Efficient One‐Pot Reductive Aminations of Carbonyl Compounds with Aquivion‐Fe as a Recyclable Catalyst and Sodium Borohydride

Abstract

A one-pot reductive amination of aldehydes and ketones with NaBH 4 was developed with a view to providing efficient, economical and greener synthetic conditions. A recyclable iron-based Lewis catalyst, Aquivion-Fe, was used to promote imine formation in cyclopentyl methyl ether, followed by the addition of a small amount of methanol to the reaction mixture to enable C=N reduction by NaBH 4 . The protocol, applied to a wide number of amines and carbonyl compounds, resulted in [a]

Modifications at C(5) of 2-(2-Pyrrolidinyl)-Substituted 1,4-Benzodioxane Elicit Potent α4β2 Nicotinic Acetylcholine Receptor Partial Agonism with High Selectivity over the α3β4 Subtype

“…The hydroxyl function was mesylated and the amine function was deprotected to give ( S , S )- 17a , ( S , S )- 17b , and ( S , S )- 17c and their epimers ( S , R )- 17a , ( S , R )- 17b , and ( S , R )- 17c . The subsequent cyclization of the three S , S stereoisomers by internal SN2 reaction afforded the pyrrolidinyl benzodioxanes ( S , R )- 18a , ( S , R )- 18b , and ( S , R )- 18c , which were N -methylated to the final products ( S , R )- 2a , ( S , R )- 2b , and ( S , R )- 2c with formaldehyde and NaBH 4 using Aquivion-Fe as a catalyst in the green ether CPME. , Identically, ( S , R )- 17a , ( S , R )- 17b , and ( S , R )- 17c were cyclized to ( S , S )- 18a , ( S , S )- 18b , and ( S , S )- 18c and then N -methylated to give ( S , S )- 2a , ( S , S )- 2b , and ( S , S )- 2c .…”

“…The subsequent cyclization of the three S,S stereoisomers by internal SN2 reaction afforded the pyrrolidinyl benzodioxanes (S,R)-18a, (S,R)-18b, and (S,R)-18c, which were N-methylated to the final products (S,R)-2a, (S,R)-2b, and (S,R)-2c with formaldehyde and NaBH 4 using Aquivion-Fe as a catalyst in the green ether CPME. 32,33 Identically, (S,R)-17a, (S,R)-17b, and (S,R)-17c were cyclized to (S,S)-18a, (S,S)-18b, and (S,S)-18c and then N-methylated to give (S,S)-2a, (S,S)-2b, and (S,S)-2c. N-Acetylation of (S,R)-1a and (S,S)-1a with acetyl chloride at room temperature in DCM afforded (S,R)-5a and (S,S)-5a, respectively.…”

“…The affinities (K i ) of the synthetized compounds for the α4β2, α3β4, and α7 receptors were determined using [ 3 H]epibatidine (specific activity of 56−60 Ci/ mmol; PerkinElmer, Boston, MA)-labeled rat cerebral cortex membranes (α4β2) or membranes of HEK 243 cells stably transfected with human α3β4 nAChR and [ 125 I]α-bungarotoxin (specific activity of 200−213 Ci/mmol, PerkinElmer, Boston, MA)labeled rat hippocampus membranes (α7), as previously described. 29,32 The K d and K i values were derived from three [ 3 H]epibatidine and [ 125 I]α-bungarotoxin saturation and three competition binding experiments using rat cortex (α4β2) and hippocampus (α7) membranes and the membrane of human α3β4transfected cells. 29,35 Briefly, for saturation experiments, the membrane homogenate aliquots were incubated overnight at 4 °C with 0.01−2.5 nM concentrations of [ 3 H]epibatidine.…”

Improved Process for the Synthesis of 3-(3-Trifluoromethylphenyl)propanal for More Sustainable Production of Cinacalcet HCl

“…Recently, an improved alternative protocol of reduction amination, avoiding the use of hydrogen and employing NaBH 4 in the presence of the recyclable heterogeneous greener Lewis acid Aquivion ® -Fe, has been described by some researchers [ 25 ]. This procedure is very suitable when hydrogen is not available or it is preferable not to use it.…”

Efficient conversion of d-mannitol into 1,2:5,6-diacetonide with Aquivion-H as a recyclable catalyst

“…In terms of sustainability, the catalytic approach is superior and, in the present case, an additional attractive feature could be a heterogeneous catalysis with the recyclable solid catalyst we intended to use. This was Aquivion-H (Figure 3), a commercially available perfluorosulfonic ionomer (Aquivion PW87S), possessing superacid character, used to prepare polymer electrolyte membranes [33], whose iron-salt we have recently reported as an efficient recyclable catalyst of one-pot reductive aminations [34,35].…”