32890-87-2Relevant articles and documents
Method for estimating SN1 rate constants: Solvolytic reactivity of benzoates
Matic, Mirela,Denegri, Bernard,Kronja, Olga
supporting information, p. 8986 - 8998,13 (2012/12/12)
Nucleofugalities of pentafluorobenzoate (PFB) and 2,4,6-trifluorobenzoate (TFB) leaving groups have been derived from the solvolysis rate constants of X,Y-substituted benzhydryl PFBs and TFBs measured in a series of aqueous solvents, by applying the LFER equation: log k = sf(Ef + Nf). The heterolysis rate constants of dianisylmethyl PFB and TFB, and those determined for 10 more dianisylmethyl benzoates in aqueous ethanol, constitute a set of reference benzoates whose experimental ΔG ? have been correlated with the ΔH? (calculated by PCM quantum-chemical method) of the model epoxy ring formation. Because of the excellent correlation (r = 0.997), the method for calculating the nucleofugalities of substituted benzoate LGs have been established, ultimately providing a method for determination of the SN1 reactivity for any benzoate in a given solvent. Using the ΔG? vs ΔH? correlation, and taking sf based on similarity, the nucleofugality parameters for about 70 benzoates have been determined in 90%, 80%, and 70% aqueous ethanol. The calculated intrinsic barriers for substituted benzoate leaving groups show that substrates producing more stabilized LGs proceed over lower intrinsic barriers. Substituents on the phenyl ring affect the solvolysis rate of benzhydryl benzoates by both field and inductive effects.
Crystallization-induced asymmetric transformation: stereospecific synthesis of L-768,673
Shi, Yao-Jun,Wells, Kenneth M.,Pye, Philip J.,Choi, Woo-Baeg,Churchill, Hywyn R. O.,et al.
, p. 909 - 918 (2007/10/03)
A highly convergent, asymmetric synthesis of L-768,673, an Iks Class III antiarrythmic drug candidate, is described. Synthesis of the racemic 1-trifluoroethyl-3-amino-5-phenyl benzodiazepinone was achieved by Ru-catalyzed hydrogenation of the corresponding oxime that was derived from commercially available 1-trifluoroethyl-5-phenyl benzodiazepine in 76 percent overall yield. An efficient one-pot resolution-racemization of (+/-)-amine provided the desired (+)-amine as its mandelate salt in 92 percent yield and 99.4 percent ee. Regioselective ortho-lithiation of 1,3-bis(trifluoromethyl)benzene with n-BuLi in the presence of a catalytic amount of 2,2',6,6'-tetramethylpiperidine afforded its aryl lithium. Subsequent transmetalation and alkylation with allyl bromide produced the corresponding olefin. Ru-catalyzed oxidative cleavage of the terminated double bond of the olefin provided the desired 2,4-bis(trifluoromethyl)phenylacetic acid in 35 percent overall yield. A modified Schotten-Baumman procedure was developed for coupling of (+)-amine and the acid to produce L-768,673 in 92 percent yield without racemization. - Keywords: Asymmetric synthesis; Benzodiazepines; Oximes; Resolution-racemization
