Divergent Titanium‐Mediated Allylations with Modulation by Nickel or Palladium

Abstract

Titanocene(III)-mediated radical processes are important tools for the formation of CÀC bonds under mild conditions, and are compatible with many functional groups. [1,2] Moreover, titanium(III) complexes can be used substoichiometrically, [3] which has allowed the development of enantioselective versions of these reactions. [4] A serious limitation of these radical processes, however, derives from the fact that titanium(III)-mediated radical generation requires reactive substrates, such as allylic halides, which are often cumbersome in introduction and manipulation. Allylic carbonates and carboxylates, in contrast, are easily prepared and handled but are inert against titanocene-(III) complexes. Nevertheless, it is known that nickel and palladium complexes can readily activate allylic carbonates and carboxylates I (Scheme 1) to form h 3 -allylmetal complexes (II). On the basis of these results, we deemed that the combination of palladium or nickel derivatives with titanocene(III) complexes would facilitate the development of novel allylation processes using accessible allyl carbonates or carboxylates.In the case of palladium catalysis, it is known that the Oppolzer-type cyclization of organometallic species (II, M = Pd, Scheme 1) to cyclic derivatives (VI) is relatively slow at room temperature.[5] Thus, reduction of II by a singleelectron-transfer reagent, such as [Cp 2 TiCl], [6] could lead to the allylic radical III, which might be eventually trapped by a second [Cp 2 TiCl] species to give an allylic titanium(IV) complex IV. Finally, nucleophilic attack of the organometallic derivative IV on an aldehyde or other electrophilic reagent would provide the corresponding allylation product V.On the other hand, nickel-catalyzed carbocyclizations, via intermediates such as II (M = Ni, Scheme 1) to cyclic derivatives VI, are relatively fast at room temperature. [7] Once formed, VI might be reduced by [Cp 2 TiCl] to a primary radical VII, which could be trapped by a second [Cp 2 TiCl] species to give an alkyl titanium(IV) complex VIII. Hydrolysis of the organometallic derivative VIII would yield carbocycles IX. Thus, we anticipated that the use of palladium or nickel catalysts could modulate titanium(III) to drive allylation reactions with allyl carboxylates by two different pathways, either through intermolecular coupling with electrophilic reagents or to give carbocyclic derivatives by an intramolecular allylation.To check our hypothesis, we chose allylic carbonate E-1 as a model allylation reagent. Thus, reaction of decanal with carbonate E-1 and an excess of [Cp 2 TiCl] (2.0 equiv), [8] in the presence of PdCl 2 (20 mol %) and triphenylphosphine, [9] gave the expected coupling product 2 as a single stereoisomer in 76 % yield (Scheme 2).[10] In contrast, when carbonate E-1 was treated with an excess of [Cp 2 TiCl] (2.0 equiv) in the presence of [NiCl 2 (PPh 3 ) 2 ] (20 mol %), a mixture of carbocycles 3 and 4 (4:1 ratio) was obtained in almost quantitative Scheme 1. Mechanism for palladium-catalyzed, titanocene-medi...

Redox‐Neutral α‐Allylation of Amines by Combining Palladium Catalysis and Visible‐Light Photoredox Catalysis

“…2 In contrast, reversal of reactivity of the π‐allylpalladium complex can be realized through two‐electron3 or single‐electron reduction4 (Scheme , paths 2 and 3) in the presence of stoichiometric amounts of reducing reagents (e.g., Et 3 B, Et 2 Zn, InI, SmI 2 , or Mn powder). The resultant allylic metal complex (η 1 ‐type) or allylic radical enables the nucleophilic addition to aldehydes, ketones, and imines,3 as well as radical homocoupling4a,d and intramolecular radical addition reactions 4b–d. Despite the advances, the catalytic generation of an allylic radical from a π‐allylpalladium complex without additional reductants remains a challenge.…”

Metal‐Catalyzed β‐Functionalization of Michael Acceptors through Reductive Radical Addition Reactions

“…Thep erformance of the catalyst can be tailored by fine-tuning ligand properties, [24] and catalysis by [Cp 2 TiCl] is compatible with catalysis by latetransition metals. [26] Finally,e poxides of chalcones and related aryl ketones have been reductively opened through photoredox catalysis. As recent reports show (see also Section 2.4), reactions combining [Cp 2 TiCl] with Ni or Pd catalysis can also be realized.…”

“…As recent reports show (see also Section 2.4), reactions combining [Cp 2 TiCl] with Ni or Pd catalysis can also be realized. [26] Finally,e poxides of chalcones and related aryl ketones have been reductively opened through photoredox catalysis. [27] Theu se of Hantzsch esters and Michael acceptors resulted in the addition products being obtained.…”

Mixed disproportionation versus radical trapping in titanocene(III)-promoted epoxide openings

“…2 It has been used in many interesting transformations, such as the homolytic ring opening of epoxides, 3 the radical cascade cyclization of epoxypolyenes, 4 Michael-type coupling between aldehydes and conjugated alkenals, 5 pinacol coupling reactions, 6 H-atom transfer from water to free radicals, 7 alkenes and alkynes, 8 divergent C-C bondforming reactions with modulation by Ni or Pd, 9 metal-catalyzed Barbier-type cyclizations and a-prenylation of carbonyl derivatives, 10 and the Reformastky-type addition of a-haloketones to carbonyl compounds. 11 Interestingly, during the last few years new developments in titanocene-regenerating agents have led to many transformations being carried out using only 5-20 mol % of titanium catalyst.…”