126798-70-7Relevant articles and documents
Direct 1,4-difunctionalization of isoquinoline
Lou?rat, Frédéric,Fort, Yves,Mamane, Victor
, p. 5716 - 5718 (2009)
The synthesis of 1,4-disubstituted isoquinoline derivatives was achieved in one step starting from isoquinoline. The process involved a nucleophilic addition in 1-position followed by an electrophilic trapping in 4-position. Interesting features were noted when C2Cl6 was used as the electrophile since different compounds could be isolated selectively only by adjusting the reaction parameters.
Site-Selective C–H Functionalization of (Hetero)Arenes via Transient, Non-symmetric Iodanes
Fosu, Stacy C.,Hambira, Chido M.,Chen, Andrew D.,Fuchs, James R.,Nagib, David A.
, p. 417 - 428 (2019/02/14)
Fosu, Hambira, and colleagues describe the direct C–H functionalization of medicinally relevant arenes or heteroarenes. This strategy is enabled by transient generation of reactive, non-symmetric iodanes from anions and PhI(OAc)2. The site-selective incorporation of Cl, Br, OMs, OTs, and OTf to complex molecules, including within medicines and natural products, can be conducted by the operationally simple procedure included herein. A computational model for predicting site selectivity is also included. The discovery of new medicines is a time- and labor-intensive process that frequently requires over a decade to complete. A major bottleneck is the synthesis of drug candidates, wherein each complex molecule must be prepared individually via a multi-step synthesis, frequently requiring a week of effort per molecule for thousands of candidates. As an alternate strategy, direct, post-synthetic functionalization of a lead candidate could enable this diversification in a single operation. In this article, we describe a new method for direct manipulation of drug-like molecules by incorporation of motifs with either known pharmaceutical value (halides) or that permit subsequent conversion (pseudo-halides) to medicinally relevant analogs. This user-friendly strategy is enabled by combining commercial iodine reagents with salts and acids. We expect this simple method for selective, post-synthetic incorporation of molecular diversity will streamline the discovery of new medicines. A strategy for C–H functionalization of arenes and heteroarenes has been developed to allow site-selective incorporation of various anions, including Cl, Br, OMs, OTs, and OTf. This approach is enabled by in situ generation of reactive, non-symmetric iodanes by combining anions and bench-stable PhI(OAc)2. The utility of this mechanism is demonstrated via para-selective chlorination of medicinally relevant arenes, as well as site-selective C–H chlorination of heteroarenes. Spectroscopic, computational, and competition experiments describe the unique nature, reactivity, and selectivity of these transient, unsymmetrical iodanes.
Heterocyclic Enamides Studies. I. Preparation of 4-Bromo- and 4-Chloroisoquinolines from 1,2-Dihydroisoquinoline Derivatives
Urbanski, Jerzy,Wrobel, Leszek
, p. 417 - 424 (2007/10/02)
The reactions of isoquinoline Reissert compounds analogs 1 with bromine and phosphorus pentachloride as well as the hydrolysis of enamides 1, 2 and 3 have been studied.Compounds 1 treated with bromine in most cases undergo bromination of unsaturated carbon C-4; when treated with PCl5 only 1-phenyl and 1-(2,4,6-trinitrobenzyl) derivatives undergo analogous chlorination.Acidic or basic hydrolysis of starting enamides and their 4-halogeno derivatives results in aromatization with splitting off or retention of substituents at C-1.The sequence of reactions studied can be used as a new interesting route to some 4-bromo or 4-chloroisoquinolines.
