Cyclopropyl substituent

An analogous cyclization to eventually form five-membered rings has also been observed for l-metalla-l,3,5-hexatrienes with an additional heteroatom within the chain, such as in the complexes 157. These are obtained by Michael additions of imines to alkynylcarbene complexes in good to excellent yields (reaction type F in Scheme 4), and their configurations were determined to be Z (>91%) in all cases. Upon warming in THF solution, complexes 157 underwent cyclization with reductive elimination to furnish 2Ff-pyrroles 158 in up to 97% yield (Scheme 34). With two cyclopropyl substituents at the terminus in... 

Surprising is the absence of evidence for additional stability of 85 over 83. Electron donation from the electron-rich a bonds of the cyclopropyl ring to the carbene s vacant p orbital is widely believed to stabilize cyclopropylcarbenes.4 One would therefore expect 85, with an additional cyclopropyl substituent, to react more slowly than either parent carbene 83 or dimethylcarbene, but all three lifetimes are comparable. The lifetimes of 83-85 need to be redetermined in inert (fluorocarbon) solvents in order to reveal their innate differences. Note, however, that the effect of cyclopropyl substitution is apparent upon comparison of 83 (r 24 ns) to MeCH (r < 0.5 ns).89110... 

Numerous y-secretase inhibitors featuring sulfonamide- and sulfone-based scaffolds have been disclosed. Bicyclononane thiophene sulfonamide 40 reduced brain Ap in transgenic mice by 50% after a dose of 100 mg/kg [100]. High potency (A p IC50 = 0.5 nM) and improved oral activity (ID50 = 17 mg/kg) was found in a series of related sulfamides represented by 41 [101]. Tetrahydroquinoline (42) and piperidine (43-44) sulfonamides have been developed [102-104]. Elaboration of the piperidine series with the cyclopropyl substituent present in 44 improved in vitro potency (Aft IC50 = 2.1 nM in membrane assay) and in vivo activity in transgenic mice (plasma Ap = 2% of control after oral dose of 30 mg/kg). Reductions of A p in the cortex were reported to be comparable to those observed in plasma. 

Cyclization of substrates containing a cyclopropyl substituent proceeds with concomitant cleavage of the cyclopropyl ring. 

For other structure-activity relationship of the quinolone antibacterials improved by the presence of cyclopropyl substituents see Ref. [212]. 

When dihalocyclopropanes carrying a cyclopropyl substituent are thermolyzed both rings are opened and substituted 1,3-hexadienes are formed. 

Schier and Schmidbaur93 performed a clever experiment that addressed part of this question does the orientation of the carbanion relative to the phosphorus atom play any role Scheme 2 shows two syntheses of ylides involving cyclopropyl substituents. In the first reaction, since the pKa of cyclopropane is considerably below that of propane, the expected product is the cyclopropylide. However, the isopropylide is the only recovered product. The second reaction also demonstrates the avoidance of the cyclopropylide product. The cyclopropylide possesses a very pyramidal carbanion that is directed away from phosphorus, allowing for minimal orbital overlap. The isopropylide is much less pyramidal and phosphorus can better assist in stabilizing the carbanion. While this stabilization does not require explicit orbital overlap (the electrostatic interaction of the carbanion with the onium is expected to be smaller in the cyclopropylide since it is directed away from P), it does suggest that some orbital interactions are involved. Hence, although the ylene contribution is small, it is unlikely that the ylene contribution is nil. 

Further reduction in R leads to the point Rc (Figure 3) at which the bond is fully formed and normal cyclopropyl substituent interactions occur. Homoconjugation ceases to be a relevant chemical factor at point Rc and the molecule can be adequately described in terms of a cyclopropyl substituted system. 

An interesting point is that up till now it has been very difficult to prepare complexes containing the six electron donor mode with other substituents on the rf -bonded C=N unit. The only exception is MnCo(CO)6(Prc-DAB Me,Me ) with a cyclopropyl substituent on the N atoms.137 No doubt steric reasons are important but it should be noted that in the case of the eight electron donor mode for R-DAB R, R" stable complexes could also be obtained for R = R" = Me.158... 

The 13 C NMR chemical shifts of the para carbon for various phenyl-substituted sp2-and sp-hybridized carbocations (Figure 15) indicate that the demand for rr-aryl delocalization of the positive charge for the -silyl-substituted vinyl cation 393 is lower compared with that in a-phenylethyl (78), a-methyl-a-phenylpropyl (397) and cumyl (292) cations150 153. The stabilizing effect of the /)-silyl group in 393 is comparable to that of the cyclopropyl substituent in 1-cyclopropylbenzyl cation (398). The para carbon shift in the /)-cr-silyl... 

There has been considerable interest in ring opening of cyclopropyl-containing ketyl anions from both a mechanistic and synthetic viewpoint. Cyclopropyl substituents are often... 

Similar results are obtained for the corresponding tosylates 281).In conforma-tionally nonrigid systems, on the other hand, where the preferred bisected (97) conformation may be adopted, cyclopropyl substituents enhance solvolysis rates by a factor of approximately 104 30S). Therefore, a free energy difference between 97 and 98 of about 10 kcal/mole (1.36 log 107) may be estimated for tertiary cyclopropylcarbinyl cations at 25 °C28°). 

Upon treatment with an ethereal solution of methyllithium, both oligocydopropyl-substituted cyclopentadienes 14 and 6 in tetrahydrofuran were quantitatively deprotonated to the corresponding cyclopentadienides 14-Li and 6-Li, respectively, which were characterized by their 1H and 13 C NMR spectra. Treatment of the solutions of 14-Li and 6-Li with solutions of iron(II) chloride in tetrahydrofuran yielded the l,l, 2,2, 3,3, 4,4 -octacydopropylferrocene (16) (74%) and the decacyclopropylferrocene (17) (21%). After crystallization from hexane (for 16) and pentane/dichloromethane (for 17), the structures of both ferrocenes were established by X-ray crystal structure analyses (Scheme 3). The electron-donating effect of the cyclopropyl substituents on these cyclopentadiene systems is manifested in the oxidation potentials of the ferrocenes 16 and 17. While the parent ferrocene has an oxidation potential E1/2 (vs. SCE) = +0.475 V, that of decamethylferrocene is significantly lower with Ei/2 = —0.07 V, and so are those of 16 (Ey2 — —0.01 V) and 17 (f i/2 = —0.13 V) [13]. 

When the double bond of the enyne possesses a cyclopropyl substituent, an intramolecular [5+2] cycloaddition of alkyne and vinylcyclopropane takes place [75, 76]. The ruthenacycle does not undergo /l-hydride elimination but a rearrangement of the cyclopropane to produce a ruthenacyclooctadiene. Thus, a variety of bicyclic and tricyclic cycloheptadienes were obtained in good yields [75] (Eq. 55). 

One case where C—C bonds are exceptionally effective in hyperconjugation is in the stabilisation provided by a cyclopropyl substituent to an empty p orbital. The cyclopropylmethyl cation is actually better stabilised than an allyl cation, as judged by the more rapid ionisation of cyclopropylmethyl chloride 2.19 than of crotyl chloride 2.20. In this case, hyperconjugation appears, unusually, to be better than n conjugation. 

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