83497-94-3Relevant articles and documents
Metalated Nitriles: Halogen - Metal Exchange with α-Halonitriles
Fleming, Fraser F.,Zhang, Zhiyu,Knochel, Paul
, p. 501 - 503 (2004)
(Equation presented) α-Halonitriles react with organometallic reagents in a facile halogen-metal exchange. The halogen-metal exchange is extremely fast with Grignard and alkyllithium reagents, generating metalated nitriles in situ with aldehyde, ketone, a
Utilization of achiral alkenyl amines for the preparation of high affinity Grb2 SH2 domain-binding macrocycles by ring-closing metathesis
Liu, Fa,Worthy, Karen M.,Bindu, Lakshman,Giubellino, Alessio,Bottaro, Donald P.,Fisher, Robert J.,Burke Jr., Terrence R.
, p. 367 - 372 (2008/03/27)
A family of previously reported ring-closing metathesis (RCM)-derived macrocycles that exhibit potent Grb2 SH2 domain-binding affinity is characterized by stereoselectively-introduced upper ring junctions that bear bicyclic aryl substituents. However, the synthetic complexity of these macrocycles presents a potential limit to their therapeutic application. Therefore, the current study was undertaken to simplify these macrocycles through the use of achiral 4-pentenylamides as ring-forming components. A series of macrocycles (5a-f) was prepared bearing both open and cyclic constructs at the upper ring junction. The Grb2 SH2 domain-binding affinities of these macrocycles varied, with higher affinities being obtained with cyclo-substituents. The most potent analogue (5d) contained a cyclohexyl group and exhibited Grb2 SH2 domain-binding affinity (KD = 1.3 nM) that was nearly equal to the parent macrocycle (2), which bore a stereoselectively- introduced naphthylmethyl substituent at the upper ring junction (KD = 0.9 nM). The results of this study advance design considerations that should facilitate the development of Grb2 SH2 domain-binding antagonists. This journal is The Royal Society of Chemistry.
Metalated nitriles: Organolithium, -magnesium? and -copper exchange of α-halonitriles
Fleming, Fraser F.,Zhang, Zhiyu,Liu, Wang,Knochel, Paul
, p. 2200 - 2205 (2007/10/03)
(Chemical Equation Presented) α-Halonitriles react with alkyllithium, organomagnesium, and lithium dimethylcuprate reagents generating reactive, metalated nitriles. The rapid halogen-metal exchange with alkyllithium and Grignard reagents allows selective exchange in the presence of reactive carbonyl electrophiles, including aldehydes, providing a high-yielding alkylation protocol. Lithiated and magnesiated nitriles react with propargyl bromide by SN2 displacement whereas organocopper nitriles react by S N2′ displacement, correlating with the formation of a C-metalated nitrile.
