2

• cyanoborohydride to deliver the N–H unprotected pyridinone 13 in 74% yield (Scheme 4) [29]. A rearrangement of the N-oxide furnished the corresponding isoquinolone 14 in 62% yield. Conclusion In summary, we have developed the C-6 selective C–H heteroarylation of pyridin-2-ones using indoleBXs as coupling partners

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• hexahydropyrrolo[1,2-b]isoquinolone derivatives fused with benzene 10 that have pronounced three-dimensional features and potentially contain several quaternary carbon centers (Figure 2). The first aspect has been recently recognized [29] as a central principle in drug design ensuring effective interaction of

• to involve 9 in reactions with HPA. Notably, due to its non-planar tetracyclic character, the hexahydropyrrolo[1,2-b]isoquinolone fused with benzene scaffold (present in 10) clearly appears related to (though topologically distinct from) the natural and synthetic camptothecin-like topoisomerase

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• and 1,5-benzodiazepine 95, respectively (Scheme 21). 2.2.7 Isoquinolone-1-phosphonates: From Lewis acid catalyzed 6-endo-dig cyclizations of acetylenic Kabachnik–Fields adducts: A modified Kabachnik–Fields reaction for the synthesis of isoquinoline-1-phosphonate derivatives is the three-component

• corresponding 1,2-dihydropyridin-2-ylphosphonates 111 in the presence of CF3SO3Ag, while in the presence of AuBr3, PdCl2 or I+, they undergo a 5-exo-dig cyclization to give dialkyl 1H-pyrrol-2-ylphosphonates 110 or 112 (Scheme 24). Other cyclization reactions of Kabachnik–Fields adducts into isoquinolone-1

Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

• Charles Dylan Turner and
• Marco A. Ciufolini

Beilstein J. Org. Chem. 2011, 7, 1475–1485, doi:10.3762/bjoc.7.171

• intercepted by diethoxyacetonitrile [36] to furnish isoquinolone 11 directly. Relative to 4, compound 11 lacks an iodo substituent, which was introduced by reaction of the free aldehyde 12 with I2 and Cu(OAc)2 in refluxing AcOH [37]. Only the unprotected 12 performed satisfactorily in this step, which

• retrosynthetic analysis of fredericamycin A. Assembly of the isoquinolone segment of fredericamycin. Synthesis of a naphthalide precursor to the quinoid moiety of fredericamycin. Palladium-mediated cyclization of a fredericamycin model system. Synthesis of the precursor of fredericamycin and the facile air