Cyclopropane derivatives

Strained cyclic systems such as cyclopropane derivatives proved sensitive to silver ions. Indeed, silver usually induced ring opening of cyclopropanes, leading to argento cationic intermediates, which evolved further depending on substituents. Most, if not all, of these ring rearrangements resulted from initial formation of a a complex of the cyclopropane with silver ion. 

Parallel studies by Masamune et al. led nevertheless to the conclusion that the argento carbonium ion 1 proposed by Paquette et al. may not necessarily be involved in such Ag -catalyzed rearrangements.25 26 

This silver-catalyzed ring rearrangement could be explained by preferential interaction of the silver cation with the most substituted edge of the cyclopropane to form an argento cation. In the latter, the presence of C-Si or Ge bond with the right orientation stabilized the cation sufficiently so that it classically evolved through (3-H 

As one would expect because of the increasing strain, cyclopropenes readily reacted with silver ions, leading to ring-opening products. For example, dialkylcy-clopropenecarboxylates gave mainly E, Zs-dienoates together with some isomers when 

Staal and associates (Staal et al.. 1975 Henrick et al.. 1976) tested a great variety of aliphatic esters containing a cyclopropane moiety as common structural element, such as cyclopropylmethyl carboxylates, cyclopropylmethyl dicarboxylates, alkyl cyclopropanecarboxylates and alkylene biscyclopropanecarboxylates. The most active members of these series were compounds (35), (36), (37) and (38). 

Its acute oral toxicity for rats is 12 200 mg/kg. Two thirds of a single oral dose given to rats was found to be excreted within one day. The major metabolites in tissues are 11-cyclopropyl-undecanoic acid (39), I3-cyclopropy -tridecanoic acid 

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BUTENE. As shown in Figure 38, a group attached to C-1 can migrate from position 1 to 3 (1,3 shift) to produce an isomer. If it is a methyl group, we recover a 1-butene. If it is a hydrogen atom, 2-butene is obtained. A third possible product is the cyclopropane derivative. The photochemical rearrangement of 1-butene was studied extensively both experimentally [88]... 

Whenever functional groups are connected with a C=C double bond, their reactivity is often relayed through that double bond. Analogous rules can be applied to the corresponding cyclopropane derivatives. 

The majority of preparative methods which have been used for obtaining cyclopropane derivatives involve carbene addition to an olefmic bond, if acetylenes are used in the reaction, cyclopropenes are obtained. Heteroatom-substituted or vinyl cydopropanes come from alkenyl bromides or enol acetates (A. de Meijere, 1979 E. J. Corey, 1975 B E. Wenkert, 1970 A). The carbenes needed for cyclopropane syntheses can be obtained in situ by a-elimination of hydrogen halides with strong bases (R. Kdstcr, 1971 E.J. Corey, 1975 B), by copper catalyzed decomposition of diazo compounds (E. Wenkert, 1970 A S.D. Burke, 1979 N.J. Turro, 1966), or by reductive elimination of iodine from gem-diiodides (J. Nishimura, 1969 D. Wen-disch, 1971 J.M. Denis, 1972 H.E. Simmons, 1973 C. Girard, 1974),... 

The growing importance of cyclopropane derivatives (A. de Meijere, 1979), as synthetic intermediates originates in the unique, olefin-like properties of this carbocycle. Cyclopropane derivatives with one or two activating groups are easily opened (see. p. 69f.). Some of these reactions are highly regio- and stereoselective (E. Wenkert, 1970 A, B E. J. Corey, 1956 A, B, 1975 see p. 70). Many appropriately substituted cyclopropane derivatives yield 1,4-difunctional compounds under mild nucleophilic or reductive reaction conditions. Such compounds are especially useful in syntheses of cyclopentenone derivatives and of heterocycles (see also sections 1.13.3 and 4.6.4). 

Allylic acetates react with ketene silyl acetals. In this reaction, in addition to the allylated ester 468, the cyclopropane derivative 469. which is formed by the use of bidentate ligands, is obtained[303]. Formation of a cyclopropane derivative 471 has been observed by the stoichiometric reaction of the 7r-allylpal-... 

What alkenes would you choose as starting materials in order to prepare each of the following cyclopropane derivatives by reaction with lodomethylzmc iodide ... 

Yields m Simmons-Smith reactions are sometimes low Nevertheless because it often provides the only feasible route to a particular cyclopropane derivative it is a valu able addition to the organic chemist s store of synthetic methods... 

Cyclopropane Derivatives. 2,2-Dimethylcyclopropanenitrile [5722-11-2] (4) has been made by preparing the di-/)-toluenesulfonate of neopentyl glycol and treating the diester with potassium cyanide (35). 

In other cases, sulfenic acid elimination can involve y-hydrogen atoms with the formation of cyclopropane derivatives. y-Klimination is favored when DMSO is the reaction solvent. An example involving l-methylsulfinyl-2-ethyl-3-phenyl propane [14198-15-3] is shown in equation 13 (45) ... 

In similar reactions, (12) with carbon—carbon double bonds that are conjugated with carbonyl groups gives cyclopropane derivatives (eq. 24) (48) ... 

Furan and thiophene undergo addition reactions with carbenes. Thus cyclopropane derivatives are obtained from these heterocycles on copper(I) bromide-catalyzed reaction with diazomethane and light-promoted reaction with diazoacetic acid ester (Scheme 41). The copper-catalyzed reaction of pyrrole with diazoacetic acid ester, however, gives a 2-substituted product (Scheme 42). 

While these rearrangements are used most often to prepare large rings, it should be noted that the expansion of cyclopropane derivatives to azetidines is also practical (Scheme 6 Section 5.09.3.3.3.a). 

Pyrolysis at 190° of the resulting diastereomeric A -pyrazolines (8) and (11) leads to elimination of nitrogen and formation of the cis- and tmns-cydo-propanecarboxylates (9) and (12), respectively. Thermal decomposition of the A -pyrazoline (13) affords methyl tiglate (14) in addition to the cyclopropane derivative (15) in a ratio 2 1, while A -pyrazolines such as (3) give only 0L,[i- or, y-unsaturated esters, and no cyclopropane derivatives. 

High vacuum pyrolysis, heating in organic bases, contact with acidic adsorbents and reaction at room temperature with perchloric acid or boron trifluoride etherate cleaves the pyrazoline to give a 45-60% yield of the cyclopropane derivative (13) as well as 9 % of the unsaturated methyl compound (14). ° ... 

Trifluoromethylzinc compounds can be prepared via the direct reaction of dihaloditluoromethane with zinc powder in DMF [J5] (equation 24) In this reaction, the DMF functions both as solvent and reactant Mechanistic experiments support a difluorocarbene reaction intermediate Indeed, a mixture of zinc and difluorodibromomethane in THF has been used for the synthesis of gewi-difluo-ro-cyclopropane derivatives [34 (equaUon 25)... 

Boche, G, Walborsky, H M In Cyclopropane Derived Reactive Intermediates, Fatal, S, Rappoport, Z, Eds, John Wiley Chichester, 1990, Chapter 1... 

Section 14.13 Carbenes aie species that contain a divalent carbon that is, a caibon with only two bonds. One of the chaiacteiistic reactions of caibenes is with alkenes to give cyclopropane derivatives. 

Simmons-Smith reaction (Section 14.12) Reaction of an alkene with iodomethylzinc iodide to form a cyclopropane derivative. 

Epoxidation of aldehydes and ketones is the most profound utility of the Corey-Chaykovsky reaction. As noted in section 1.1.1, for an a,P-unsaturated carbonyl compound, 1 adds preferentially to the olefin to provide the cyclopropane derivative. On the other hand, the more reactive 2 generally undergoes the methylene transfer to the carbonyl, giving rise to the corresponding epoxide. For instance, treatment of P-ionone (26) with 2, derived from trimethylsulfonium chloride and NaOH in the presence of a phase-transfer catalyst Et4BnNCl, gave rise to vinyl epoxide 27 exclusively. ... 

An intriguing rearrangement was reported by Yates (72) during an attempt to carry out the Stobbe condensation. It resulted in the formation of a cyclopropane derivative from 4-benzoyloxycyclohexanone by the (proposed) mechanism shown. 

The preparation of cyclopropane derivatives has been greatly facilitated by the development of carbene-type intermediates (see Chapter 13) and their ready reaction with olefins. The preparation of phenylcyclopropane from styrene and the methylene iodide-zinc reagent proceeds in only modest yield, however, and the classical preparation of cyclopropane derivatives by the decomposition of pyrazolines (first employed by Buchner in 1890) is therefore presented in the procedure as a convenient alternative. 

The cyclopropane derivative 1, formed by the addition of dibromocarbene to 4-ethoxy-l-tosyl-1,2-dihydroquinoline, in refluxing pyridine undergoes ring expansion and aromatization to the 1/f-l-benzazepine 2.168... 

Similar results are observed in the conjugative addition of CH-acidic methylene compounds with the metal derivatives of 2-nitro-5,10,15.20-tetraphenylporphyrin (6). The nickel porphyrin 6 (M = Ni) yields with an excess of dimethyl malonate the cyclopropane derivative 7 whereas the copper porphyrin 6 (M — Cu) forms with two equivalents of malononitrile the bisadduct 8.111... 

In the reaction with epoxides, y-hydroxysulfones are obtained278-280. For example, Kondo and coworkers279 synthesized various (5-lactols 226 by treating sulfone acetals 225 with terminal epoxides as shown below. Dilithiated phenylsulfonylmethylene reacted with haloepoxide and afforded 3-(phenylsulfonyl)cycloalkanols281. Treatment of y, 5-epoxysulfones 227 and 229 with n-butyllithium resulted in cyclization to form cyclopropane derivatives 228 and bicyclobutane 230, respectively282. 

Other reactions involving a-sulfonyl carbanions which afford cyclopropane derivatives or aromatic rings can be seen in the examples comprising Scheme 8392 400. 

Treatment of a-lithionitriles with vinylic sulfones resulted in the formation of cyclized products, i.e., 3-oxothian-l, 1-dioxides 346 or cyclopropane derivatives 348. When a-lithiated aliphatic nitriles were used, carbanions 343, formed by the nucleophilic addition,... 

Non-heteroatom-stabilised Fischer carbene complexes also react with alkenes to give mixtures of olefin metathesis products and cyclopropane derivatives which are frequently the minor reaction products [19]. Furthermore, non-heteroatom-stabilised vinylcarbene complexes, generated in situ by reaction of an alkoxy- or aminocarbene complex with an alkyne, are able to react with different types of alkenes in an intramolecular or intermolecular process to produce bicyclic compounds containing a cyclopropane ring [20]. 

Stabilised sulphur ylides react with alkenylcarbene complexes to form a mixture of different products depending on the reaction conditions. However, at -40 °C the reaction results in the formation of almost equimolecular amounts of vinyl ethers and diastereomeric cyclopropane derivatives. These cyclopropane products are derived from a formal [2C+1S] cycloaddition reaction and the mechanism that explains its formation implies an initial 1,4-addition to form a zwitterionic intermediate followed by cyclisation. Oxidation of the formed complex renders the final products [30] (Scheme 8). 

Alkenylcarbene complexes react with in situ-generated iodomethyllithium or dibromomethyllithium, at low temperature, to produce cydopropylcarbene complexes in a formal [2C+1S] cycloaddition reaction. This reaction is highly diastereoselective and the use of chiral alkenylcarbene complexes derived from (-)-8-phenylmenthol has allowed the enantioselective synthesis of highly interesting 1,2-disubstituted and 1,2,3-trisubstituted cyclopropane derivatives [31] (Scheme 9). As in the precedent example, this reaction is supposed to proceed through an initial 1,4-addition of the corresponding halomethyllithium derivative to the alkenylcarbene complex, followed by a spontaneous y-elimi-nation of lithium halide to produce the final cydopropylcarbene complexes. 

Woodworth, based on the common reaction of addition of carbenes to double bonds to form cyclopropane derivatives (15-50). If the singlet species adds to cis-2-butene, the resulting cyclopropane should be the cis isomer since the movements of the two pairs of... 

Radicals are known to open cyclopropane derivatives, although high dilution techniques are often required. The three-membered ring is opened as the new ring... 

Carbenes and substituted carbenes add to double bonds to give cyclopropane derivatives ([1 -f 2]-cycloaddition). Many derivatives of carbene (e.g., PhCH, ROCH) ° and Me2C=C, and C(CN)2, have been added to double bonds, but the reaction is most often performed with CH2 itself, with halo and dihalocarbenes, " and with carbalkoxycarbenes (generated from diazoacetic esters). Alkylcarbenes (HCR) have been added to alkenes, but more often these rearrange to give alkenes (p. 252). The carbene can be generated in any of the ways normally used (p. 249). However, most reactions in which a cyclopropane is formed by treatment of an alkene with a carbene precursor do not actually involve free carbene... 

Alkenes of all types can be converted to cyclopropane derivatives by this reaction (though difficulty may be encountered with sterically hindered ones). Even tetracyanoethylene, which responds very poorly to electrophilic attack, gives cyclopropane derivatives with carbenes.Conjugated dienes give 1,2 addition ... 

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