Trifluorodiazoethane (CF₃CHN₂) in the Uncatalyzed Cyclopropanation of 3‐Arylmethylenebenzofuran‐2(3 H)‐ones

Abstract

The uncatalyzed cyclopropanation of 2,2,2-trifluorodiazoethane onto 3-arylmethylenebenzofuran-2(3 H)ones leads to highly functionalized trifluoromethylated spirocyclopropanes. At hermal activation mode not requiring the additiono fatransition metal provided high product yields, whereas as alt effect benefited the diastereomeric ratios obtained. The products are readily elaborated to non-spiro derivatives.2,2,2-Trifluorodiazoethane( CF 3 CHN 2 )h as emerged as av ery attractive CF 3 -containing synthon for the construction of fluorinated molecules featuring aC F 3 structural subunit. This gaseous and explosive reagent is conveniently generated in situ by conversion of trifluoroethylamine hydrochloride in the presence of sodium nitrite. Alternatively,g aseous CF 3 CHN 2 can be draggedo ff by argon flow into ad ifferent reaction vessel or stock solutionso fC F 3 CHN 2 can be prepared. Recently,C F 3 CHN 2 has demonstrated aw ider ange of applicationsi nvarious reactions such as 1,3-dipolar cycloaddition, [1] cyclopropenation, [2] cyclopropanation, [3] aziridination, [4] trifluoroethylation of terminal alkynes, [5] reactionw ith organoborons, [3d, 6] and otherr eactions. [7] Cyclopropanation by means of CF 3 CHN 2 has attracted much attentionn ot only because cyclopropanei saw idespread motif in natural and synthetic compounds, but also because fluorine strongly influences electronic and steric properties as well as physiological properties, bioactivity,a nd metabolic stabilityo f fluorinated molecules. [8] Early studies focused on photolysis of CF 3 CHN 2 to generate the trifluoromethylcarbene, [9] whereas more recent cyclopropanation reactions were catalyzed by transition metals, for example, Fe, [3a,e,i] Co, [3h] Cu, [3b,c,f,k] Ru, [3a] Rh, [3c,g] or Pd. [3d] Metal-free conditions for cyclopropanation by means of CF 3 CHN 2 are less studied. In 2013, Mykhailiuk and co-

Recent Progress Toward the Synthesis of Trifluoromethyl‐ and Difluoromethyl‐Substituted Cyclopropanes

“…Later in 2016, the same research group extended the scope of the reaction to 3‐arylmethylenebenzofuran‐2(3 H )‐ones 41 a – j and 43 a – d (Scheme ) . Under similar reaction conditions, the cyclopropanation reaction with electron‐withdrawing and electron‐donating substituted ( E )‐ and ( Z )‐3‐arylmethylenefuranones was achieved in moderate to excellent yields with excellent regio‐ and diastereoselectivities favoring the trans isomer.…”

Additive‐Free Synthesis of Trifluoromethylated Spiro Cyclopropanes and Their Transformation into Trifluoromethylated Building Blocks

“…[9] The groups of Cahard, Xiao and Ma developed convenient routes to access spiro-TFCps through the sequential [3 + 2] cycloaddition/ring contraction reaction of 3- arylmethylenebenzofuran-2(3H)-ones, 3-ylideneoxindoles and azlactones with CF 3 CHN 2 (Scheme 1e). [10] Inspired by these advances in the synthesis of trifluoromethylated cyclopropanes using trifluorodiazoethane, we envisioned that highly activated alkenes such as arylideneindanediones would readily participate in this reaction to provide an important class of trifluoromethylcyclopropanes possessing the properties of donor-acceptor cyclopropanes (DACs). It is worthwhile to mention that DACs have emerged as indelible substrates to assemble densely functionalized scaffolds.…”

Silver-Catalyzed Direct Synthesis of Trifluoromethylated Enaminopyridines and Isoquinolinones Employing Trifluorodiazoethane

“…3 Seminal studies by Carreira, Mykhailiuk, Cahard, Ma, and others have established the indispensable role of trifluorodiazoethane as a versatile reagent in the construction of challenging scaffolds under viable conditions. 4,5 This gaseous reagent has been extensively used as a 1,3-dipole for the construction of trifluoromethylated heterocycles. 6 In addition, numerous methods employing this reagent as a trifluoromethylated carbene for cyclopropanation and insertion reactions have emerged.…”