Synthesis of Spirocyclic γ-Lactones by Cascade Beckwith–Dowd Ring Expansion/Cyclization

Abstract

A range of spirocyclic γ-lactones have been prepared exploiting a Beckwith-Dowd ring expansion cascade involving 1-, 3-, 4-, and 5-carbon expansion of cyclopentanone and cyclohexanone followed by 5-exo-trig or 5-exo-dig cyclization. This radical cascade reaction can be achieved with various substrates to provide a broad range of γ-lactones spirofused to 6- to 10-membered cycloalkanones.

Thirty Years of (TMS)3SiH: A Milestone in Radical-Based Synthetic Chemistry

“…Slow addition of TTMSS onto 353 led to the spirolactone 354 as the only product. 257 Using similar conditions, better hydrogen atom donor Bu 3 SnH provided 354, along with the Beckwith-Dowd ring expansion product. Lactones spirofused to larger cycloalkanones such as 356 were also accessible from ketoester 355, using this strategy.…”

One-Pot Synthesis of Spirocyclic or Fused Pyrazoles from Cyclic Ketones: Calcium Carbide as the Carbon Source in Ring Expansion

“…Another well-known and efficient method is the Dowd–Beckwith ring expansion reaction, in which the 2-oxocyclohexanecarboxylate compounds are transformed to medium-sized ring cyclic ketones. However, this process requires the addition of toxic or explosive reagents such as AIBN and Bu 3 SnH, and environmentally unfriendly haloalkane substrates are used as the carbon source (Scheme b) …”

Visible-light-driven palladium-catalyzed Dowd–Beckwith ring expansion/C–C bond formation cascade

“…7 Although many progress have been made in the reaction system, the ring expansion/H-atom abstraction is still the mainstream transformation, which limited its application in the radical cascade. 8 Recently, the light-induced transition-metal catalysis has emerged as a versatile platform to realize transformations that are otherwise difficult to achieve. In this field, the groups of Gevorgyan, Fu, Yu and others recently demonstrated a series of fantastic chemical transformations through visible light-induced Pd-catalyzed alkyl couplings, wherein the hybrid alkyl Pd( i )-radical species enabled the alkyl couplings achievable.…”