Cyclopropanes with trifluoroacetic acid

Styrene is reported to undergo reduction upon treatment with trifluoroacetic acid and triethylsilane,203 although competing polymerization reactions limit the yield of ethylbenzene to only 30% (Eq. 63).70 Vinylcyclopropane is reduced to ethylcy-clopropane within 30 minutes under similar conditions (Eq. 64) 232 It is important to note that the cyclopropane ring of ethylcyclopropane can be opened under these reaction conditions, albeit with longer reaction times, to give some trans-2-pentene in the final reaction mixture.233... 

Treatment of bis-spirocyclopropanated isoxazolidines 551 with trifluoroacetic acid in acetonitrile furnishes 3-spiro-cyclopropanated azetidin-2-ones 552 in excellent yields (Equation 226) <2004EJ04158>. 

Ring enlargement of chromone to benzoxepins has been reported (see also Section 7.07.5). The in situ generation of benzopyrylium triflate 335 by reaction of 334 with Me3SiOTf followed by addition of ethyldiazoacetate and catalytic copper(ll) triflate yielded cyclopropane 336 as a single diastereomer. Treatment of compound 336 with trifluoroacetic acid resulted in the formation of 2,3-benzoxepin 337 (Scheme 47). 

Intramolecular ring-opening of electrophilic cyclopropanes has been used in the synthesis of indolochinolizine compounds (625) by treatment of the indole 624 with trifluoroacetic acid/trifluoroacetic anhydride (equation 220) . A limited number of... 

The participation of an urea group in the acid-catalyzed cleavage of a cyclopropane bond, which is one of the key steps in the synthesis of aza- and oxa-eburnamonine, has been reported.(2-Cyclopropylphenyl)benzylsulfone (13) was observed to give l-(2-benzylsulfonyl-phenyl)propyl trifluoroacetate (14) when treated with trifluoroacetic acid. ° ... 

Bis(alkylsulfanyl)cyclopropanes (cyclopropanone dithioacetals) are transformed to a-hydroxy-acetones in hot aqueous formic acid and to acetones in aqueous trifluoroacetic acid at ambient temperature, the latter reaction probably via reduction of an intermediate ot-methyl thioketone by methylsulfide. For example, 7 gave 8 with hot aqueous formic acid and 9 with trifluoroacetic acid. ... 

The reaction of sulfur dioxide with cyclopropanes in trifluoroacetic acid at 20 °C affords mixtures of isomeric 1,2-oxathiolane 2-oxides (y-sultines). From cis-1,2-diphenylcyclopropane a mixture of the (2,3-cw)-2-oxide 19 (yield, 52 %) and the (2,3-trans)-2-oxide 20 (yield, 18 %) is obtained... 

Acid-catalyzed dealkoxylation is particularly suitable for the preparation of highly reactive, cationic iron(IV) carbene complexes, which can be used for the cyclopropanation of alkenes [438] (Figure 3.11). Several reagents can be used to catalyze alkoxide abstraction these include tetrafluoroboric acid [457-459], trifluoroacetic acid [443,460], gaseous hydrogen chloride [452,461], trityl salts [434], or trimethylsilyl triflate [24,104,434,441,442,460], In the case of oxidizing acids (e.g. trityl salts) hydride abstraction can compete efficiently with alkoxide abstraction and lead to the formation of alkoxycarbene complexes [178,462] (see Section 2.1.7). 

Gem-dibromocyclopropanes can be converted into synthetically useful cyclopropanone equivalents by a process consisting of lithium-halogen exchange followed by reaction of lithiocyclopropane (113) with dimethyl disulfide (Scheme 43) . The resulting bromo-methylthio derivative (114) undergoes a variety of substitution reactions. Methanolysis gives S,0-dimethylketal (115) which can be converted into l,l bis(methyl-thio)cyclopropane (116) with methyl mercaptan in trifluoroacetic acid. Reaction of 114 with other nucleophiles provides the derivatives shown in Scheme 44 . The sulfur-... 

Arylcyclopropanes are also obtained in good yields by decomposition of aryldiazomethanes with various metals and salts in the presence of an alkene. The reactions do not involve free carbenes, but carbene-metal complexes, and this is probably the reason why the cisjtrans ratios for the arylcyclopropanes vary when the catalyst is changed. Thus, when 4-tolylcarbene, generated by decomposition of 4-tolyldiazomethane with various salts, was allowed to react with (Z)-but-2-ene the cisjtrans ratio of the product, cw-2,3-dimethyl-l-(4-tolyl)cyclopropane (1), varied considerably. When the decomposition is facilitated by trifluoroacetic acid, however, 1 is obtained with a cisjtrans ratio of 1 1. ... 

Several l,l-bis(methylsulfanyl)cyclopropanes have been obtained in high yields by stirring the corresponding 1-methoxy-l-methylsulfanylcyclopropane in trifluoroacetic acid saturated with methanethiol. The reaction proceeds conceivably via a cyclopropyl cation, which is sta-... 

Thus, reaction of cyclopentadienyliron complex 1, containing a cr-bound but-3-enyl unit, with radical or proton-source (e.g. trifluoroacetic acid) reagents leads to regioselective cyclopropane formation with high yields. ... 

When trifluoroacetic acid was added to butylcyclopropane derivatives 12, Markovnikov products were obtained predominantly. Treatment of cyclopropane with concentrated sulfuric acid yielded propanol. With the deuterated acid, D2SO4, deuterium was found at all three carbon atoms presumably due to the formation of a protonated cyclopropane intermediate. When exo-tricyclo[3.2.1.0 ]octane (13) was treated with deuterated sulfuric acid an end-on attack of the deuterium ion at the most strained bond with inversion of configuration to give 14 was observed. 

The trimethylstannylmethyl group facilitates the ring-opening reaction of cyclopropane. When (2-methylcyclopropylmethyl)trimethyltin (37a) in chloroform was treated with electrophiles such as trifluoroacetic acid, iodine, or sulfur dioxide the bond between the methylene and the functionalized methyl group was cleaved preferentially and the trimethyltin group elimin-ated. i- ... 

Treatment of siloxycyclopropanes with acid under more forcing conditions results in further conversion of the initially formed cyclopropanols into the corresponding carbonyl compounds. For example, reaction of l-trimethylsilyl-l-(trimethylsiloxy)cyclopropane (3) with one equivalent of trifluoroacetic acid at 0°C for 15 minutes affords 1-(trimethylsilyl)cyclopropanol (5). Additional reaction for 24 h at 25°C gives ring-opened l-(trimethylsilyl)propan-l-one (4) in 78% yield after vacuum distillation. Desilylation of 3 to the cyclopropanol 5 can also be induced by fluoride ion. ... 

The regiochemistry of ring opening has been examined with 2-methyl-l-(stannyl-methyl)cyclopropane. Thus, the reaction of 2-methyl-l-(stannylmethyl)cyclopropane in chloroform with sulfur dioxide, trifluoroacetic acid, and iodine proceeds preferentially with ring cleavage and addition at the cyclopropane methylene. On the other hand, iodination and acidolysis in methanol proceeds exclusively with Sn —Me bond cleavage. 

Unlike the isomerization of l-chloro[l- C]butane with aluminium trichloride, which proceeds without major participation of protonated cyclo-propanes, the isotopic scrambling from the reaction of [l- C]-l-propyl-mercuric perchlorate in trifluoroacetic acid does require intermediate protonated cyclopropanes. The isolated 1-propyl trifluoroacetate (565) was shown by degradation to have the label distributed as shown in Scheme 76. The greater scrambling from C-1 to C-3 than from C-1 to C-2 requires an edge-rather than a comer-protonated ion. Full details have appeared of the liquid-phase thermolyses of cycloalkyl and cycloalkylmethyl chloroformates which take place via carbonium ions. Protonated cyclopropanes are believed to be intermediates for 5-10% of the products. The alkylation of benzene and toluene by cyclopropane with acidic catalysts also involves initial formation of a protonated cyclopropane. ... 

Microwave spectroscopy studies have provided considerable information on the phenomenon of hydrogen bonding. Earlier studies with conventional microwave spectrometers were on large H-bonded complexes. Typical of these studies is the bimolecule trifluoroacetic acid-cyclopropane carboxylic acid. 

Although cyclopropane formation will be considered in more detail later (section C.4), it is appropriate to mention a rather striking precedent for the proposed intermolecular cationic condensation of (14) to (15) and (16-OPP). The reaction of phenyl diazomethane with excess olefins e.g., /ran5-2-butene) at -70° in the presence of trifluoroacetic acid affords cyclopropanes and benzylated products in fairly high yield (40—60%) along with benzyl trifluoroacetate (30—40%) 62, 63). Cyclopropane formation is stereospecific with cis- and trans-2-butcnc. 

---