Cyclopropanes fluoro

The violence of superbasic slurries towards functionalized organic molecules means that they are at their most effective with simple hydrocarbons they also tolerate ethers and fluoro substituents. LiCKOR will deprotonate allyUc, benzylic, vinylic, aromatic and cyclopropane C—H bonds with no additional assistance. From benzene, for example, it forms a mixture of mono and dimetallated compounds 617 and 618 (Scheme 241) . ( Li/K indicates metallation with a structurally ill-defined mixture of lithium and potassium.)... 

We have examined the above-described series of trans- and c/s-2-fluoro-2-phenylcyclopropylamine analogues (60a-d, 61a-d) as inhibitors of recombinant human liver MAO A and B [134]. The presence of fluorine attached to a cyclopropane ring, especially for frans-isomer 8a, was found to result in an increase in inhibitory activity toward both MAO A and B (Table 4). In addition, p-substitution of electron-withdrawing groups, such as Cl and F, in the aromatic ring of the frans-isomers (60b-d) increased the inhibition of both enzymes. On the other hand, the introduction of fluorine at 2-position of c/s-isomer 8b resulted in loss of inhibitory activity for both MAO A and B, and no further p-aromatic substitution for c/s-isomer greatly affected on the inhibitory activity with either enzymes. In addition, both MAO A and B were selectively inhibited by the (1S,2S)-enantiomer of 60a, while no inhibition was observed with the (1f ,2f )-enantiomer [134]. As already described in the former section, several questions on the mechanistic pathway for MAO inhibition by cyclopropylamines still remain. However,... 

The cyclopropanation of a chiral enamide has been investigated for the preparation of fluoro-substituted cyclopropylamines. Unfortunately, the reaction produced a mixture of all four possible stereoisomers when the chiral starting material was submitted to the a-fluoro iodomethylzinc carbene (equation 80). ... 

The increasing tendency toward thermal extrusion of CF2 with increasing number of fluorine substituents on the cyclopropane ring has been demonstrated in studies of 1,1-difluorocyclo-propane, 1,1,2-trifluorocyclopropane, 1,1.2,2-tetrafluorocyclopropane,19 and perfluorocyclo-propane.20 Studies of the thermolysis of 1,1,2,2-tetrafluorospiropentane 8 21 and 1,1.2,2-tetra-fluoro-3-methylenecyclopropane (25),22 however, demonstrated that the CF2-CF2 bond in a tetrafluorocyclopropane is substantially weakened. In the case of 25, rearrangement to 2-(di-fluoromethylene)-l,l-difluorocyclopropane (26) occurs irreversibly at 150°C at a rate that was calculated to be 7850 times faster than that of the gem-difluoro analog 21. 

I-Butene 4.4-Dichloro-4-fluoro-l-phenyl- ElOa. Ill [(1-OH-alkyl) — cyclopropane + HF]... 

Cyclopropane (Continuation) 2-ButyI-l-fiuorol -(4-melhoxy-phenyl)- ElOb,. 504 (En + F —C — Ar) 2-Bulyl-l-fluoro-1-phcnoxv- EI7a. 

Fluoro-3-nitro- ElOa. 625 (Cyclopropane + 02N BF ) Fluoro-oxo- ElOa. 683 (H -> F)... 

Perfluorocyclopropene reacts readily with sodium methoxide at low temperature [22] (equation 19) Slow addition of sodium methoxide to 1,2 dichloro-3,3-di fluorocyclopropane yields initially l-chloro-2-methoxy-3,3-difluorocyclopro pane Further addition of methanol produces probably a ketal Opening of the cyclopropane ring gives an ortho ester that undergoes facile hydrolysis during the workup to form (Z)-methyl 2-fluoro-3-chloroacrylate [23] (equation 20) A per-fluorocyclobutene dimer is also very reactive and undergoes an easy SN2 displacement on treatment with ethanol [24] (equation 21)... 

Extensive gas-phase structural studies have been performed on fluoro-substituted cyclopropanes. Important structural parameters are collected in Table 9. 

A fluorine substituent shortens the adjacent C—C bonds and lengthens the opposite bond in the cyclopropane ring. The lengthening of the C—C bond opposite to a CF2 group is remarkable (cf 98 and 104 in Table 9), but the mean C—C distance is smaller even in these molecules than in cyclopropane (1). In the other fluoro derivatives, all C—C bonds are shorter than in 1. The C—C bonds appear to be longer, the C—F bonds shorter in a cis isomer than in the trans isomer , and the same applies to C—C and C—F bonds in cis compared to trans CHF—CHF moieties within the same molecule. Ab initio calculations with a 4-2IG split valence basis set reflect the above trends quite well, except for the distinction of effects in the cis and trans forms ". The additivity of substituent effects, which... 

Substituted fluorocarbenes, for example, arylfluorocarbenes 1, (alkoxycarbonyl)fluorocar-benes 2. fluoro(trichlorovinyl)carbene (3). fluoro(trifluoromethyl)carbenc (4). and (difluoromethyl)fluorocarbene (5), have been reported. Their addition to alkenes to give fluo-rinated cyclopropanes has been studied (see Table 2). 

Cyclopropane 2-Chloro-2-fluoro-l-methyl-l-(trimethylsilyl-methyl)-E10 (En + CFC1)... 

Tetraline l-(Dibromo-methylen)-2-fluoro- E10 (R3Si - O —cyclopropane -> En —CH2 —F)... 

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