Production of Csp³–Csp³ Bonds through Palladium‐Catalyzed Tsuji–Trost‐Type Reactions of (Hetero)Benzylic Substrates

Abstract

This review covers the formation of Csp 3 -Csp 3 bonds through Pd-catalyzed reactions of benzylic and heterobenzylic substrates bearing acetate, carbonate, phosphonate, or halide leaving groups, with malonate-type compounds, oxazoles, aldehydes, α, -unsaturated aldehydes, oxindoles, or azlactones. Some of these coupling reactions have been carried out efficiently under enantioselective conditions. In most cases the reaction involves nucleophilic addition to the η 3 -benzylpalladium intermediate formed by elimination of the leaving group. Before

Enantioselective α‐Benzylation of Acyclic Esters Using π‐Extended Electrophiles

“…Despite possessing isostructural and isoelectronic characteristics, asymmetric Pd-catalyzed benzylic alkylation reactions using enolate nucleophiles are far less common. [2] This is attributable, in part, to the difficulty in forming Pd 0 /arene complexes and the relatively high energy required for dearomatizing ionization/oxidative addition (Figure 1 a). …”

“…[14] Whereas π-extended electrophiles functioned effectively, simple monocyclic benzylic phosphates were unreactive, presumably owing to the aforementioned energy required for dearomatization. [2–6] Pfp esters derived from alkylacetic acids are also unreactive within this cooperative catalysis framework.…”

C–O Bonds from Pd‐Catalyzed C(sp3)–H Reactions Mediated by Heteroatomic Groups

“…[22] Whereas oxidative deoximation also occurred in AcOH [Equation (7)], [35] the main reaction in a 1:1 mixture of AcOH and Ac 2 O at 100°C was acetoxylation of the -primary carbon center and acetylation of the hydroxy group [Equation (8)]. [36] In fact, O-acetylation of oximes happens at room temperature in AcOH/Ac 2 Ohence the adoption of a one-pot, two-step procedure [Equations (9) and (10)], [22] notably for the preparation of an intermediate of the synthesis of jiadifenolide [Equation (11)]. [37] The Pd(OAc) 2 /PhI(OAc) 2 /AcOH/Ac 2 O procedure has been used for acetoxylation of the O-benzyl and O-methyl oximes shown in Equations (12) and (13), in steps towards the total synthesis of paspaline [Equation (12)] [38] and oridamycins [Equation (13)].…”

“…Benzyl acetate would be formed from 2A and AcOH either through nucleophilic attack on the benzylic carbon (path b) or through ligand exchange leading to 2B and subsequent reductive elimination (path c). [9] Scheme 2. That would promote the subsequent interaction with the methyl group leading to η 3 -benzylpalladium 2D.…”

Palladium‐Catalyzed Suzuki–Miyaura Cross‐Coupling of Secondary α‐(Trifluoromethyl)benzyl Tosylates

“…[16][17][18] Thei ntermediate Pd II species could be readily functionalized to give ar ange of products bearing as tereogenic trifluoromethylated center. [16][17][18] Thei ntermediate Pd II species could be readily functionalized to give ar ange of products bearing as tereogenic trifluoromethylated center.…”