Hydrodealkenylative C(sp3)-C(sp2) bond fragmentation

Abstract

Chemical synthesis typically relies on reactions that generate complexity through elaboration of simple starting materials. Less common are deconstructive strategies toward complexity-particularly those involving carbon-carbon bond scission. Here, we introduce one such transformation: the hydrodealkenylative cleavage of C(sp³)-C(sp²) bonds, conducted below room temperature, using ozone, an iron salt, and a hydrogen atom donor. These reactions are performed in nonanhydrous solvents and open to the air; reach completion within 30 minutes; and deliver their products in high yields, even on decagram scales. We have used this broadly functionality tolerant transformation to produce desirable synthetic intermediates, many of which are optically active, from abundantly available terpenes and terpenoid-derived precursors. We have also applied it in the formal total syntheses of complex molecules.

Fig. 1.. Concept and applications of hydrodealkenylative fragmentation of C(sp³)–C(sp²) bonds.

(A) Deconstructive fragmentation of C–C bonds. (B) Overview and proposed mechanism of hydrodealkenylation. (C) Applications of hydrodealkenylation. X, activating functionality; R, alkyl group.

Fig. 2.. Applications of hydrodealkenylation in total synthesis.

Experiments performed on 1.0-mmol scale. Yields shown refer to isolated yields after SiO₂ chromatography. See the supplementary materials for experimental details. Ac₂O, acetic anhydride; Et₃N, triethylamine; DMAP, 4-dimethylaminopyridine; PCC, pyridinium chlorochromate; BF₃.OEt₂, boron trifluoride diethyl etherate; EtOH, ethanol; TBS, tert-butyldimethylsilyl.

Fig. 3.. Observations consistent with the intermediacy of a carbon radical.

Experiments performed on ≥0.5-mmol scale. Yields shown refer to isolated yields after SiO₂ chromatography. See the supplementary materials for experimental details. d.r., diastere-omeric ratio; Ph₂S₂, diphenyl disulfide; ORTEP, Oak Ridge thermal ellipsoid plot.