The asymmetric allylic alkylation (AAA), which features employing active allylic substrates, has historical significance in organic synthesis. The allylic C−H alkylation is principally more atom-and step-economic than the classical allylic functionalizations and thus can be considered a transformative variant. However, asymmetric allylic C−H alkylation reactions are still scarce and yet underdeveloped. Herein, we have found that Z/E-and regioselectivities in the Pd-catalyzed asymmetric allylic C−H alkylation of 1,4-dienes are highly dependent on the type of nucleophiles. A highly stereoselective allylic C−H alkylation of 1,4-dienes with azlactones has been established by palladium-chiral phosphoramidite catalysis. The protocol proceeds under mild conditions and can accommodate a wide scope of substrates, delivering structurally divergent α,αdisubstituted α-amino acid surrogates in high yields and excellent levels of diastereo-, Z/E-, regio-, and enantioselectivities. Notably, this method provides key chiral intermediates for an efficient synthesis of lepadiformine marine alkaloids. Experimental and computational studies on the reaction mechanism suggest a novel concerted proton and two-electron transfer process for the allylic C−H cleavage and reveal that the Z/E-and regioselectivities are governed by the geometry and coordination pattern of nucleophiles.
In
the presence of tetrabutylammonium decatungstate and chiral
spiro phosphoric acid, a light-mediated asymmetric C–H functionalization
of unactivated hydrocarbons with exocyclic enones has been established.
A wide range of cycloalkanes, benzylic, and allylic hydrocarbons are
tolerated. This protocol proceeds via a hydrogen atom transfer/radical
addition/hydrogen abstraction/enantioselective protonation relay process.
Asymmetric
functionalization of inert C(sp3)–H
bonds is a straightforward approach to realize versatile bond-forming
events, allowing the precise assembly of molecular complexity with
minimal functional manipulations. Here, we describe an asymmetric
photocatalytic C(sp3)–H bond addition to α-substituted
acrylates by using tetrabutylammonium decatungstate (TBADT) as a hydrogen
atom transfer (HAT) photocatalyst and chiral phosphoric acid as a
chiral proton-transfer shuttle. This protocol is supposed to occur
via a radical/ionic relay process, including a TBADT-mediated HAT
to cleave the inert C(sp3)–H bond, a 1,4-radical
addition, a back hydrogen abstraction, and an enantioselective protonation.
A variety of inert C–H bond patterns and α-substituted
acrylates are well tolerated to enable the rapid synthesis of enantioenriched
α-stereogenic esters from simple raw materials.
A palladium-catalyzed asymmetric α-allylation of aldehydes with alkynes has been established by integrating the catalysis of enamine and chiral hydridopalladium complex that is reversibly formed from the oxidative addition of Pd(0) to chiral phosphoric acid. The ternary catalyst system, consisting of an achiral palladium complex, a primary amine, and a chiral phosphoric acid allows the reaction to tolerate a wide scope of α,α-disubstituted aldehydes and alkynes, affording the corresponding allylation products in high yields and with excellent levels of enantioselectivity.
The
rapid assembly of an easily accessible terminal alkene, an
aliphatic C(sp3)–H coupling partner, and allyl carbonate
has been established by merging hydrogen atom transfer photocatalyst-mediated
nucleophile generation and palladium-catalyzed allylic alkylation.
The synthetic utility of this strategy is embodied by a concise synthesis
of (±)-mesembrine. Mechanistic studies suggest that this protocol
proceeds via a radical/ionic relay process, and a carbanionic species
serves as a key intermediate for nucleophile attack on π-allylpalladium
through a classic two-electron allylation pathway. This protocol showcases
an atom-economic and environmentally friendly method to generate a
nonstabilized nucleophile for transition-metal catalysis.
Asymmetric allylic C-H alkylation of 1,4-pentadienes with α-angelica lactones has been developed by tri-axial phosphoramidite-palladium catalysis. This reaction can tolerate a range of functional groups under mild conditions, furnishing versatile...
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