Tandem Aza Michael Addition–Vinylogous Nitroaldol Condensation: Construction of Highly Substituted N-Fused 3-Nitropyrazolopyridines

Abstract

A base-mediated tandem aza-Michael addition-vinylogous nitroaldol condensation has been described between 3,5-dialkyl 4-nitropyrazoles and alkynyl ketones/aldehydes. This transition metal-free atom economical transformation occurred via C-N and C═C bond formations in one step with the elimination of water. The construction of a variety of highly substituted N-fused 3-nitropyrazolopyridine derivatives has been demonstrated with good yields. Good to excellent regioselectivities have been achieved with unsymmetrically substituted 4-nitropyrazoles.

Synthesis of trifluoromethyl or trifluoroacetyl substituted heterocyclic compounds from trifluoromethyl‐α,β‐ynones

“…From 2015 to 2019, the regioselectivity of the cyclocondensation of trifluoromethyl‐α,β‐ynones 3 or 3a ‐ c with hydrazines 19 or hydrazine hydrochlorides 22 , hydroxylamine, or 3,5‐dimethyl‐4‐nitropyrazole 30 being readily tuned to afford trifluoromethyl‐pyrazoles 20 , 21 , 24 , 28, or 29 , trifluoromethyl‐isoxazole 26, and trifluoromethyl‐pyrazolo[1,5‐ a ]pyridine 31 was developed by the groups of Hsieh, Nenajdenko, Grygorenko, and Suresh (Scheme 8). [ 13,45–50 ] The reactions between ynones 3 and hydrazines 19 in DMSO at 110°C, [ 45 ] in CH 2 Cl 2 catalyzed by Cu(OAc) 2 , [ 45 ] in hexafluoroisopropanol (HFIP) at 7°C to room temperature, [ 46 ] or in CHCl 3 catalyzed by AgOTf, [ 47 ] delivered the target products 20 and 21 in good to excellent yields (Hsieh's group: 82–95% yields of 20 , 78–95% yields of 21 ; Nenajdenko's group: 73–99% yields of 20 and 21 mixture, 87–99% yields of 21 ). Hydrazine hydrochlorides 22 reacted with ynones 3 in DMSO at room temperature or in EtOH at 60–65°C accompanied by dehydration to form hydrazones 23 , which can further afford 66–99% yields of 3‐CF 3 ‐pyrazoles 21 or 87–100% yields of 4‐iodo‐3‐CF 3 ‐pyrazoles 24 in the presence of NaOH, t ‐BuOK, or DBU as base, or I 2 and NaHCO 3 in CH 3 CN at room temperature for 24 hr.…”

Reactions of Trifluoroacetyl Alkynes Under Electrophilic Activation with Brønsted Acids or Acidic Zeolites

“…In this case, indene 5a was isolated in 54 % yield (entry 1). The reaction of other alkynes 1b,j,k with benzene under the action of zeolite CBV-720 afforded the corresponding indenes 5c-e in up to 81 % yield (entries 6,7,9). The same reactions in TfOH resulted in the formation of the indenes in lower yields of 36-40 % (entries 8, 10).…”

“…[1][2][3][4][5][6][7] Among all other fluorinated organic compounds, trifluoroacetyl alkynes bearing two synthetically important functional groups, acetylene and carbonyl ones, are versatile building blocks for the synthesis of various trifluoromethyl substituted O-, N-, or S-heterocycles, and many other compounds. [8][9][10][11][12][13][14][15] Moreover, these acetylenes have highly polarized triple bond, since the trifluoroacetyl group is one of the most strong electron withdrawing groups.…”

Trifluoromethylated 3‐(Pyrazol‐1‐yl)propanamide (PPA) Ligands

“…The starting materials 3‐methyl‐5‐(trifluoromethyl)‐1 H ‐pyrazole ( 1 ) [21] and 3,5‐bis(trifluoromethyl)‐1 H ‐pyrazole ( 2 ) [22] were obtained by a standard method, treating the corresponding 1,3‐diketones with hydrazine ( Scheme 1). Subsequent reaction of 1 and 2 with acrylamide following a standard protocol [14] afforded the new 3‐pyrazolylpropanamides CF 3 MePPA ( 3 ) and (CF 3 ) 2 PPA ( 4 ).…”