Mono- and Dialkyne Insertion Reactions of Cyclopalladated N,N′,N″-Triarylguanidines [κ²(C,N)Pd(μ-Br)]₂ and cis-/trans-[κ²(C,N)Pd(Lewis Base)Br]. Scaffolds for Enlarged, Rearranged, and Zwitterionic Palladacycles through Ring Contraction cum Amine–Imine Tautomerization

Abstract

Insertion reactions of six-membered cyclopalladated N,N′,N″-triarylguanidines, [κ 2 (C,N)Pd(μ-Br)] 2 (III−V), with various alkynes in CH 2 Cl 2 under ambient conditions afforded diinserted eight-membered palladacycles, [(κ 2 (C,N):η 2 (CC)-PdBr] (1−11), in high yield (76−96%), while insertion reactions of six-membered cyclopalladated N,N′,N″-triarylguanidines, [κ 2 (C,N)Pd(Lewis base)Br] (VI− XI), with various alkynes under the aforementioned conditions afforded monoinserted six-membered palladacycles, [κ 2 (C,N)-Pd(Lewis base)Br] (12−21), in high yield (81−91%) except for 14 (23%). The insertion reaction of VI with 2 equiv of dimethyl acetylenedicarboxylate (DMAD) and the insertion reaction of 12 with 1 equiv of DMAD in CH 2 Cl 2 under ambient conditions resulted in the formation of a diinserted zwitterionic fivemembered palladacycle, [κ 2 (C,C)Pd(2,6-lutidine)Br] (22), in 76% and 70% yields, respectively. Palladacycle 22 upon reaction with AgOTf in wet MeCN afforded the ionic palladacycle [κ 2 (C,C)Pd(2,6-lutidine)(H 2 O)][OTf] (23) in 78% yield. The ring size of the "[κ 2 (C,N)Pd]" unit in the structurally characterized diinserted palladacycles (1•2CH 2 Cl 2 •H 2 O, 2, 5, and 7), and monoinserted palladacycles (17, 18, and 20•C 7 H 8 •H 2 O) is smaller than that anticipated for mono-and diinserted palladacycles, and this feature is mainly ascribed to the proclivity of III−XI to undergo ring contraction cum amine−imine tautomerization upon alkyne insertion. Palladacycle 22 represents the first diinserted product obtained in alkyne insertion reactions of [κ 2 (C,N)Pd(Lewis base)X] type palladacycles. The molecular structure of 22•H 2 O determined by X-ray diffraction indicates that the positive charge on the guanidinium moiety is balanced by the negative charge on the palladium atom and thus represents the first structurally characterized zwitterionic palladacycle to be reported in alkyne insertion chemistry. Plausible mechanisms of formation of 12−21 and 22 have been outlined. The presence of more than one species in solution for some of the palladacycles in the series 1−7 and 12−21 was explained by invoking the C−N single-bond rotation of the CN 3 unit of the guanidine moiety, while this process in conjunction with Pd−N(lutidine) bond rotation was invoked to explain the presence of four isomers of 15, as studied with the aid of variable-concentration 1 H NMR experiments carried out for 14 and 15.

Depalladation of Neutral Monoalkyne- and Dialkyne-Inserted Palladacycles and Alkyne Insertion/Depalladation Reactions of Cationic Palladacycles Derived from N,N′,N″-Triarylguanidines as Facile Routes for Guanidine-Containing Heterocycles/Carbocycles: Synthetic, Structural, and Mechanistic Aspects

“…The formation of 1 involves C–N bond formation through nucleophilic attack of the imino nitrogen atom on the palladated carbon followed by reductive elimination of palladium in the form of Pd 0 L accompanied by the loss of HBr. Oxidative addition of HBr to Pd 0 L species could form “PdHBr(L)” species, and this hydrido species subsequently recombines with itself to form trans -[L 2 PdBr 2 ] (L = 2,6-Me 2 C 5 H 3 N), Pd(0), and H 2 , as discussed by Vicente and co-workers and subsequently by us . The formation of 2 from II is believed to occur in two steps, as shown in Scheme .…”

“…Palladacycle 6 undergoes an insertion reaction with DPA to afford the eight-membered palladacyclic intermediate N , which upon ring contraction followed by amine–imine tautomerization can give rise to the intermediate O . Ring contraction and amine–imine tautomerization or only amine–imine tautomerization is frequently invoked to explain the formation of small molecule inserted products in stoichiometric − , and catalyzed reactions mediated by palladium. In the past, we have isolated palladacycles such as I and II , which are neutral analogues of O , from the monoalkyne insertion reactions of six-membered cyclopalladated guanidines, cis- / trans -[( C , N )PdBrL] .…”

“…Ring contraction and amine–imine tautomerization or only amine–imine tautomerization is frequently invoked to explain the formation of small molecule inserted products in stoichiometric − , and catalyzed reactions mediated by palladium. In the past, we have isolated palladacycles such as I and II , which are neutral analogues of O , from the monoalkyne insertion reactions of six-membered cyclopalladated guanidines, cis- / trans -[( C , N )PdBrL] . The intermediate O upon insertion with a second molecule of DPA can give rise to the intermediate P .…”

“…Recently, we studied alkyne insertion reactions of cyclopalladated guanidines of the types [κ 2 ( C , N )Pd(μ-Br)] 2 and [κ 2 ( C , N )Pd(Lewis base)Br] to afford a variety of alkyne-inserted palladacycles with unanticipated frameworks, mainly due to ring contraction cum amine–imine tautomerization of alkyne-inserted palladacyclic intermediates in conjunction with the nature of the alkyne, coordinated anion, and other reaction conditions. , We have chosen the monoalkyne- and dialkyne-inserted cyclopalladated guanidines I – III for depalladation reactions following the first route, as such an attempt would afford guanidine-containing heterocycles/carbocycles (see Chart ) . We have also used the cyclopalladated guanidines IV and V as starting materials for more reactive substrates of the type [κ 2 ( C , N )PdL 2 ] + [WCA] − , which would enable us to isolate guanidine-containing hetero- and carbocycles through the second route, as outlined above (see Chart ). , Nitrogen-containing heterocycles are medicinally important compounds, and more importantly, guanidine-containing heterocycles are considered as privileged scaffolds in heterocyclic chemistry. , Line drawings of a few medicinally important guanidine-containing heterocycles are shown in Chart . , Herein, we report the synthesis and characterization of three new cationic cyclopalladated guanidines, four new heterocycles, and one carbocycle.…”

Direct Observation of C–H Cyclopalladation at Tertiary Positions Enabled by an Exo-Directing Group

“…Though uncommon, tertiary alkyl palladium complexes have been prepared via three approaches: (1) transmetalation with an acidic carbon nucleophile, (2) cyclometalation with alkylidenecyclopropanes, and (3) alkyl group migration . Direct C–H cyclopalladation at tertiary positions has not been directly observed.…”