Brook Rearrangement as Trigger for Carbene Generation: Synthesis of Stereodefined and Fully Substituted Cyclobutenes

Through a sequence that can be performed in a single vessel, involving regio- and diastereoselective copper-catalyzed carbomagnesiation of cyclopropenes, reaction with acylsilanes, and addition of THF as cosolvent, Brook rearrangement can be triggered to furnish a wide range of cyclobutenes with exceptional diastereoselectivity. Accordingly, stereodefined and highly substituted cyclobutenes with contiguous quaternary carbon centers can be synthesized easily and in high yield. The new strategy constitutes an unprecedented application of Brook rearrangement, one which involves the intermediacy of carbene species

Synthesis and Functionalization of Tertiary Propargylic Boronic Esters by Alkynyllithium-Mediated 1,2-Metalate Rearrangement of Borylated Cyclopropanes

Implementing the use of alkynyllithium reagents in a stereospecific 1,2-metalate rearrangement-mediated ring opening of polysubstituted cyclopropyl boronic esters provides a variety of tertiary pinacol boranes bearing adjacent tertiary or quaternary carbon stereocenters with high levels of diastereomeric purity. The potential of this strategy was demonstrated through a selection of α- and γ-functionalization of the propargyl boronic esters

Stereoselective Nucleophilic Halogenation at CF₃‑Substituted Nonclassical Carbocation

CF3-substituted cyclopropyl carbinol derivatives undergo regioselective and diastereoselective nucleophilic halogenation at the quaternary carbon center to provide acyclic products as a single diastereomer. The selectivity of the substitution is rationalized by the formation of a nonclassical cyclopropylcarbinyl cation intermediate, reacting at the most-substituted carbon center. Tertiary alkyl chlorides, bromides, and fluorides adjacent to a stereogenic C–CF3-motif are diastereomerically pure and can be obtained in few catalytic steps from commercially available alkynes

Carboxylate Assistance for Catalyzed Hydroarylations of Methylenecyclopropanes

Carboxylate assistance enabled efficient and chemoselective ruthenium(II)-catalyzed hydroarylations and hydroalkenylations of highly strained methylenecyclopropanes via C–H bond activation occurring with ring conservation of the cyclopropane moieties

Highly Diastereoselective Preparation of Aldol Products Using New Functionalized Allylic Aluminum Reagents

Chloro-substituted triethylsilyl enol ethers derived from cyclo­hexanone and related ketones are converted with aluminum powder in the presence of indium trichloride to functionalized allylic aluminum reagents which represent a new type of synthetic equivalent of metal enolates. These allylic organometallics undergo highly diastereo­selective additions to aldehydes and methyl aryl ketones, giving aldol products with a β-quaternary center

Zirconocene-Mediated Selective C–C Bond Cleavage of Strained Carbocycles: Scope and Mechanism

Several approaches using organozirconocene species for the remote cleavage of strained three-membered ring carbocycles are described. ω-Ene polysubstituted cyclopropanes, alkylidenecyclopropanes, ω-ene spiro[2.2]­pentanes, and ω-ene cyclopropyl methyl ethers were successfully transformed into stereodefined organometallic intermediates, allowing an easy access to highly stereoenriched acyclic scaffolds in good yields and, in most cases, excellent selectivities. DFT calculations and isotopic labeling experiments were performed to delineate the origin of the obtained chemo- and stereoselectivities, demonstrating the importance of microreversibility

Formation of Three New Bonds and Two Stereocenters in Acyclic Systems by Zinc-Mediated Enantioselective Alkynylation of Acylsilanes, Brook Rearrangement, and Ene-Allene Carbocyclization Reactions

Diastereoisomerically pure (<i>dr</i> > 99:1) and enantiomerically enriched (<i>er</i> up to 98:2) substituted propargyl diols possessing a tertiary hydroxyl group were synthesized in a single-pot operation from simple acylsilanes through a combined catalytic enantioselective alkynylation of acylsilanes, followed by an allenyl-Zn-Brook rearrangement and Zn-ene-allene (or Zn-yne-allene) cyclization reaction. Two remarkable features of these reactions are the near complete transfer of chirality in the allenyl-Zn-Brook rearrangement and the highly organized six-membered transition state of the Zn-ene-allene carbocyclization found by DFT calculations. In this process, <i>three new bonds and two new stereogenic centers are created in a single-pot operation in excellent diastereo- and enantiomeric ratios</i>. DFT calculations show that the allenyl-Zn-Brook rearrangement occurs in preference to the classic [1,2]-Zn-Brook rearrangement owing to its significantly lower activation barrier