Pd-Catalyzed umpolung asymmetric allylic alkylation of hydrazones to vicinal tertiary and quaternary chiral carbon centers

Abstract

Diastereo- and enantioselective construction of vicinal tertiary and quaternary carbon centers is a great challenge in synthetic chemistry. Herein, we report a facile and efficient protocol to construct vicinal tertiary...

Palladium-catalyzed allylic alkylation of hydrazones with hydroxy-tethered allyl carbonates: synthesis of functionalized hydrazones

“…Based on previous works 13 and the control experiments (detailed in the ESI†), a plausible mechanism was proposed as shown in Scheme 3. Under palladium catalysis, π-allylpalladium zwitterionic intermediate A was produced through decarboxylation/deprotonation by the release of CO 2 and t -BuOH.…”

“…There were two possible paths to afford intermediate D . Path A 12,13,18 involves an inner-sphere mechanism through the attack of the nitrogen anion of hydrazone B-1 to the π-allyl-Pd complex followed by [3,3]-reductive elimination. Path B 10,19 involves an umpolung reaction mechanism featuring a direct attack of the carbon anion of hydrazone B-2 to the terminal carbon of the π-allyl-Pd complex.…”

“…Most recently, Hou and Ding described the allylic alkylation of simple hydrazones by a palladium-mediated [3,3]-reductive elimination process. 13 The hydrazone functional group was not maintained in this reaction due to substrate constraints. Notably, the palladium-catalyzed allylation reactions described above required an external base for the activation of the hydrazone.…”

The Catalytic Asymmetric Allylic Alkylation of Acyclic Enolates for the Construction of Quaternary and Tetrasubstituted Stereogenic Centres

“…The following year, Hou developed a synthesis of azo compounds 192 with high levels of enantioselectivity by means of a palladium-catalysed AAA reaction of hydrazones 190 with substituted electrophile 191, LiHMDS as the base and (S,S)-L23 as the NHC ligand for palladium (Scheme 38). [63] The enantioselectivity of the reaction was found to be excellent for a variety of aryl substituents on 190, giving 192 a-c with complete diastereoselectivity and 91-94 % ee. The yields ranged from moderate to good as a result of competing N-alkylation, as well as C-alkylation at the less substituted position of the electrophile, giving rise to unwanted side-products.…”

COAP/Pd-Catalyzed Linear Asymmetric Allylic Alkylation for Optically Active 3,3-Disubstituted Oxindole Derivatives with a Four-Carbon Amino Side Chain

“…For classical asymmetric allylic alkylation (AAA), an allylic electrophile bearing an appropriate leaving group (LG) was utilized to react with a nucleophile (NuH) in the presence of a chiral Pd-complex as the catalyst. During the process, the consumption of a stoichiometric amount of the base leads to a stoichiometric amount of the conjugate acid . Meanwhile, the AAA reaction also generates equivalent byproducts derived from the leaving group by along with the desired Nu–C bond formation .…”