Synthesis of Highly Substituted Cyclopropanes via the Quasi-Favorskii Rearrangement of α,α-Dichlorocyclobutanols

We report a one-step, Ru(II)-catalyzed cyclopropanation reaction that is conceptually different from the previously reported protocols that include Corey-Chaykovsky, Simmons-Smith, and metal catalyzed carbene attack on olefins. Under the current protocol, various alcohols are transformed into sulfone substituted cyclopropanes with excellent isolated yields and diastereoselectivities. This new reaction forms highly congested cyclopropane products with three new C–C bonds, three or two new chiral centers and one new quaternary carbon center. 22 examples of isolated substrates are given. Previously reported synthetic routes for similar substrates are all multi-step, linear routes that proceed with overall low yields and poor control of stereochemistry. Experimental mechanistic investigations suggest initial metal-catalyzed dehydrogenation of the alcohol substrate and catalyst independent stepwise attack of two equivalents of sulfone on the aldehyde under basic conditions. While the Ru(II) is only responsible for the initial dehydrogenation step, the rate of aldehyde formation is crucial to maintaining the right balance of intermediates needed to afford the cyclopropane product.

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Enantioselective Multi-Component Cyclopropane Synthesis Enabled by Cu-Catalyzed Cyclopropene Carbometallation with Organoboron Reagent

10.26434/chemrxiv.7011548 ◽

2018 ◽

Author(s):

Zhanyu Li ◽

Mengru Zhang ◽

Yu Zhang ◽

Shuang Liu ◽

Jinbo Zhao ◽

...

Keyword(s):

Carbon Source ◽

Stereoselective Synthesis ◽

Organometallic Reagents ◽

Preliminary Results ◽

Quaternary Center ◽

Chiral Centers ◽

Substituted Cyclopropanes ◽

Proof Of Principle

Deployment of organoboron in lieu of the strongly basic organometallic reagents as carbon source in Cu-catalyzed cyclopropene carbometallation opens unprecedented three- component reactivity for stereoselective synthesis of poly-substituted cyclopropanes. A proof-of-principle demonstration of this novel carbometallation strategy is presented herein for a highly convergent access to poly-substituted aminocyclopropane framework via carboamination. Preliminary results on asymmetric desymmetrization with commercial bisphosphine ligands attained high levels of enantioselection, offering a straightforward access to enantioenriched aminocyclopropanes bearing all-three chiral centers, including an all-carbon quaternary center. This strategy may underpin a host of novel synthetic protocols for poly-substituted cyclopropanes.

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Interplay of the Ring and Steric Strains in the Highly Substituted Cyclopropanes

The Journal of Physical Chemistry A ◽

10.1021/acs.jpca.1c04777 ◽

2021 ◽

Author(s):

Sergey L. Khursan ◽

Ekaterina S. Akhmetshina

Keyword(s):

Substituted Cyclopropanes

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N-Chlorinative Ring Contraction of 1,4-Dimethoxyphthalazines via a Bicyclization/Ring-Opening Mechanism

Synthesis ◽

10.1055/s-0040-1706639 ◽

2020 ◽

Author(s):

Jeong Kyun Im ◽

Ilju Jeong ◽

Jun-Ho Choi ◽

Won-jin Chung ◽

ByeongDo Yang ◽

...

Keyword(s):

Ring Opening ◽

Reaction Conditions ◽

Ring Contraction ◽

Silyl Group ◽

Favorskii Rearrangement ◽

Mechanistic Analysis ◽

Group A ◽

Overall Efficiency ◽

Trichloroisocyanuric Acid

AbstractAn unprecedented N-chlorinative ring contraction of 1,2-diazines was discovered and investigated with an electrophilic chlorinating reagent, trichloroisocyanuric acid (TCICA). Through optimization and mechanistic analysis, the assisting role of n-Bu4NCl as an exogenous nucleophile was identified, and the optimized reaction conditions were applied to a range of 1,4-dimethoxyphthalazine derivatives. Also, an improvement of overall efficiency was demonstrated by the use of a labile O-silyl group. A bicyclization/ring-opening mechanism, inspired by the Favorskii rearrangement, was proposed and supported by the DFT calculations. Furthermore, the efforts on scope expansion as well as the evaluation of other electrophilic promoters revealed that the newly developed ring contraction reactivity is a unique characteristic of 1,4-dimethoxyphthalazine scaffold and TCICA.

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An Efficient Substrate-Induced Method for the Synthesis of CF3-Substituted Cyclopropanes by Metal-Free Reaction of Trifluoromethyl Styrylisoxazoles with Nitromethane

Synthesis ◽

10.1055/s-0040-1705976 ◽

2020 ◽

Author(s):

Feng Li ◽

Hai Ma ◽

Qing-he Zhao ◽

Guang-hao Yu ◽

Ye-chen Meng ◽

...

Keyword(s):

Functional Groups ◽

Phase Transfer ◽

Cyclization Reaction ◽

Metal Free ◽

Tert Butyl ◽

Pharmacological Interest ◽

Substituted Cyclopropanes

AbstractA series of (trifluoromethyl)cyclopropanes (TFCPs) tolerating a broad range of functional groups, known as tert-butyl bioisosteres, have been obtained from the cyclization reaction between nitromethane and 5-[β-(trifluoromethyl)styryl]isoxazoles in 70–94% yields and 75:25 to 90:10 dr. This method offers practical access to this cyclopropyl moiety of pharmacological interest, employing an inorganic base under phase-transfer conditions.

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