Catalytic Arylboration of Spirocyclic Cyclobutenes: Rapid Access to Highly Substituted Spiro[3.n]alkanes

Abstract

A method to achieve the synthesis of highly substituted spirocyclic cyclobutanes is disclosed. The reaction involves the catalytic arylboration of cyclobutenes. Depending on the substitution pattern of the cyclobutene, either a Cu/Pd- or a Ni-catalyzed reaction was utilized. In the case of the Cu/Pd-catalyzed reactions, the identification of a Cu-complex for arylboration was crucial to observe high selectivity. The synthetic utility of the products is demonstrated, and the mechanistic details are discussed.

Arylboration of Enecarbamates for the Synthesis of Borylated Saturated N‐Heterocycles

“…Our group has developed a Cu/Pd dual catalytic system for the arylboration of activated alkenes, including strained substrates such as spirocyclic cyclobutenes [30, 33] . Additionally, we and others, have previously reported Cu‐catalysed borylation of cyclobutenes [34] .…”

“…[32] Our group has developed a Cu/Pd dual catalytic system for the arylboration of activated alkenes, including strained substrates such as spirocyclic cyclobutenes. [30,33] Additionally, we and others, have previously reported Cu-catalysed borylation of cyclobutenes. [34] Based on this precedence, we hypothesized that borylcupration of N-Boc-2-azetine (1) might proceed selectively to deliver borylated azetidine product (2).…”

Recent progress in nickel-catalyzed carboboration of alkenes

“…In 2021, the Ni-catalyzed arylboration of spirocyclic cyclobutenes was reported by Brown and co-workers. 30 A variety of aryl bromides, for example that with electron-poor groups such as Cl ( 84 ) or ester ( 85 ), could undergo this reaction smoothly with good stereo- and chemical-selectivities. It is worth mentioning that non-activated alkenyl bromides ( 86 ) were also suitable for the reaction system led to moderate yields when used as the coupling reagents.…”

A stereochemical journey around spirocyclic glutamic acid analogs

“…In this work, we present the synthesis and preliminary evaluation of the library members as enzyme probes. It should be noted that while various spiro [3.3]heptanes attracted much attention in organic and medicinal chemistry in recent decades as six-membered ring isosteres, [28][29][30][31][32][33][34] 1,6-and especially 1,5-disubstituted derivatives remained heavily underrepresented (Fig. 4).…”