Trans-Cyclopropane

Attempts to increase the diastereoselectivity by a more rigid cyclopropane backbone were not successful. However, the incorporation of racemic trans-cyclopropane carboxylate 35 is completely regioselective, and both diastereomeric products 36 were isolated in a ratio of 4.1 1 [39] (Scheme 23). 

The cz5-aziridine substrate shows, as expected on the basis of this model, predominant formation of the trans-cyclopropane product. The starting materials for this MIRC reaction can readily be obtained from the aziridine esters by reduction to the corresponding aldehyde and a subsequent Knoevenagel reaction with malonate ester (Scheme 25) [34]. 

These two compounds with S configuration on their oxazohne rings were tested as copper(I) catalysts for the cyclopropanation of styrene, the hgand 9 with S axial chirality being much more enantioselective than 10 with the R configuration. Thus, the catalytic system CuOTf-(S,S)-bis(oxazolyl)-binaphthyl (9, R = Bu) led to excellent enantioselectivities, particularly for the cyclopropanation of styrene with (-menthyldiazoacetate 95% ee for the trans-cyclopropane and 97% ee for the cis, with trans/cis = 68/32. 

The solids were used as catalysts in the benchmark cyclopropanation reaction between styrene and ethyl diazoacetate (Scheme 7). As far as the nature of the clay is concerned, laponite was foimd to be the best support for the catalytic complexes. The best enantioselectivity results (Table 7) were obtained with ligand 6b (69% ee in trans cyclopropanes and 64% ee in cis cyclopropanes) but the recovered solid showed a lower activity and enantioselectivity, which was attributed to partial loss of the chiral ligand from the support. In general, the use of the three chiral ligands led to enantioselectivity results that were intermediate between those obtained in homogeneous phase with CuCl2 and Cu(OTf)2 as catalyst precursors. This seemed to indicate that the sohd behaved as a counterion with an intermediate coordinating abihty to the copper centers. 

It is concluded from these results that with this kind of non-C2 symmetric ligand (that led necessarily to poor enantioselectivities in homogeneous phase), it is possible to exploit support effects to change the trans/cis selectivity and to improve the enantioselectivity. This is demonstrated for the trans-cyclopropanes obtained with ligand 10a in styrene. Due to the relative disposition of the ester and phenyl groups in the transition state, support ef-... 

The starting material was trans-cyclopropane-1,2-dimethanol. The contiguous cyclopropane units were added by two iterative sequences of oxidation-Wadsworth-Emmons reduction-cyclopropanation. 

Brunner and Berghofer (48) investigated ligands composed of a combination of salicylaldimines and oxazolines. Intriguing effects of the electronic character of the phenol were noted. The electron poor p-nitrophenol 74b provided the trans cyclopropane in 53% ee, compared to 6% ee using the parent phenol ligand 74a. 

The experimental ratio of ds- to trans-cyclopropane 43 46, i.e. the stereo-specifity of the reaction cannot be considered as a simple indication of singlet or triplet percentage of RaC , since the stereochemistry of the cyclo-addition depends on many factors. Photolysis produces the exdted 5i-state of the diazoalkane 41. This compound can lose nitrogen and form the singlet carbene 42 (So-state). 42 can add directly in a stereospecific manner if ki is large. If, however, intersystem crossing 42 45 (Aisc is large) competes favorably with... 

The dilution technique makes use of the different concentration dependence of a) S-T-intersystem crossing, and b) [1 -f-2]-cyclo-addition of a carbene to an olefin. The decay of the metastable singlet state is monomolecular, while the stereospecific addition is of the first order with respect to the concentration At high dilution with an inert solvent such as hexafluorobenzene or octafluoro-cyclobutane etc., the same cis-/trans-cyclopropane ratio should be obtained with cis- or trans-olefin as the starting compound. 

The photolysis of diphenyl-diazomethane in cis-jS-deutero-styrene, on the other hand, can be affected by dilution with hexafluorobenzene. The amount of trans-cyclopropane 49 is slightly larger, indicating that about 12% of the singlet carbene are still present in very dilute solutions (see Table 9). 

The yield of trans-cyclopropane 54 produced by addition of carbena-cyclo-hexadienone 52 to cis-2-butene increases from 5 to 33% if 90% CeFe is added 3 ). 

A flask is charged with finely powdered molecular sieves (4 A, 50 mg), magnesium turnings (97 mg, 4.0 mmol), titanocene dichloride (249 mg, 1.0 mmol), THE (5 mL), triethyl phosphite (0.34 mL, 326 mg, 2.0 mmol) and 1-octene (224 mg, 2.0 mmol), in the order given. The resulting mixture is stirred for 2 h at room temperature and a solution of 2 [( )-2-phenylethenyl]-l,3-dithiane (111 mg, 0.5 mmol) in THF (2 mL) is added. The mixture is stirred for 4 h and then diluted with hexane (30 mL). Filtration through Celite, concentration of the filtrate, and purification of the product by preparative TLC gives 82 mg (72%) of the title compound as a mixture of cis and trans cyclopropanes (cis/trans 60 40). 

Successive treatment of (-(-dimethyl succinate with LiTMP and bromochloromethane provides (S, S)-trans-cyclopropane-1,2-dicarboxylic ester in 99% de (equation 145)324. 

With modified Aratani catalysts (2, R = Ph and A = CH2Ph), Reissig observed moderate enantioselectivities (30-40% ee for the trans cyclopropane isomer) for reactions between trimethylsilyl vinyl ethers and methyl diazoacetate [26], but vinyl ethers are the most reactive olefins towards cyclopropanation and also the least selective [30,31]. Other chiral Schiff bases have been examined for enantio-selection by using the in situ method for catalyst preparation that was pioneered by Brunner, but enantioselectivities were generally low [32]. 

The C2-symmetric 2,6-bis(2-oxazolin-2-yl)pyridine (pybox) ligand was originally applied with Rh for enantioselective hydrosilylation of ketones [79], but Nishiyama, Itoh, and co-workers have used the chiral pybox ligands with Ru(II) as an effective cyclopropanation catalyst 31 [80]. The advantages in the use of this catalyst are the high enantiocontrol in product formation (>95 % ee) and the exceptional diastereocontrol for production of the trans-cyclopropane isomer (>92 8) in reactions of diazoacetates with monosubstituted olefins. Electronic influences from 4-substituents of pyridine in 31 affect relative reactivity (p = +1.53) and enantioselectivity, but not diastereoselectivity [81]. The disadvantage in the use of these catalysts, at least for synthetic purposes, is their sluggish reactivity. In fact, the stability of the intermediate metal carbene has allowed their isolation in two cases [82]. 

The reagent reacts with a,(3-enones and a, 3-unsaturated esters to form trans-cyclopropanes, such as 2 and 3. 

A ring system that is able to restrict conformational flexibility while minimizing additional bulk is cyclopropane. As a strained system, its angles differ from the standard 60° and 180° possibilities with cyclohexane. The (+)-trans cyclopropane analogue (9.26) does show muscarinic activity comparable to acetylcholine (Figure 9.13). The dihedral angle between the ester and ammonium group is approximately 145°. The (—)-trans enantiomer and both... 

The sulfoxonium ylid 78 is more stable and is therefore liable to do conjugate rather than direct addition (chapter 21). The intermediate eliminates dimethyl sulfoxide 79 to give the cyclopropane 76. The intermediate is long lived and the single bond that was the alkene can rotate so the geometry of the alkene is lost. In this case we expect the more stable trans cyclopropane to be formed by choice. 

Eliminative cyclization.1 Treatment of the ailyiic phosphate ester 1 with this strong base results in eliminative cyclization to the trans-cyclopropane 2, the marine... 

Insecticides of the pyrethroid class, such as trans-chrysanthemic acid (190), have significant commercial value (see Chapter 31).241 An asymmetric synthesis of 190 has been achieved through the use of a chiral copper carbenoid reaction (Scheme 12.77).242 243 With ethyl diazoacetate, equal amounts of the cis- and trans-cyclopropanes were formed. However, when the size of the alkyl... 

Because the process is concerted, we expect that the geometry of the alkene should be preserved in the product—the reaction ought to be stereospecific. The two examples below show that this is indeed the case. It is more impressive that the Z-alkene gives the cis cyclopropane as this is less stable than the trans cyclopropane and would change if it could. 

Hammond and Cole reported the first asymmetric photosensitized geometri-r cal isomerization with 1,2-diphenylcyclopropane (Scheme 2) [29]. The irradiation of racemic trans-1,2-diphenylcylcopropane 2 in the presence of the chiral sensitizer (R)-N-acetyl-1 -naphthylethylamine 4 led to the induction of optical activity in the irradiated solution, along with the simultaneous formation of the cis isomer 3. The enantiomeric excess of the trans-cyclopropane was about 1% in this reaction. Since then, several reports have appeared on this enantiodifferentiating photosensitization using several optically active aromatic ketones as shown in Scheme 2 [30-36]. The enantiomeric excesses obtained in all these reactions have been low. Another example of a photosensitized geometrical isomerization is the Z-E photoisomerization of cyclooctene 5, sensitized by optically active (poly)alkyl-benzene(poly)carboxylates (Scheme 3) [37-52]. Further examples and more detailed discussion are to be found in Chap. 4. 

The reaction gives cyclopropane derivatives in a stereospecific way 112, 121, 456, 457, 459). Reactions with cis- and frawj-olefins give the corresponding ds- and trans-cyclopropane derivatives, respectively. The... 

When each stereoisomeric reactant forms a different stereoisomeric product the reaction is known as stereospecific reaction. For example, the addition of CBr2 (dibromo-carbene, prepared from bromoform and base) to ds-2-butene gives cis-2,3-dimethyl-l,l-dibromocyclopropane (1.32), whereas addition of CBr2 to the trans-isomer exclusively yields the trans-cyclopropane 1.33. 

Thus, cis-alkene reacts with singlet carbene to give ds-cyclopropane, and trans-alkene gives trans-cyclopropane (Scheme 2.53). 

However, triple carbene reacts with ds-alkene or trans-alkene. to give a mixture of cis-and trans-cyclopropanes (Scheme 2.54). 

It has been found that the reaction of dimethyloxosulfonium methylide and diazomethane with (E)-3-aryl-2-phosphonoacrylates (346) using the (-)-S-phenyl-menthyl group as a chiral auxiliary gives the trans cyclopropane derivatives with high diastereoselectivity. This can be attributed to the high Jt-face differentiation of the acrylate moiety by the face-to-face interaction with the phenyl ring of the chiral auxiliary in the s-cis conformer. On the other hand, (Z)-isomers of (346) gave a mixture of cis and trans cyclopropane derivatives with low diastereoselectivity (Scheme 93). ... 

Determinations of absolute configurations of trans-cyclopropane-l,2-dicarboxylic acids on the basis of a definite Cotton effect seem to be possible for carboxylic acid thioamides. In these molecules, such as 123a and 123b, there is a Cotton effect near 330 nm which results from the (n, n ) excitation of the thioamide chromophore . In the... 

The free radical chain mechanism of the addition reaction of bromodicyanomethane to alkenes has been corroborated by inhibition experiments with oxygen and t-butylcatechol. The mechanism of equation 66 has been postulated. The ring-closure of the 2-bromoalkylmalononitriles gives rise to mixtures of cis- and trans-cyclopropanes. 

Similar results have been observed when the reaction was started with the thermodynamically more stable trans-cyclopropane trans-178a, and at different temperatures. Obviously, two different reactions take place ... 

Since the corresponding cis,cis-isomer 318 with potassium t-butoxide in DMSO-d led to the tris-deuterated trans,trans-cyclopropane 3I6-D3 Mulvaney and Savage concluded that the 1,2,3-triphenylcyclopropyl anion is capable of existing for a finite period of time as an intermediate without undergoing ring-opening. Therefore this cyclopropyl anion... 

Despite these enormous experimental difficulties, Berson and Pedersen accomplished the task, using trans-cyclopropane-l,2-d2. The synthesis was carried out as described in Section II. The analysis of cis-trans isomer ratios was effected by quantitative IR spectrometry, and the rotations were measured on the pure liquid cyclopropane in a specially designed cell. 

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