Diastereoselective [3 + 2] cycloaddition of 3-ylideneoxindoles with in situ generated CF₂HCHN₂: syntheses of CF₂H-containing spirooxindoles

Abstract

An efficient [3 + 2] cycloaddition of 3-ylideneoxindoles with in situ generated CFHCHN for the syntheses of spirooxindoles has been developed. This methodology gives access to a range of relatively complex spirooxindoles featuring a CFH group and three contiguous stereogenic centers in up to 84% yield and 99 : 1 trans/cis.

Synthesis and crystal structure of (±)-Ethyl 5′-(difluoromethyl)-2-oxo-4′,5′-dihydrospiro[indoline-3,3′-pyrazole]-4′-carboxylate, C14H13F2N3O3

“…The 4, 5-dihydro-3H-pyrazole ring adopts an envelope conformation with C9 atom deviating by 0.3474(3) Å from the plane formed by C1, C10, N1 and N2 for Mole1, C9A atom deviats by 0.3816(2) Å from the plane formed by C1A, C10A, N1A and N2A for Mole2 [15]. The bond lengths and angles of indolin-2-one and 4,5-dihydro-1H-pyrazole ring are similar to those found in literature [16][17][18]. The indolin-2-one ring and 4,5-dihydro-3Hpyrazole ring form spiro structural feature through their third atom (C1).…”

Difluorodiazoethane (CF2HCHN2): A New Reagent for the Introduction of the Difluoromethyl Group

“…The authors conducted this transformation in different solvents, and demonstrated the compatibility of the in situ preparation of CF 2 HCHN 2 with dichloromethane, chloroform, and acetonitrile. [31] The authors subjected the pyrazoline product to at hermal elimination of nitrogen, which resultedi nf ormation of CHF 2 -spirocyclopropanes (29, 30)i na highly diastereoselective manner.B iological testing of CHF 2 -cyclopropanes with differenth uman cancerc ell lines showed a Scheme5.Dipolar [3+ +2]-cycloadditions of CF 2 HCHN 2 (2)w ith alkynes.…”

“…2019, 25,6053 -6063 www.chemeurj.org marked cytotoxic effect, which was in as imilara ctivity range compared to cis-platin. [32] An interesting reaction was observed by the same authors when switching from dichloromethane to diethyle ther as as olventi na no xygen atmosphere.C F 2 HCHN 2 (2)i nitially underwent dipolar [3+ +2]-cycloaddition to form a pyrazoline that participated in an oxidative [1,5]-sigmatropic rearrangement, followed by a1 ,2-hydrogen shift and dehydrogenationt oy ield pyrazolo[1,5-c]quinazolines (31,32)i ng ood to excellent yields (Scheme8). [33] Recently,W ua nd co-workerss tudied the reactiono fi ns itu generated CF 2 HCHN 2 (2)w ith N-substituted maleimides.…”

“…Han, Chen, and co‐workers further investigated this one‐pot protocol in [3+2]‐cycloaddition reactions of CF 2 HCHN 2 ( 2 ) and 3‐ylideneoxindoles to provide spirocyclic CHF 2 ‐substituted pyrazolines ( 27 , 28 ). The authors conducted this transformation in different solvents, and demonstrated the compatibility of the in situ preparation of CF 2 HCHN 2 with dichloromethane, chloroform, and acetonitrile . The authors subjected the pyrazoline product to a thermal elimination of nitrogen, which resulted in formation of CHF 2 ‐spirocyclopropanes ( 29 , 30 ) in a highly diastereoselective manner.…”

19F‐NMR Diastereotopic Signals in Two N-CHF2 Derivatives of (4S,7R)-7,8,8-Trimethyl-4,5,6,7-tetrahydro-4,7-methano-2H-indazole

“…None of the examples reported in the preceding paragraph concern a chiral molecule containing an N -CHF 2 substituent. There are many examples of azoles bearing a C -CHF 2 substituent, mainly in agrochemistry [ 31 , 32 , 33 ], the field of N -CHF 2 and N -CRF 2 azoles is less studied although there are several articles dealing with the structures presented in Figure 1 .…”