Synthesis and Applications of Bicyclo[1.1.0]butyl and Azabicyclo[1.1.0]butyl Organometallics

Abstract

Scheme 32. Anderson's study into the synthesis and reactivity of bridge lithiated bicyclo[1.1.0]butane. a) Bridge deprotonation and functionalization of bicyclo[1.1.0]butyl amide 128. b) Attempted enantioselective deprotonation of bicyclo[1.1.0]butane bridging methylenes. a The identity of the major stereoisomer was not determined. c) Sequential bridge deprotonation and functionalization. d) Application of deuterated bicyclo[1.1.0]butane 131 in the mechanistic study of difluorocarbene insertion.

Stereoselective Alder-Ene Reactions of Bicyclo[1.1.0]butanes: Facile Synthesis of Cyclopropyl- and Aryl-Substituted Cyclobutenes

“…The formation of 5r – 5v from symmetric arynes proceeded in excellent yields (89–99%), which were not compromised by ortho substituents ( 5w , 97%). Pleasingly, 3-methoxybenzyne delivered a single regioisomer 5x in 97% yield; in contrast, 4-methyl- and 4-chlorobenzyne afforded mixtures of regioisomers with respect to the aryne ( 5y and 5z ), albeit in high yields. Interestingly, the symmetric and unsymmetric naphthalynes generated from the corresponding regioisomeric silyl triflate precursors produced the same naphthyl cyclobutene 5aa in 95 and 97% yield, respectively.…”

“…In addition to such transformations, the ring expansion of BCBs to bicyclo­[n.1.1]­alkanes by formal one-, two-, or three-atom stepwise insertion processes has recently become a particularly valuable process due to the importance of these scaffolds in drug discovery . Finally, metalation of the acidic C–H bonds of BCBs provides further opportunities for scaffold diversification. , …”

Mechanistic Insight into Lewis Acid-Catalyzed Cycloaddition of Bicyclo[1.1.0]butanes with Ketene: Bicyclo[1.1.0]butanes Serving as an Electrophile

“…Because the bridgehead C–C bond in the BCB ring builds on the interactions of two unhybridized p orbitals, ,,− this bond is better viewed as a bent σ bond with π-bonding reactivity and might also interact with a Lewis acid. Possible intermediates of coordination of the TMS cation with the bridge BCB carbon were located (Figure S1), but they are all higher in energy than A and B .…”

Photoredox-Catalyzed Alkylarylation of N-Aryl Bicyclobutyl Amides with α-Carbonyl Alkyl Bromides: Access to 3-Spirocyclobutyl Oxindoles

“…b fac-Ir(ppy)3 (2 mol %) was used as photocatalyst instead of Na 2 -Eosin Y. h i b i t e d .The photocatalysis cycle started with single-electron transfer (SET) reduction of alkyl bromide 2a by the excited photoredox catalyst PC* to yield alkyl radical A, along with oxidized photocatalyst PC. Radical addition of the nucleophilic alkyl radical A to substrate 1a led to the intermediate B, which was intercepted by the aryl moiety of BCB via either anti-or syn-attack in an intramolecular fashion to afford a delocalized radical species C. Then, SET oxidation of C with PC occurred to deliver carbocation D and the starting photocatalyst.…”

“…Despite impressive progress in the central strained C–C bond difunctionalization reactions, these methods suffer from limited examples of electron-deficient BCBs and the requirement of the prefunctionalization of functional reagents. To extend applications of these strategies in organic synthesis, medicinal chemistry, and material science, the handling of highly strained metalated (aza)­bicyclo[1.1.0]­butanes to execute strain-release-driven difunctionalization of C–C σ-bonds with many radicals and nucleophiles has been established. , For example, Aggarwal and co-workers have developed a distinct class of BCB difunctionalization reactions by strain release in which the common intermediate BCB boronate complexes ( Int-A ) can be intercepted by electrophilic metal species, − radicals, or electrophiles , followed by a 1,2-boronate migration to yield cyclobutane products with a boronic ester (Scheme b).…”