Stereoselective 1,2-Dicarbofunctionalization of Trisubstituted Alkenes by Palladium-Catalyzed Heck/Suzuki or Heck/Sonogashira Domino Sequence

Abstract

Highly enantioselective and diastereoselective 1,2diarylation and 1,2-arylalkynylation of trisubstituted alkenes are reported via the palladium-catalyzed Heck/Suzuki or Heck/Sonogashira domino sequence. These alkenes represent an extension of enantioselective dicarbofunctionalization from terminal alkenes to trisubstituted ones based on anionic capture of the secondary alkyl-Pd intermediate. A wide range of 3,3′-spirooxindoles, featuring vicinal spiro quaternary and tertiary stereocenters, is efficiently constructed in one step with up to 94% enantioselectivities and excellent diastereoselectivities (>19:1 dr). The practicability of this method is shown by its broad substrate scope and versatile transformations of the resulting products.

Enantioselective Reductive Divinylation of Unactivated Alkenes by Nickel-Catalyzed Cyclization Coupling Reaction

“…The majority of reports have focused on the reactions of aryl-tethered alkenes, in which the rigid aromatic ring is incorporated to improve the selectivity (Scheme a). Over the past few years, studies along these lines have progressed significantly, with the scope expanded from single-molecule to two-component reactions, from activated substrates , to unactivated alkenes, , and from nucleophile–electrophile reactions , to cross-electrophile couplings. , In short contrast, the reactions of nonaromatic substrates remain elusive, and the major advances have been limited to carbamoyl-tethered alkenes for producing chiral pyrrolidinone (Scheme b) . The development of new tethered alkenes for asymmetric dicarbofunctionalizations is essential for improving the structural diversity of chiral cyclic compounds.…”

Nickel-Catalyzed Reductive Asymmetric Aryl-Acylation and Aryl-Carbamoylation of Unactivated Alkenes

“…In contrast, the reactions employing the PyBOX L9 or PHOX L10 as a ligand failed to deliver compound 3aa (entries 9 and 10). Next, several Ni(II) salts and Ni(COD) 2 were surveyed (entries [11][12][13][14], and the highest enantioselectivity was achieved in the case of NiBr 2 •diglyme (entry 14). In this case, the yield was also increased to 38%.…”

“…Supporting Information is available and includes Experimental procedures, characterization data, and 1 H NMR, 13 C NMR, 19 F NMR and HPLC chromatograms for products (PDF).. .…”

“…[1][2][3][4][5][6] The majority of these reactions relies on a facially selective Heck-type arylmetallation of the pendant olefinic unit as the enantiodetermining step, 7 which is followed by trapping of the generated σ-alkylmetal species with either a nucleophile or an electrophile. Based on this strategy, asymmetric aryl-alkylation, [8][9][10] diarylation, [10][11][12][13] arylbenzylation, 14 aryl-alkenylation 15,16 and aryl-alkynylation 13,17,18 of incorporated alkenes have been developed under palladium, copper or nickel catalysis.…”

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

“…Heck-Sonogashira reaction, [30][31][32] Heck-Suzuki reaction, 33,34 and Heck carbonylative reaction, [35][36][37][38] have been developed for the synthesis of valuable structures (Scheme 1a). Alternatively, by switching the crosscoupling of alkyl-PdX to reductive elimination, intriguing reductive Heck and Heck carboiodination reactions have been reported (Scheme 1a).…”