Palladium‐Catalyzed Enantioselective Reductive Heck Reactions: Convenient Access to 3,3‐Disubstituted 2,3‐Dihydrobenzofuran

Abstract

The first example of highly enantioselective intramolecular hydroarylation of allyl aryl ethers was realized by palladium-catalyzed reductive heck reactions utilizing an ew chiral sulfinamide phosphine ligand (N-Me-XuPhos). N-Me-XuPhos can be easily prepared on gram scale from readily available starting materials in aone-pot synthesis approach.A series of optically active 2,3-dihydrobenzofurans bearing aq uaternary stereocenter were obtained in good yields and with excellent enantioselectivities.T he practicality of this reaction was validated in the straightforwards ynthesis of CB2 receptor agonists.M oreover,d euterium was efficiently incorporated into the products.

Nickel-Catalyzed Asymmetric Reductive Arylbenzylation of Unactivated Alkenes

“…After quenching with water, the hyroarylation product 3g-1 was yielded in as imilar enantiomeric excess as 3g in Table 1, implying that the nickelmediated migratory insertion is the enantiodetermining step. [14] It is well-known that alkyl halides can form radicals with nickel catalysts. [15,16] Thus we conducted the reaction using an alkyl bromide with at erminal olefinic unit (Scheme 4A).…”

Nickel-Catalyzed Enantioselective C(sp 3 )–H Arylation of Ketones with Aryl Ethers via Selective C Ar –O Cleavage to Construct All-Carbon Quaternary Stereocenters

“…In 1992, Overman and co-workers developed a seminal work on palladium-catalyzed intramolecular asymmetric Heck reaction for the synthesis of chiral spiro-oxindoles with quaternary stereocenters. 15 Subsequently, transition metalcatalyzed asymmetric Heck reaction, [16][17][18] conjugate addition, 19,20 coupling of tertiary carbon radicals 21 and αarylation of carbonyl and nitrile derivatives [22][23][24][25][26][27][28][29][30][31][32] have been well developed for the synthesis of aryl-substituted quaternary stereocenters (Scheme 1a). However, nickel-catalyzed enantioselective α -arylation of carbonyl compounds for the construction of quaternary carbon centers was only reported in limited examples (Scheme 1b).…”

Palladium-Catalyzed Asymmetric Domino Heck/Carbocyclization/Suzuki Reaction: A Dearomatization of Nonactivated Naphthalenes

“…Alternatively, by switching the cross-coupling of alkyl-PdX to reductive elimination, intriguing reductive Heck and Heck carboiodination reactions have been reported (Scheme 1A). [39][40][41][42][43][44] Recently, a dearomative rearrangement of biaryl phosphine ligated Pd(II) complexes which was involved in a Pd(II)-mediated insertion of an aryl group into an based spirocycles have emerged (Scheme 1B). 46,47 Based on our recent interest in the field, 35,48 we hypothesized that the β-naphthyl group might be activated by the key alkyl-Pd species in domino Heck reaction through an intramolecular coordination interaction (Scheme 1C).…”