Tetrakis(dimethylamino)ethylene (TDAE) Mediated Addition of Heterocyclic Difluoromethyl Anions to Heteroaryl Aldehydes. A Facile Synthetic Method for New gem-Difluorinated Alcohols Derived from 4-Bromo-1-naphthylamine and 8-Quinolylamine

Abstract

New heterocyclic-CF 2 CHOH-Ar derivatives, derived from N, N-dimethyl-4-bromo-2-difluoracetyl-1-naphthylamine and N,N-dimethyl-5-difluoroacetyl-8-quinolylamine, are easily obtained in moderate to good yields from the tetrakis(dimethylamino)ethylene (TDAE) mediated reduction of the corresponding -COCF 2 Cl starting materials in the presence of heteroaryl aldehydes.

Copper catalyzed 1,3-dipolar cycloaddition reaction of azides with N-(2-trifluoroacetylaryl)propargylamines

“…N,Ndimethylamino precursors 5 and 9 were found to be the most reactive substrates, while 7 being the less reactive in this series. Benzo [b]thiophene is an important pharmacophore in medicinal chemistry [14] and therefore it was of interest to prepare derivative 17; this substrate was prepared in two steps from the corresponding 15 (Scheme 4), which was in turn prepared in a 60% isolated yield from an original Heck reaction [16] developed in our laboratories, between N,N-dimethyl-4-bromo-1-naphthylamine [15] and benzo [b]thiophene-3-carbonitrile [16]. A moderate 50% isolated yield of 17 was obtained using an excess of propargylamine (3.0 equivalent) in refluxing acetonitrile for 7 h.…”

Nucleophilic difluoromethylation and trifluoromethylation using tetrakis(dimethylamino)ethylene (TDAE) reagent

“…The same group [16b,c] also studied the reactivity of ethyl 3-bromodifluoromethyl-3-benzyloxy-acrylate 29 as a potential CF 2 building block; the TDAE mediated reductive cleavage of 29 in the presence of heteroaryl aldehydes furnished the corresponding d- Not only bromodifluoromethylated heterocyclic substrates were found to be useful starting materials in TDAE mediated reactions; chlorodifluoromethylated ketones are also good partners [17][18][19][20][21][22], and TDAE was found to be useful in generating the corresponding difluoroacetyl anions. The methodology was found to be an alternative and milder approach to the classical Reformatsky reaction [23] that usually requires the use of catalysts or special activation.…”

“…The methodology was found to be an alternative and milder approach to the classical Reformatsky reaction [23] that usually requires the use of catalysts or special activation. Electrophiles that were used with success were heteroaryl aldehydes [17][18][19], a-keto esters [20], N-tosyl aldimines [21] and thiocyanates [13]. Some specific examples are presented in Table 1.…”

Organische Elektronendonoren als leistungsfähige Ein‐Elektronen‐Reduktionsmittel in der organischen Synthese

“…Die TDAE-Methode, die milder als die klassische Reformatsky-Reaktion ist, wurde auf die Herstellung von stabilen a,a-Difluoracetylanionen aus Chlorketonen übertragen. Die Addition an Aldehyde, [70] a-Ketoester [63] und Thiocyanate [64] [73] 4-Dimethylaminopyridinium 81, [74] 1-Methylimidazolium 84 [74] oder Phenylsulfonen 86 [75] .…”