Zinc Tetrafluoroborate Hydrate as a Mild Catalyst for Epoxide Ring Opening with Amines: Scope and Limitations of Metal Tetrafluoroborates and Applications in the Synthesis of Antihypertensive Drugs (RS)/(R)/(S)-Metoprolols

Abstract

The scope and limitations of metal tetrafluoroborates have been studied for epoxide ring-opening reaction with amines, and Zn(BF(4))(2)·xH(2)O has been found to be a mild and efficient catalyst affording high yields under solvent-free conditions at rt with excellent chemo-, regio-, and stereoselectivities. The catalytic efficiency followed the order Zn(BF(4))(2)·xH(2)O ≫ Cu(BF(4))(2)·xH(2)O > Co(BF(4))(2)·6H(2)O ≫ Fe(BF(4))(2)·6H(2)O > LiBF(4) for reactions with cyclohexene oxide and Zn(BF(4))(2)·xH(2)O ≫ Co(BF(4))(2)·6H(2)O ≫ Fe(BF(4))(2)·6H(2)O > Cu(BF(4))(2)·xH(2)O for stilbene oxide, but AgBF(4) was ineffective. For reaction of styrene oxide with aniline, the metal tetrafluoroborates exhibited comparable regioselectivity (1:99-7:93) with preferential reaction at the benzylic carbon of the epoxide ring. A reversal of regioselectivity (91:1-69:31) in favor of the reaction at the terminal carbon of the epoxide ring was observed for reaction with morpholine. The regioselectivity was dependent on the electronic and steric factors of the epoxide and the pK(a) of the amine and independent of amine nucleophilicity. The role of the metal tetrafluoroborates is envisaged as "electrophile nucleophile dual activation" through cooperativity of coordination, charge-charge interaction, and hydrogen-bond formation that rationalizes the catalytic efficiency, substrate reactivity, and regioselectivity. The methodology was used for synthesis of cardiovascular drug metoprolol as racemic and enriched enantiomeric forms.

An evaluation of the CYP2D6 and CYP3A4 inhibition potential of metoprolol metabolites and their contribution to drug–drug and drug–herb interaction by LC‐ESI/MS/MS

“…A description of synthesis procedure of DIM metabolite is given in the Supporting Information (Pujala et al, 2011;Zhang et al, 2008). The ClogP value of DIM was 0.32 and it is less lipophilic than MET.…”

Graphite oxide catalyzed synthesis of $\beta $-amino alcohols by ring-opening of epoxides

“…The ring-opening reaction of epoxides with amines under solvent-free conditions has also been investigated in several reports. 11,18,19 Nevertheless, many of these methodologies suffer from one or more disadvantages such as elevated temperatures, long reaction times, high pressure, moderate yields, requirement of stoichiometric amounts of catalyst, use of air and moisture sensitive catalysts, and hazardous organic solvents. The various catalysts and experimental conditions used are summarized in Table 1. 13,14,20−27 Therefore, further efforts are required for aminolysis of epoxides with amines.…”

N-functionalized L-proline anchored MCM-41: A novel organic–inorganic hybrid material for solvent-free aminolysis of styrene oxide under microwave irradiation

“…8 Aminolysis of epoxides is an acid-catalyzed reaction. Among the catalysts reported for this type of reaction, Lewis acid catalysis is the most widely adopted method for epoxide ring openings with amines, e.g., BiCl 3 16 Therefore, the search for new environmentally friendly, atom-efficient methods, which avoid the use of large amounts of condensing reagents, and activators should be beneficial and drawn increasing interest. Among heterogeneous catalysts used for the synthesis of β-amino alcohols, SBA-15-pr-SO 3 H, 17 mesoporous aluminosilicate, 18 Ti-MCM-41, 19 zeolite NaY, 20 Fe-Zn cyanide complex, 21 cobalt complex/SBA-15,…”