Nitrocyclopropanes

Both N02 groups take the bisected conformation in the crystal the C—N02 bond lengths are different, 1.474 (7) and 1.452 (7) A. 

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Nitrocyclopropane-l-carboxylate is prepared in 71% yield by nitration of the enolate derived from the cyclopropane carboxylate with isoamyl nitrate (Eq. 2.24). It is a precursor of... 

Bromonitromethane is used for the preparation of nitrocyclopropane. The reaction of /V-be 11 zylmaleimide and bromonitromethane in the presence of base gives the azabicyclo[3.1.0] hexane ring system. Many bases have been tried to improve the yield however, amidine base, particularly 1,2-dimethyl-l, 4, 5, 6-tetrahydropyrimidine (DMTHP), gives the best yield... 

In all the above examples, the synthesis of nitronates (5) is rather chemose-lective. In any case, data on the formation of their structural isomers, viz, the corresponding nitrocyclopropanes (13), are lacking. However, the synthesis of five-membered nitronates (5) with the use of sulfur or selenium ylides is not chemoselective (see Scheme 3.16). 

The process shown in Scheme 3.16 is rather interesting. It should be noted that in most cases this reaction is very stereoselective with respect to the arrangement of the substituents at C-4 and C-5 atoms. In light of recent data on the possible isomerization of nitrocyclopropanes (13) to form five-membered cyclic nitronates (5) (for more details, see Section 3.2.2.1.2), low chemoselectivity of many reactions involving sulfur ylides does not seem to be so fatal. 

Unfortunately, only two attempts were made to use this approach in the synthesis of five-membered cyclic nitronates (5), and only one of them could be considered as successful. In the latter case, isomeric nitrocyclopropane was obtained as the major product. Only a-functionalized nitro alcohols are readily involved in the Mitsunobu cyclization. However, the possibility of isomerization of by-products, nitrocyclopropanes, which was mentioned in the discussion of Scheme 3.16, caused the revision of this process as a procedure for the synthesis of five-membered cyclic nitronates. (A new approach to the synthesis of initial y-nitro alcohols from readily available AN was documented in Reference 64)... 

In addition to conventional generation of carbenes from nitrodiazo compounds (22) (79), target intermediates C can be prepared by oxidation of functionalized AN CH2XNO2 with phenyliodonium diacetate. The reactions of Rhodium intermediates with certain olefins afford the corresponding cyclopropanes (23). The cycloaddition reaction was performed in the presence of a catalyst. (The successful synthesis of nitrocyclopropanes from trinitromethane derivatives and nitroacetic ester was also documented (81)). 

Therefore, all prerequisites are present for the development of a general strategy for the synthesis of nitronates (24) from a-functionalized primary AN through stabilized carbenium intermediates and nitrocyclopropanes (23). This approach allows the stereoselective synthesis of nitronates (24) from simple molecules (Scheme 3.29). 

Cycloaddition of Carbenes to conjugated Nitro Olefins (28). From the above it is evident that there is another synthetic route to nitronates (24 g) with the use of carbenium intermediates based on [1 + 2]-cycloaddition of carbenes RR C to conjugated nitro olefins (28) followed by isomerization of intermediate nitrocyclopropanes (23 g). However, this strategy was used only in one study (see Scheme 3.30). 

Die Synthesen der meisten einfachen Cyclopropanderivate konnten im Laufe der letzten Jahre verbessert werden. Cyclopropanol, Cyclo-propylbromid und Nitrocyclopropan wurden erstmals dargestellt. 

Nitrocyclopropan entsteht nach Hass und Shechter (95) bei der Nitrierung von Cyclopropan in der Gasphase bei 335 bis 390°. Die bislang unbekannte Verbindung konnte durch Reduktion zum Cyclo-... 

The fused dicyclopropane (12) has been synthesized by treating nitrocyclopropane (11) with lithium diisopropylamine in THF at low temperature. ... 

Other types of conjugate additions with chiral thioureas were also explored by Connon. P-Substituted nitro-olefms were used in the conjugate addition reaction with dimethyl chloromalonate 115 to generate chiral, functionalized nitrocyclopro-panes [73]. Utility of the nitrocyclopropanes was demonstrated in the one-step modification towards other functionalized chiral building blocks (Scheme 24). 

Spurred by these observations, we examined a relevant application of the method for nitrocyclopropane synthesis from nitroalkenes and dimethylsulfoxonium methylide (17), Equation 3. It had previously been employed for the synthesis of a 2,3-dideoxv-2,3-C-methylene-3-nitro-hexopyranoside, the first one of the small number of carhohvdrates containing the nitrocyclopropane structure thus far known (18). 

Figure 8. Formation of a carbohydrate nitrocyclopropane from a nitroalkenic sugar via a pyrazoline.

Scheme 6.121 Nitrocyclopropanes obtained from 122-catalyzed Michael addition of dimethyl chloromalonate to frans-P-nitroalkenes and subsequent DBU-promoted cyclization.

A -compounds (130) with CH2NO2 leads to the nitrocyclopropanes (131) by Michael addition and elimination of HBr. Various transformations of the la-nitromethyl-3-oxo-compounds (132) include its conversion into the la-formyl-3-oxo-compound (133), which on hydride reduction was converted into the tetra-hydrofuran (134). ... 

In an analogous manner, nitroalkenes can be utilized as the electrophile in a tandem coupling-cyclization process (Eq. 2.18). Addition of a stabilized sulfonium ylide such as 209, to a variety of nitroalkenes provides an intermediate nitronic acid, which upon displacement of dimethyl sulfide provides a mixture of the corresponding nitrocyclopropane (XL) and cyclic nitronate (XLI). The ratio of products is highly dependent on the structure of the nitroalkene. For example, without a substituent on the a-position of the nitroalkene (R = H), only the... 

A variety of three-membered carbocycles including cyclopropylcarbonyl and -sulfonyl derivatives, cyclopropylcarbonitriles and -methanols, nitrocyclopropanes, cyclo-propanols and cyclopropylamines have been prepared via the 1,3-elimination of HX. Some representative cyclopropyl derivatives recently prepared by this method are shown in Scheme 116-18 and in equations 8-26. Conversion of chelated homoserine, 5,to chelated 2-amino-4-bromobutyrate and treatment with aqueous base directly affords chelated 1-aminocyclopropane-l-carboxylate (equation 8)19. The 1,3-elimination in 6 interestingly leads to the preferential formation of the cis isomer, from which 7, a key structural element of synthetic pyrethroid insecticides, is obtained (equation 9)20. A sulfur substituent can serve both as an activating group and as a leaving group in this type of reaction and, thus, 1,3-bis(phenylthio)propane affords cyclopropyl phenyl sulfide upon treatment with butyl-... 

Treatment of y-nitro alcohols with diethyl azodicarboxylate DEAD and triphenylphos-phine affords nitrocyclopropanes with inversion of configuration at the a-carbon via the intramolecular Mitsunobu reaction involving carbon nucleophiles stabilized by the nitro group (equation 16)28. The reaction works best with nitro compounds (pA"a < 17) and is not applicable to the sulfonyl derivatives (pATa 25). 

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