51449-10-6Relevant academic research and scientific papers
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.
supporting information, 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.
From phenylacetylphenylacetic acids and 1-benzylisoquinolines to 6,11-dihydrobenzo[b]naphtho[2,3-d]furan-6,11-diones, 6H-dibenzo[c,h]chroman-6-ones and 7,12-dihydro-5H-dibenzo[c,g]chroman-5,7,12-triones via 2-phenyl-3-hydroxy-1,4-dihydro-1,4-naphthalenediones or 2-phenyl-1-naphthols
Martínez, Elena,Martínez, Luis,Treus, Mónica,Estévez, Juan C.,Estévez, Ramón J.,Castedo, Luis
, p. 6023 - 6030 (2007/10/03)
We describe the synthesis of 6,11-dihydrobenzo[b]naphtho[2,3-d]furane-6,11-diones, 6H-Dibenzo[c,h]chroman-6-ones and 7,12-dihydro-5H-dibenzo[c,g]chroman-5,7,12-triones from 2-(2'-phenyl)-3-hydroxy-1,4-dihydro-1,4-naphthalenediones or 2-phenyl-1-naphthols obtained from 2-(2'-bromophenylacetyl)-phenylacetic acids or 1-benzylisoquinolines. (C) 2000 Elsevier Science Ltd.
New, simple total syntheses of benzo[b]naphtho[2,3-d]furan-6,11-diones and benzo[b]naphtho[2,1-d]furans
Martinez, Elena,Martinez, Luis,Estevez, Juan C.,Estevez, Ramon J.,Castedo, Luis
, p. 2175 - 2176 (2007/10/03)
Here we account the transformation of 2-[(2'- bromophenyl)acetyl]phenylacetic acids and 1-benzylisoquinolines into benzo[b]naphtho[2,3-d]furan-6,11-diones. Synthesis of benzo[b]naphtho[2,1- d]furans from 1-benzylisoquinolines is also described.
Synthetic potential of papaverine derivatives via benzynes
de Lera, Angel Rodriguez,Aubourg, Santiago,Suau, Rafael,Castedo, Luis
, p. 675 - 684 (2007/10/02)
When 6′-bromoderivatives of papaverine and papaveraldine were treated with dimsyl sodium, products which incorporate the reagent are obtained. Under similar conditions 6′-bromopapaverine methiodide afforded the expected aporphine skeleton.
