Enantioselective Dicarbofunctionalization of Unactivated Alkenes by Palladium‐Catalyzed Tandem Heck/Suzuki Coupling Reaction

Abstract

Ah ighly enantioselective dicarbofunctionalization of unactivated alkenes was implemented by aP d-catalyzed asymmetric tandem Heck/Suzuki coupling reaction. This reaction represents the first example of ah ighly enantioselective intramolecular cyclization/cross-coupling of olefin-tethered aryl halides with alkyl-, alkenyl-or arylboronic acids,and provides rapid access to an umber of chiral compounds,s uch as dihydrobenzofurans,i ndolines,c hromanes,a nd indanes bearing aquaternary stereocenter,ingood yields with excellent enantioselectivities.T he practicality of this reaction was validated in the modification of biologically complex molecules such as peptides,p iperitol, CB2 receptor agonists,e tc. Moreover,t he synthesis of two enantiomers can be easily realized by simple change in the order of the steps in the coupling sequence.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Palladium‐Catalyzed C—C Bond Activation/Suzuki Reaction of Methylenecyclobutanes

“…Unfortunately, using enantiopure L3 only gave the product in low ee (39% ee). Further screening of bases proved K 2 CO 3 was the base of choice and raised the yield to 83% (entries [11][12][13][14]. Other common solvents such as toluene and THF resulted in lower yields (entries 15-18).…”

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).…”

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

“…By using the carbonylation reaction to interrupt the Heck process, Correia's group, 37 Zhu's group, 38 and Guan's group 39 were able to independently construct 3,3′-disubstituted dihydrobenzofurans, 2-oxindole-based spiro-lactones/lactams, and 3,3′-disubstituted oxindoles in excellent enantioselectivities. Moreover, asymmetric palladium-catalyzed Heck/ Suzuki and Heck/Sonogashira domino sequences were developed by Zhang's group [40][41][42][43] and Lu's group, 44 respectively. Alternatively, based on nickel-or copper-based chiral catalysts, Cong and Fu 45 and You and Brown 46 demonstrated the enantioselective dicarbofunctionalization of olefins through the reactions of aryl-9-Borabicyclo [3.3.1]nonane or aryl-Bpin-tethered alkenes with electrophilic alkyl-or aryl-halides (Figure 1b).…”

“…(a) Zhu's group [32][33][34] , Correia's group, 37 Zhu's group, 38 Guan's group, 39 Zhang's group, [40][41][42][43] and Lu's group 44 (c) Kong's group, 47,48 Jin and Wang, 49…”