Unusual Chemoselective Rh^II‐Catalysed Transformations of α‐Diazocarbonyl Piperidine Cores

Abstract

The reactivity of various α-diazocarbonyl piperidine scaffolds, characterised by an increased molecular complexity, was tested with various Rh(II) catalysts. The structure of the starting reagent is of relevance to the synthetic results. An unexpected dimerisation took place, starting from the simple piperidine scaffold, to give the hexahydrotetrazine ring system. Products derived from a nitrogen ylide intermediate or aromatic substitution (1,3,4,5-tetrahydro-2,5-methanobenzo[c]azepine and 1,2,3,3a-tetrahydrocyclopenta[de]isoquinolin-4(5 H)-one rings, respectively) were obtained from tetrahydroisoquinoline derivatives. The chemoselectivity of the reaction could be controlled by the choice of starting reagent, Rh(II) catalyst and the reaction conditions. Finally, it was found that the azepino heterocycle could coordinate to the catalyst to give new Rh(II) complexes.

New sp3 diphosphine-based rhodium catalysts for the asymmetric conjugate addition of aryl boronic acids to 3-azaarylpropenones

“…From our point of view, despite lower values in terms of enantioselectivity and reaction rate, the results with L6, a diphosphine with only the sp 3 Surprisingly, for substrate 1 the results obtained using L8 as ligand were better in terms of enantioselectivity in comparison with those obtained with (R,R)-ZEDPHOS, (R,R)-Xylyl-ZEDPHOS and (R,R)-Xylyl-EPHOS as reported in Table 2 (entry 5 versus entries 1, 3 and 8), leading to product 1a in a remarkable 94% e.e. in THF and 84% e.e in IPA.…”

“…Conversely, the addition of phenylboronic acid was evaluated for four different 3-azaarylpropenones as substrates, hereafter called 1 ((E)-1-phenyl-3-(pyridin-2-yl)prop-2-en-1-one), 2 ((E)-1-phenyl-3- and 4 ((E)-3-(1-methyl-1H-imidazol-4-yl)-1-phenylprop-2-en-1-one) respectively. 26 In order to get a prognostic insight into the reactivity of different rhodium based catalytic systems in this type of reaction, we employed diphophine ligands characterized by varied types of chirality: phosphorus based ligands bearing only an atropoisomeric chirality as in (S)-TetraMe-BITIANP (L1) and (S)-BITIANP (L2), 23,27 ; diphosphines endowed with a mixed chirality (both sp 3 and atropoisomeric) as in (S,S,Sax)-DIOPHEP (L3) 28 and (R,Rax)-ISAPHOS C1 (L4) and (S,Rax,Rax)-ISAPHOS C2 (L5) 29,30 ; or only a sp 3 chirality as in the case of (R,R)-ZEDPHOS (L6). 20 Table 1.…”

“…2 Enantioselective catalysis using metal complexes provides one of the most general and flexible methods for the synthesis of chiral compounds. 3,4 In these regards, the proper combination of the selected metal with the correctly designed enantiopure ligand is the determining step for obtaining synthetic processes with high efficiency. Indeed, this provides the ideal way to multiply chirality affording large amounts of chiral products of either absolute configuration exploiting only small quantity of chiral source.…”

Asymmetric Hydrogenation vs Transfer Hydrogenation in the Reduction of Cyclic Imines

“…These diphosphines are derived from the condensation of the thiophene ring, like TetraMe‐BITIANP, BITIANP and TetraMe‐BITIOP . The two 3,4‐disubstituted isoquinolines were chosen considering the possible application of the corresponding tetrahydroquinolines as unnatural β‐aminoacids and considering that in the case of substrate A , a biocatalytic resolution of the corresponding amines is easy to realize conversely to the more difficult of derivative B ,…”

Tandem Tetrahydroisoquinoline‐4‐carboxylic Acid/β‐Alanine as a New Construct Able To Induce a Flexible Turn

“…An oily residue was obtained that corresponded to acid (+)‐ 6 (823 mg, 60 %, ≈48 % ee ). NMR spectroscopy data for compound 6 were in agreement with those reported in the literature …”