Enantioselective Palladium‐Catalyzed Insertion of α‐Aryl‐α‐diazoacetates into the OH Bonds of Phenols

Abstract

A palladium-catalyzed asymmetric O À H insertion reaction was developed. Palladium complexes with chiral spiro bisoxazoline ligands promoted the insertion of a-aryl-adiazoacetates into the OÀH bond of phenols with high yield and excellent enantioselectivity under mild reaction conditions. This palladium-catalyzed asymmetric O À H insertion reaction provided an efficient and highly enantioselective method for the preparation of synthetically useful optically active a-aryl-aaryloxyacetates.Palladium is an indispensable and versatile catalyst in modern organic synthesis.[1] Palladium efficiently catalyzes the cyclopropanation of olefins with diazomethane, a widely used carbene-transfer reaction, [2] and various new palladiumcatalyzed carbene-transfer reactions based on migratory insertion have recently been developed.[3] However, asymmetric palladium-catalyzed carbene-transfer reactions are rare and remain a challenge. The early examples of palladium-catalyzed asymmetric carbene-transfer reactions involved cyclopropanations and carbenylative amination, however, the resulting enantioselectivity was unsatisfactory. [4] Recently, Hu and co-workers [5] reported highly enantioselective palladium-catalyzed three-component reactions of pyrrole, diazoesters, and imines. Herein, we report a palladiumcatalyzed asymmetric insertion of a-aryl-a-diazoacetates into the O À H bond of phenols (Scheme 1).[6] Palladium complexes with chiral spiro bisoxazoline ligands efficiently catalyzed the OÀH insertion reaction, which provides a new method for the preparation of a-aryl-a-aryloxyacetates 3 with good yields and excellent enantioselectivity under mild, neutral reaction conditions.The a-aryl-a-aryloxyacetate moiety is ubiquitous in biologically active molecules [7] and it is also present in a chiral solvating agent for NMR spectroscopy [8] (Scheme 1). The established methodologies for the synthesis of optically active a-aryl-a-aryloxyacetates are based on either multistep transformations from chiral starting materials or the use of chiral auxiliaries. [7,8] To our knowledge, no highly enantioselective catalytic asymmetric method for preparing these important compounds has been reported. [9] The challenges lie mainly in the high acidity of the ahydrogen of a-aryl-a-aryloxyacetates. Because these compounds readily epimerize under basic conditions or at high temperature, any reliable method for their preparation should involve mild, neutral conditions. The transition-metal-catalyzed OÀH insertion reaction meets this requirement. In 2006, Maier and Fu [6c] attempted an OÀH bond insertion reaction between a-diazo-a-phenylacetates and phenols by using chiral copper bisazaferrocene complexes as catalysts. However, the desired O À H insertion product (a-phenoxy-aphenylacetate) was obtained in 56 % yield with only 11 % ee. We [6d] and Uozumi and co-workers [6g] used chiral copper spiro bisoxazoline complexes and a chiral copper imidazoindolephosphine complex, respectively, for the same reaction and also obtained extremely l...

Enantioselective Palladium‐Catalyzed CH Functionalization of Indoles Using an Axially Chiral 2,2′‐Bipyridine Ligand

“…Initially,wefocused our attention on the establishment of the optimal reaction conditions for the CÀHfunctionalization of 2a using 1a.T oo ur gratification, by employing L1 as aligand, the reaction proceeded smoothly under the catalysis of [Pd(PhCN) 2 Cl 2 ]inCH 2 Cl 2 ,thus giving the desired product with 97 % ee ( Table 1, entries [1][2][3][4][5][6][7][8]. Theevaluation of ligands showed that the previously reported L2 also promoted the reaction, but because of its small dihedral angel upon chelation, 86 % ee was obtained (entry 9).…”

Further Developments and Applications of Oxazoline-Containing Ligands in Asymmetric Catalysis

“… 371 Zhou has applied the SpiroBOX ligands 1060 to asymmetric Cu-catalyzed α-diazo phosphonate carbenoid O–H insertions 372 and Pd-catalyzed carbenoid insertions into phenol O–H bonds. 373 …”

Synthesis of 2,2,2,‐Trichloroethyl Aryl‐ and Vinyldiazoacetates by Palladium‐Catalyzed Cross‐Coupling

“…The standard Wang conditions use both palladium and silver salts and both of these metal salts could potentially catalyze the decomposition of diazo compounds. [13] Scheme1.New synthetic route to TCE aryldiazoacetates.[b] Dr.E.A.V oight Research&Development, AbbVie 1N orth Waukegan Road, North Chicago, Illinois 60064( USA)[ + + ] These authors contributed equally to this work.Supporting information and the ORCID number(s) for the author(s) of this articlecan be foundu nder http://dx.…”

“…The standard Wang conditions use both palladium and silver salts and both of these metal salts could potentially catalyze the decomposition of diazo compounds. [13] Scheme1.New synthetic route to TCE aryldiazoacetates.…”

“…The standard Wang conditions use both palladium and silver salts and both of these metal salts could potentially catalyze the decomposition of diazo compounds. [13] Scheme1.New synthetic route to TCE aryldiazoacetates. The possibility that the variable yields were caused by product decomposition was investigated by means of ReactIR experiments ( Figure 1).…”