Cyclopropanes syntheses with -

FREUNO-GUSTAVSON Cyclopropane Synthesis Cyclopropane synthesis from 1,3-dihaloalkenes with metals... 

H. E. Simmons and R. D. Smith of the DuPont Company had developed a useful cyclopropane synthesis by reacting a zinc-copper couple with an alkene. 

The increasingly common theme of developing new pyrrole syntheses that involve cyclopropane fragmentations appeared in a type Ilae pyrrole synthesis <06OL835>. Treatment of doubly activated cyclopropane 43 with benzylamine in the presence of magnesium sulfate led to complex pyrrole 44 via a nucleophilic cleavage of the cyclopropane ring, intramolecular condensation, and isomerization of the exocyclic JC-bond. 

Doyle, M. P. McKervey, M. A. Ye, T. Modem Catalytic Methods for Organic Synthesis with Diazo Compounds From Cyclopropanes to Yelides ... 

An alternative cyclopropane synthesis via an active methylene compound can also be enhanced by sonication [110]. The number of examples quoted in the literature is low but in the case of ethyl cyanoacetate and dibromoethane sonicated with potassium carbonate and polyethylene glycol in ethylene dichloride the expected cyclopropane is generated in 85 % yield (Eq. 3.19). 

Wade and co-workers used a similar strategy for the synthesis of fran5-l,2-dinitrospiro-pentane (10), which is prepared in 43 % yield by treating the dianion of l,l-few(nitromethyl)-cyclopropane (9) with iodine in DMSO the latter prepared by treating the corresponding diamine (8) with excess ozone while absorbed onto the surface of silica gel. 

The reaction of vinylcarbenoids with vinyl ethers can lead to other types of [3 + 2] cycloadditions. The symmetric synthesis of 2,3-dihydrofurans is readily achieved by reaction of rhodium-stabilized vinylcarbenoids with vinyl ethers (Scheme 14.17) [107]. In this case, (J )-pantolactone is used as a chiral auxihary. The initial cyclopropanation proceeds with high asymmetric induction upon deprotection of the silyl enol ether 146, ring expansion occurs to furnish the dihydrofuran 147, with no significant epi-merization during the ring-expansion process. 

The remarkably efficient cyclopropanation reaction with an in-situ-generated zinc carbenoid, Eq. (61) provided a straightforward synthesis of the monoterpene sabinene (42) starting from the P-keto ester 41 [58],... 

Like their sulfur counterparts (Section 3.2.4.4.2.), 1 -lithiocyclopropyl selenides 1, as generated by reductive lithiation of bis(selanyl)cyclopropanes 173 with butyllithium in diethyl ether or tetrahydrofuran, react with aldehydes or ketones to give /Lhydroxy selenides 2, which rearrange to cyclobutanones 3 on treatment with p-toluenesulfonic acid in wet benzene.174 175 The method was used in a total synthesis of a-cuparenone.175... 

These complexes can be isolated in some cases in others they are generated in situ from appropriate precursers, of which diazo compounds are among the most important. These compounds, including CH2N2 and others, react with metals or metal salts (copper, palladium, and rhodium are most commonly used) to give the carbene complexes that add CRR to double bonds.1063 Optically active complexes have been used for enantioselective cyclopropane synthesis.1064... 

An asymmetric cyclopropane synthesis has been achieved by the addition-cyclization reaction of a chiral a,/ -unsaturated sulfoxide with a Grignard reagent (equation 32)49. 

KISHNEK CYCLOPROPANE SYNTHESIS. Formation of cyclopropane derivatives by deeompoxiiion of pyra/olines formed by reacting tr/l-unsiiiurated kelones or aldehydes with hydrazine. 

Doyle MP, McKervey MA, Ye T (1998) In Modern catalytic methods for organic synthesis with diazo compounds from cyclopropanes to ylides. Wiley, New York... 

Let us take a look at the back cover of Cram and Hammond s Textbook of organic chemistry, where a number of dream molecules are depicted. Truncated tetra-hedrane, or heptacyclo[5.5.0.02 12.03 5.041. 06 8.0911]dodecane, C12Hi2 (2) appears to offer a possibility of its cyclopropane bonds with high p-character to interact over the surface of the molecule. Structure 2 has eight faces and is formally obtained by truncating four vertices of tetrahedron (3) it is also the target of synthesis by several research groups (Woodward 1970). 

An exceptional case of ring formation and cleavage deals with a system incorporating two cyclopropane units with donor-acceptor pattern. Photochemical synthesis of 94 and electrocyclic reaction afford the unusual bridged hexanooxepin 9554). 

An attempted synthesis of dithioesters 220 by stepwise treatment of enolates from cyclopropanes 97 with carbon disulfide and methyl iodide lead to an unexpected new product without a cyclopropane ring. By spectroscopic means and study of the reactions dihydrothiophene structure 222 has been established 98). 

Different allyl 2-lithioaryl ethers underwent a tandem carbolithiathion/y-elimination in Et20/TMEDA, affording o-cyclopropylphenol derivatives in a diastereoselective manner. The use of (-)-sparteine as a chiral ligand instead of TMEDA allowed the synthesis of cyclopropane derivatives with up to 81% ee. The following scheme illustrates this stereoselective process for the formation of chiral o-cyclopropylphenols <02OL2225>. 

The synthetic potential of organozirconocenes is greatly expanded by their easy transformation into other organometallics. Therefore, transmetalation-based approaches to cyclopropane synthesis have been reported. The reaction of zirconacyclopentene with phthaloyl chloride in the presence of CuCl was used for the preparation of cyclopropylenolate derivatives in moderate yields (Scheme 29) [39]. 

Treatment of diethyl malonate and related compounds with 1,2-dihaloethane in the presence of base constitutes a classical method of cyclopropane synthesis. The reaction can be conveniently carried out under PTC conditions. An improved method utilizing solid-liquid phase transfer catalysis has been reported The reaction of dimethyl or diethyl malonate with 1,2-dibromoalkanes except for 1,2-dibromethane tends to give only low yields of 2-alkylcyclopropane-l, 1-dicarboxylic esters. By the use of di-/ r/-butyl malonate, their preparations in satisfactory yields are realized (equation 134). The 2-alkylcyclopropane derivatives are also obtained from the reaction of dimethyl malonate and cyclic sulfates derived from alkane-1,2-diols (equation 135) Asynunetric synthesis... 

Intermolecular cyclopropanation reactions with ethyl diazoacetate have been employed for the construction of the cyclopropane-containing amino acid 7 (equation 25) Thus, rhodium(II) acetate catalysed decomposition of ethyl diazoacetate in the presence of d-cbz-vinylglycine methyl ester 5 afforded cyclopropyl ester 6 in 85% yield. Removal of the protecting group completed the synthesis of 7. Another example illustrating intermolecular cyclopropanation can be found in Piers and Moss synthesis of ( )-quadrone 8" (equation 26). Intermolecular cyclopropanation of enamide or vinyl ether functions using ethyl diazoacetate has also been used in the synthesis of eburnamonine 9", pentalenolactone E ester 10" and ( )-dicranenone A11" (equations 27-29). 

Liu et al. reported in 2003 on the synthesis and cytotoxicities of 3 -cyclopropane analogs with both Tot- and 7(3-OH and 2 R)- and 2 (5)-OH functionalities. Both 2 - R) isomers were 400 times less active than paclitaxel in A2780 cancer cell assays, and 2 -(5) isomers displayed even weaker cytotoxicities. Unsatisfactory results may have developed from small volumes of the 3 -cycloprapane, which is similar to 3 -methyl in 9(R)-dihydro paclitaxels as reported earlier. As mentioned, larger groups such as isobutyl or isobutenyl may interact with the receptor better. 

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