Substitution 1,2,3-trisubstituted cyclopropanes

Substituted allylic ethers were transformed predominantly into trans-1,2-di- and -1,1,2-trisubstituted cyclopropanes (Table 6). The degree of trans selectivity depends on the OR group, and is higher with R=Me than with Bn (entries 1 and 2), the diastereoselectivity being generated in the hydro-zirconation step [29]. Furthermore, the cyclization step proceeds with the inversion of the configuration at the carbon atom bound to zirconium [30]. 

Enantioselective Synthesis of 1,2,3-trisubstituted Cycio propanes. The chiral dioxaborolane ligand can also be used to generate 1,2,3-substituted cyclopropyl units when the appropriate 1,1-diiodoalkane is used in the preparation of the zinc reagent (eq 9). The reaction affords 1,2,3-trisubstituted cyclopropanes with excellent enantio- and diastereocontrol, including those obtained from functionalized zinc reagents (eq 10). 

Only a few results are available concerning competitive cyclopropanation of non-conjugated dienes. The case of 1,4-hexadiene72 (mixture of Z and E isomers) illustrates the reactivity difference between a monosubstituted and a 1,2-disubstituted double bond, whereas in limonene (24)47, a 1,1-disubstituted and a trisubstituted double bond compete for the carbenoid derived from ethyl diazoacetate. In both cases, the less substituted double bond reacts preferentially (Scheme 8). 

Lowenthal and Masamune (44) investigated the cyclopropanation of trisubsti-tuted alkenes leading to a chrysanthemic acid synthesis. They found that ligand 50c provided poor selectivities in this case (24% de for the trans isomer). Substitution in the 5 position of the oxazolines leads to increased selectivities, with excellent results provided by the BHT ester (94 6, 94% ee), Eq. 32. This ligand proved to be applicable to other trisubstituted and several cis-disubstituted alkenes, providing the corresponding cyclopropanes in ee values of 82-95%. These authors note that catalysts generated from CuOTf, CuOf-Bu, and Cu(II) precursors (with activation) provided similar yields and enantioselectivities. 

The photochemical extrusion of nitrogen from silyl-substituted diazoacetates (hv > 300 nm) in the presence of various alkenes leads mainly to the formation of cyclopropanes (Table 4). Reactions of trimethylsilyl- and triisopropylsilyldiazoacetates with monosubstituted alkenes such as hex-1-ene or styrene (Table 4, entries 1-3) show interesting results. The formation of the thermodynamically less favored Z-isomer increases with growing steric demand of the silyl substituent. The cyclopropanation of ( )- and (Z)-but-2-ene (Table 4, entries 5 and 6) reveals that the addition reaction does not proceed completely stereospecifically. Small amounts of the wrong diastereomer can be detected, which is believed to arise from the triplet spin state of the carbene. Insertion into allylic C-H bonds occurs in the case of di- or trisubstituted alkenes (Table 4, entries 4-7). 

In accordance with this substitution rule, 10,12,14 and 16 were cyclopropanated well with diazomethane/Pd(OAc)2, while various trisubstituted steroidal ketones are not suitable substrates (Scheme 2). ... 

R=R =Ph, C02Me R-CMCj, Ph Rl=Me, H) and R2C=CH (R2 Pr, Bu, hexyl) has been examined . a new synthesis of trisubstituted alkenes by the Pd(OAc)2/PPh3 catalysed arylation of mono- and di-substituted acetylenes is observed in the presence of formic acid and a tertiary amine . Cyclopropanation of olefins is catalysed by a number of complexes of late transition metals and the electronic effects of the metal provide the stereochemical and regiochemical control . 

Apart from routine applications to cyclopropane synthesis,the application of new catalysts to the decomposition of diazo-compounds has received considerable attention. The use of palladium acetate, originally reported in 1972 by Paulissen et o/., has been extended and applied to diazomethane and ethyl diazoacetate in the presence of aP-unsaturated carbonyl compounds. With a- and a-substituted aP-unsaturated ketones, stereospecific cis-addition occurs in excellent yields, but the catalyst proves to be ineffective with analogous trisubstituted olefins, as illustrated for the formation of (110) with diazomethane. The use of palladium chloride with the... 

The transformation of cyclopropanes into cyclopropenes by elimination procedures has led to the preparation of several 3- and 3,3-di-substituted l-chloro-2-phenylcyclopropenes. The application of the fluoride-ion-promoted elimination of trisubstituted silicon halide to cyclopropene synthesis provides a simple route to 1-bromo- and 1-chlorocyclopropenes (156 X = Br or Cl) in high yield.Two... 

The obvious first test of methylene-bis(oxazolines) 6 was the copper-catalyzed cyclopropanation. Among the various derivatives that we had prepared (6 R = benzyl, c-alkyl, phenyl, tert-hutyl the bulky t rt-butyl-substituted derivative proved to be the most effective ligand, giving similarly high enantiomeric excesses as the semicorrin Ic (R = CMe20H) (Scheme 14) [25]. The same results were obtained by Masamune and coworkers in an independent parallel study [28]. More recently, Lowenthal and Masamune showed that the method works also well for certain trisubstituted and unsymmetrically disubstituted cis-olefins if the di-t rt-butyl-substituted ligand is replaced by structurally modified bis(oxazolines) [32]. 

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