Palladium‐Titanium Relay Catalysis Enables Switch from Alkoxide‐π‐Allyl to Dienolate Reactivity for Spiro‐Heterocycle Synthesis

Abstract

Reported herein is the divergent syntheses of [5,5] and [6,5] spiro-heterocycles under Lewis-acid-assisted palladium catalysis. In particular, an unprecedented switch from alkoxide-π-allyl to dienolate reactivity was achieved by the use of palladium-titanium relay catalysis, and represents umpolung reactivity of vinylethylene carbonates. This method uses a simple procedure and commercially available catalysts, and delivers both classes of spiro-heterocycles, bearing three contiguous stereocenters, in high yield and uniformly excellent diastereoselectivity.

An Update of Transition Metal-Catalyzed Decarboxylative Transformations of Cyclic Carbonates and Carbamates

“…Umpolung reactivity of the π-allyl zwitterionic species was first noted by Guo and co-workers [39] and later, it was further explored by the Zhao group [40]. In the presence of a palladium and titanium catalyst, the umpolung annulation process occurred with the use of aurones and VCC as Umpolung reactivity of the π-allyl zwitterionic species was first noted by Guo and co-workers [39] and later, it was further explored by the Zhao group [40]. In the presence of a palladium and titanium catalyst, the umpolung annulation process occurred with the use of aurones and VCC as starting materials toward the formation of [6,5] and [5,5] spiro-heterocycles bearing three contiguous stereocenters (Scheme 8).…”

“…For example, the Xiao group realized an enantioselective [5 + 2] cycloaddition reaction of VCCs and α-diazoketones by merging photoactivation and Pd catalysis and a variety of seven-membered lactones bearing chiral quaternary stereocenters with high enantioselectivity were delivered through this methodology [35]. Umpolung reactivity of the π-allyl zwitterionic species was first noted by Guo and co-workers [39] and later, it was further explored by the Zhao group [40]. In the presence of a palladium and titanium catalyst, the umpolung annulation process occurred with the use of aurones and VCC as Umpolung reactivity of the π-allyl zwitterionic species was first noted by Guo and co-workers [39] and later, it was further explored by the Zhao group [40].…”

Extended Enolates: Versatile Intermediates for Asymmetric C‐H Functionalization via Noncovalent Catalysis

“…Based on this umpolung strategy, vinylethylene carbonates 173 reacted with aurones 176 as special class of α,β-unsaturated cyclic ketones to yield spiro-heterocycles, such as 177, with three contiguous stereocenters in high diastereoselectivity, but moderate enantioselectivity. [107] Alkynylogous enolates, the alkynyl analogs of metal dienolates, which might present the alkynyl and allenyl tautomeric forms 178 and 179, could be generated in situ from the corresponding alkynyl or allenyl esters. The reactivity of transiently formed alkynylogous enolates have been explored to a limited extent.…”

“…Just in the opposite direction, Zhao group reported the switch from alkoxide‐π‐allyl to metal dienolate reactivity by using Pd−Ti relay catalysis. Based on this umpolung strategy, vinylethylene carbonates 173 reacted with aurones 176 as special class of α,β‐unsaturated cyclic ketones to yield spiro‐heterocycles, such as 177 , with three contiguous stereocenters in high diastereoselectivity, but moderate enantioselectivity [107] …”

Recent Advances in the Cycloaddition Reactions of 2‐Benzylidene‐1‐benzofuran‐3‐ones, and Their Sulfur, Nitrogen and Methylene Analogues

“…The same year, Zhao's group used 2benzylidene-1-benzofuran-3-ones 22 and vinylethylene carbonates (VECs) 37 to obtain benzofuran [5,5] spirocycles 38. [24] The VECs 37 could be catalyzed by PdL n to form an intermediate similar to a 1,n-dipole (Scheme 5c). [25] N-Heterocyclic carbenes (NHC) are a unique kind of catalyst.…”