Sonogashira‐type cross‐couplings are one of the most significant alkynylations in organic chemistry. One of the first palladium‐catalyzed intramolecular Heck/Sonogashira reactions of alkenes with terminal alkynes is now reported. With this method, a variety of uniquely substituted chiral benzene‐fused heterocycles bearing a propargyl‐substituted all‐carbon quaternary stereocenter were obtained in a straightforward, high‐yielding, and highly stereoselective manner under mild conditions. Salient features of this process include the use of readily available substrates, high selectivities, a broad substrate scope as well as versatile product functionalizations.
The first example of highly enantioselective intramolecular hydroarylation of allyl aryl ethers was realized by palladium-catalyzed reductive heck reactions utilizing a new chiral sulfinamide phosphine ligand (N-Me-XuPhos). N-Me-XuPhos can be easily prepared on gram scale from readily available starting materials in a one-pot synthesis approach. A series of optically active 2,3-dihydrobenzofurans bearing a quaternary stereocenter were obtained in good yields and with excellent enantioselectivities. The practicality of this reaction was validated in the straightforward synthesis of CB2 receptor agonists. Moreover, deuterium was efficiently incorporated into the products.
A highly
enantioselective palladium-catalyzed iodine atom transfer
cycloisomerization of unactivated alkenes has been developed. This
represents the first example of highly enantioselective carboiodination
of olefin-tethered aryl iodides, which provides a perfect atom economy
method to construct a series of optically active 2,3-dihydrobenzofuran,
indolines and chromane bearing an alkyl iodide group in moderate to
good yields. Moreover, the use of readily available starting materials,
a broad substrate scope, high selectivity, mild reaction conditions,
as well as versatile transformation of the product make this approach
attractive. The mechanism of this Pd(0)-catalyzed asymmetric carboiodination
of alkenes has been investigated with density functional theory.
A highly enantioselective dicarbofunctionalization of unactivated alkenes was implemented by a Pd‐catalyzed asymmetric tandem Heck/Suzuki coupling reaction. This reaction represents the first example of a highly enantioselective intramolecular cyclization/cross‐coupling of olefin‐tethered aryl halides with alkyl‐, alkenyl‐ or arylboronic acids, and provides rapid access to a number of chiral compounds, such as dihydrobenzofurans, indolines, chromanes, and indanes bearing a quaternary stereocenter, in good yields with excellent enantioselectivities. The practicality of this reaction was validated in the modification of biologically complex molecules such as peptides, piperitol, CB2 receptor agonists, etc. Moreover, the synthesis of two enantiomers can be easily realized by simple change in the order of the steps in the coupling sequence.
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