Efficient Synthesis of Orphaned Cyclopropanes Using Sulfones as Carbene Equivalents

Abstract

Small molecules containing 1,1-dimethylcyclopropanes are prevalent throughout nature but are difficult to synthesize using state-of-the-art metal-catalyzed carbene transfer methods without competing 1,2-hydride shifts. Herein, we introduce a mechanistically distinct platform to transfer 1,1-dialkylcarbene units to olefins using carbometalation reactions of dialkyl sulfonyl anions. In the presence of NaNH 2 or n-BuLi in ethereal solvents, dialkyl sulfones react with styrenes and arylbutadienes between 23 and 70 °C to produce the corresponding 1,1-dialkylcyclopropanes. We report 40 examples of this reactivity including 16 different styrenes (up to 89% isolated yield), 9 arylbutadienes (51−88% yield), and 13 different sulfones (46−80% yield). In addition, we report an example of a sequential cyclopropanation reaction using this method. Preliminary mechanistic studies suggest a stepwise anionic process that is initiated by the direct addition of sulfonyl anions to a carbon−carbon double bond.

Catalytic Asymmetric Deoxygenative Cyclopropanation Reactions by a Chiral Salen-Mo Catalyst

“…The chiral cyclopropane motif is widely distributed in an array of natural products and approved drugs (Figure A). − The unique properties of cyclopropanes make them appealing candidates in drug discovery, especially in their optically pure form . These aspects have stimulated great interest from the chemical community in terms of the asymmetric synthesis of cyclopropanes. − Among the many methods used to achieve this goal, the transition-metal-catalyzed asymmetric cyclopropanation reaction of alkenes with chiral metal carbene intermediates, derived from diazo compounds and chiral metal complexes, was found to be one of the most straightforward, powerful, and useful methods (Figure B). − Unfortunately, the handling of diazo compounds requires special care due to their potentially explosive nature and the necessary use of hazardous reagents for their preparation. , Therefore, significant efforts have been devoted to the development of operationally safe and readily available surrogates for diazo compounds as carbene precursors. , …”

Catalytic Asymmetric Cyclopropanations with Nonstabilized Carbenes

“…Here we show that this approach provides a general entry into catalytic asymmetric cyclopropanations. Notably, the cobalt-catalyzed cyclopropanation allows for the transfer of alkyl-substituted carbenes, a process that is not efficient under Simmons–Smith conditions, even in a non-asymmetric context.…”

“…14 Here we show that this approach provides a general entry into catalytic asymmetric cyclopropanations. Notably, the cobalt-catalyzed cyclopropanation allows for the transfer of alkyl-substituted carbenes, 15 a process that is not efficient under Simmons−Smith conditions, even in a nonasymmetric context. The dimethylcyclopropanation of model 1,3-diene 1 can be carried out in 95% yield using 2,2-dichloropropane, Zn, and (PDI)CoBr 2 catalyst 3 (PDI = pyridine diimine) (Figure 2).…”

Visible-light-induced oxidant/additive-free atom-economic synthesis of multifunctionalized cyclopropanes via energy transfer

“…1). 3 Researchers continue to look for more complex cyclopropane-containing saturated frameworks to find promising lead structures. However, cyclopropane has traditionally been synthesized using methylating reagents such as diazomethane, 4 the Simmons–Smith protocol, 5 and sulfur ylide chemistry, 6 among others, 7 which are inherently unsafe and involve difficulties in removing the transition-metal residues.…”