Enantioselective Ruthenium-Catalyzed Benzocyclobutenone–Ketol Cycloaddition: Merging C–C Bond Activation and Transfer Hydrogenative Coupling for Type II Polyketide Construction

Abstract

The first enantioselective intermolecular metal-catalyzed cycloadditions of benzocyclobutenones via C-C bond oxidative addition are described. In the presence of a ruthenium(0) complex modified by ( R)-DM-SEGPHOS, tetralone-derived ketols and benzocyclobutenones combine to form cycloadducts with complete regio- and diastereoselectivity and high enantioselectivity. Using this method, the "bay region" substructure of the angucycline natural product arenimycin was prepared.

Site‐Selective C–C Cleavage of Benzocyclobutenones Enabled by a Blocking Strategy Using Nickel Catalysis

“…[8] In this development, a few examples of the reaction of BCBs with diphenylacetylene were also reported. Other representative intermolecular transformations of BCBs included the Pd-catalyzed intermolecular cross-metathesis reaction of BCBs with silacyclobutanes, [9] the Ru-catalyzed cycloaddition of BCBs with diols and ketols, [10] and the cross coupling of BCBs with indoles. [11] In most cases, the activation of C(sp 2 )ÀC(CO) (C1ÀC2) bond was observed, which was distinct from the reaction of cyclobutenones that usually cleaved the C(sp 3 )ÀC(CO) bond via a vinylketene intermediate.…”

“…[11] In most cases, the activation of C(sp 2 )ÀC(CO) (C1ÀC2) bond was observed, which was distinct from the reaction of cyclobutenones that usually cleaved the C(sp 3 )ÀC(CO) bond via a vinylketene intermediate. [3] Among the sporadic examples that involved the C1 À C8 bond cleavage of BCBs, [10][11][12] factors that controlled the site selectivity were not investigated. Undoubtedly, it is highly valuable to develop novel strategy to realize the functionalization of BCBs based on C1ÀC8 bond activation and to get more information about the reaction mechanism.…”

Controllable Skeleton Rearrangement of 3‐Substituted Cyclobutanones under Basic Conditions†

“…[ 2 ] Due to inherent high strain of four‐membered carbocycles, significant advances have been achieved in the field of carbon‐carbon single bond cleavage under the catalysis of transition‐metal or organocatalyst over the past decades. [ 3,4 ] However, enolate chemistry of cyclobutanone is less studied, arguably due to instability of the corresponding enol metal intermediate. [ 5 ]…”

Nickel‐Catalyzed Ring Expansion of Cyclobutanones towards Indanones

“…Catalytic ring opening reactions of small ring compounds provide an unique method to reshape more complex structural units and natural products [7–12] . In recent years, cyclobutanones have been used as important structural units in ring opening processes involving selective cleavage of C−C σ‐bonds, paving the way to the synthesis of various cyclic molecules with vigorous biological activity [13–16] …”