Catalytic Dibenzocyclooctene Synthesis via Cobalt(III)–Carbene Radical and ortho‐Quinodimethane Intermediates

Abstract

The metalloradical activation of ortho‐benzallylaryl N‐tosyl hydrazones with [Co(TPP)] (TPP=tetraphenylporphyrin) as the catalyst enabled the controlled exploitation of the single‐electron reactivity of the redox non‐innocent carbene intermediate. This method offers a novel route to prepare eight‐membered rings, using base metal catalysis to construct a series of unique dibenzocyclooctenes through selective Ccarbene−Caryl cyclization. The desired eight‐membered‐ring products were obtained in good to excellent yields. A large variety of aromatic substituents are tolerated. The proposed reaction mechanism involves intramolecular hydrogen atom transfer (HAT) to CoIII–carbene radical intermediates followed by dissociation of an ortho‐quinodimethane that undergoes 8π cyclization. The mechanism is supported by DFT calculations, and the presence of radical‐type intermediates was confirmed by trapping experiments.

Electrophilic Iron Catalyst Paired with a Lithium Cation Enables Selective Functionalization of Non‐Activated Aliphatic C−H Bonds via Metallocarbene Intermediates

“…In agreement with the above described analysis,repeating the intramolecular CÀHalkylation reaction of 5 catalyzed by 2.5 mol %o f3 and 5mol %o f4,b ut now in presence of 5mol %o fL iAl(OR F ) 4 [OR F = (OC(CF 3 ) 3 ], resulted in enhanced conversions of 5 at 25 8 8C ( Table 2, entries 3a nd 4), with 3 having the highest reactivity and selectivity with a4 8% conversion and a7 2:28 ratio (5a/5b), whereas 4 only rendered a1 8% conversion with a4 7:53 ratio (5a/5b). Seeking to increase the yield of 5a,weoptimized the loading of the lithium salt LiAl(OR F ) 4 (entries 5-9), resulting in nearly quantitative conversion of 5,with the best 5a/5b ratio and ah igh 5a diastereomeric ratio (76/24, syn:anti)a t 25 mol %c oncentration (entry 6).…”

“…This scenario is reminiscent to the one recently reported for the C(sp 2 ) À Hb ond alkylation reactions via non-heme iron-carbene species.I nt his case, computational studies rationalize the high reaction temperatures (80 8 8C) required for dissociation of an unproductive Fe-O(C) adduct formed between the iron catalyst and the oxygen atom of the carbonyl group of ethyl diazoacetate. Further evidence for the strong binding of 5 to lithium is provided by mass spectroscopy analysis of areaction mixture of 5 and LiAl(OR F ) 4 (1:0.25), which exhibits peaks at m/z = 471.2585 and 239.1384, corresponding to am ono-and bis-adduct between 5 and the lithium cation (see Figures S129-S131). According to this assignation, the intensity of the free diazo band systematically decreased to depletion in favor of the adduct band as the concentration range of LiAl(OR F ) 4 increased from 5t o2 5mol %.…”

“…These observations suggest that the iron compound is unable to effect formation of the metallocarbene intermediate upon nitrogen release of the diazo compound, and instead an ovel adduct species through the binding of the Odonor atom of the carbonyl group [Fe-O(C)],present in the diazo reagent, to the Lewis acid Fe II of 3 is formed. In solution, ad ynamic binding of lithium to 5 can be deduced by 1 HNMR study of the previously described reaction mixtures within the concentration range 5-25 mol %ofLiAl(OR F ) 4 ,which display only one set of broad signals of the diazoester reagent (see Fig-ures S127-S128 in the Supporting Information). [7a] We hypothesized that the undesired Fe-O(C) interaction can be disfavored by addition of as tronger Lewis acid than the iron centers present in 3 and 4.I ndeed, by repeating the infrared spectroscopy of the mixture formed by 5 and variable amounts of the lithium salt LiAl(OR F ) 4 [OR F = (OC(CF 3 ) 3 ] (5-25 mol %), we observed as plit in two of the investigated C = Obands assigned to free 5 (1690 cm À1 )and lithium-bound 5 (1654 cm À1 ;Figures 2d-f).…”

“…Among the different existing strategies, [1] thef ormal metalmediated insertion of carbene fragments into C(sp 3 )ÀH bonds [2] is an appealing methodology because of its greater atom economy when compared with the most extended crosscoupling procedures,e mploying organometallic coupling partners (boron, zinc,o rG rignard reagents). [4] In contrast, iron systems,which are attractive from asustainability perspective, [5] have shown modest activity and are limited to less demanding processes,i ncluding cyclopropanation reactions, [6] and alkylation of C(sp 2 )ÀH, [7] heteroatom-hydrogen, [8] and relatively weak allylic and benzylic (BDE < 90 Kcal mol À1 )C (sp 3 )ÀH bonds (Scheme 1). [4] In contrast, iron systems,which are attractive from asustainability perspective, [5] have shown modest activity and are limited to less demanding processes,i ncluding cyclopropanation reactions, [6] and alkylation of C(sp 2 )ÀH, [7] heteroatom-hydrogen, [8] and relatively weak allylic and benzylic (BDE < 90 Kcal mol À1 )C (sp 3 )ÀH bonds (Scheme 1).…”

[Co(TPP)]‐Catalyzed Formation of Substituted Piperidines

“…This type of reactivity belongs to a more general class of catalytic reactions involving single‐electron elementary steps, called metalloradical catalysis . Cobalt(III)‐carbene radical chemistry has been successfully applied in the synthesis of carbo‐ and heterocyclic structures, including cyclopropanes, chromenes, furans, indenes, indolines, ketenes, butadienes and dihydronaphthalenes, dibenzocyclooctenes, as well as phenylindolizines . Recently, the group of Zhang reported the synthesis of chiral pyrrolidines and related five‐membered ring compounds, starting from N‐tosylhydrazone derivatives and catalyzed by cobalt(II) complexes of D 2 ‐symmetric chiral amidoporphyrins (Scheme A) .…”