Cyclopropanes functionalised

J-Oxygen-functionalised sp3 organolithium compounds react with alkenyl-carbene complexes to generate the corresponding cyclic carbene complexes in a formal [3+3] process (see Sect. 2.8.1). In those cases where the organolithium derivative contains a double bond in an appropriate position, tricyclic ether derivatives are the only products isolated. These compounds derive from an intramolecular cyclopropanation of the corresponding cyclic carbene complex intermediate [89] (Scheme 83). 

In recent years, the variety of useful diazo substrates for asymmetric intramolecular cyclopropanation processes has really expanded. As another example, Charette and Wurz have reported the first example of an intramolecular cyclopropanation involving a-nitro-a-diazo carbonyl compounds.This reaction, catalysed by Rh2[(S)-DOSP]4, led to the formation of nine-membered nitrocyclopropyl lactones in good yields and enantioselectivities with extremely high diastereoselectivities (Scheme 6.17). This novel methodology constituted an efficient entry into chiral functionalised macrocyclic-fused cyclopropane oc-amino acids. 

Functionalised cyclopropanes can be prepared from 1,2-dioxines by reaction with stabilised phosphorus ylides . 

More recent reports from Cordova [155] and Wang [156] have described the cyclopropanation of a, P-unsaturated aldehydes 99 with diethyl bromomalonates 100 and 2-bromo ethyl acetoacetate catalysed by a series of diaryIprolinol derivatives. Both describe 30 as being the most efficient catalyst in many cases and optimal reaction conditions are similar. Some representative examples of this cyclopropanation are shown in Scheme 40. The transformation results in the formation of two new C-C bonds, a new quaternary carbon centre and a densely functionalised product ripe for further synthetic manipulation. Triethylamine or 2,6-lutidine are required as a stoichiometric additive in order to remove the HBr produced during the reaction sequence. The use of sodium acetate (4.0 equivalents) as an additive led to subsequent stereoselective ring opening of the cyclopropane to give a,P-unsaturated aldehydes 101. It can be envisioned that these highly functionalised materials may prove useful substrates in a variety of imin-ium ion or metal catalysed transformations. 

An Australian worker has described recently a novel synthesis of highly functionalised cyclopropanes which proceeds in moderate yield, and is illustrated by the following example. Addition of the 2//-pyran-5-carboxylate 1 to the arsonium ylide 2 in THF at 0°C gave two trans-diastereomers 3 in 64% yield. 

Preparation of mono-adducts of fullerene - for studies on electrostatic interactions - was undertaken by cyclopropanation of fullerene with appropriately functionalised malonic esters 1 (Bingel reaction) to form 2. Coupling with the tert-butyl protected oligoamide-amino-dendron 3 and subsequent hydrolysis lead to the water-soluble fullerene dendron 5, which can carry up to nine negative charges after depro to nation. After association with the zinc complex of cytochrome C, photoinduced electron transfer (PET) from the redox protein to the fullerene can be accomplished, which was studied by fluorescence spectroscopy. 

Brunner et al. reported core-functionalised dendrimer metal catalysts ("dendri-zyme ) for use in enantioselective catalysis [lb, 10, 11]. Optically active dendrimer ligands were used, for example for the reaction of styrene with ethyl diazoacetate in a Cu(I)-catalysed enantioselective cyclopropanation. The starting compound for the preparation of these ligands was L-aspartic acid. However, (IS,2 S)-2-amino-1-phenyl-1,3-propanol can also serve as reactant for the synthesis of optically active dendrimer ligands. 

The violence of superbasic slurries towards functionalised organic molecules means that they are at their most effective with simple hydrocarbons they also tolerate ethers and fluoro substituents. LiCKOR will deprotonate allylic, 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 496 and 497.441 ( Li/K indicates metallation with a structurally ill-defined mixture of lithium and potassium.)... 

The important commercial compound (/ )-pantolactone is formed in high yield and ee from the bis-carbamate 417 after carboxylation and lactonisation.178 Attempts to quench the organolithium with Me3SiCl failed instead the silyl chloride acted as a Lewis acid, promoting displacement of the second carbamate and leading to the cyclopropane 420.162>179 Further functionalisation of the cyclopropane was possible by stereospecific alkylation of the ring. 

One of the attractions of dirhodium paddelwheel complexes is their ability to catalyse a wide variety of organic transformations such as C-H insertions, cyclopropanations and ylide formation. A review on the application of high symmetry chiral Rh2(II,II) paddlewheel compounds highlights their application as catalysts for asymmetric metal carbenoid and nitrenoid reactions, and as Lewis acids.59 Their impressive performance as catalysts in C-H functionalisation reactions has been exploited in the synthesis of complex natural products and pharmaceutical agents. A recent review on catalytic C-H functionalisation by metal carbenoid and nitrenoid insertion demonstrates the important role of dirhodium species in this field.60... 

An exciting recent development has been the discovery that titanocene-mediated reactions of oo-carbonyl epoxides [36] and o>alkenyl epoxides [37] can produce functionalised cyclopropane and cyclobutane derivatives. For example, Fernandez-Mateos and co-workers discovered that treatment of... 

Scheme 8 Zinc-mediated preparation of cyclopropanes from functionalised iodobutenes...

A detailed mechanistic study of the reaction between stabilised ylides (42) and 1,2-dioxines has been reported by Taylor and coworkers. This reaction provides a facile route to functionalised cyclopropanes (Scheme 12). The same group has also discovered that addition of chiral 3-ketoiminato (43) or cobalt salen (44) complexes, leads to a catalytic asymmetric ring-opening of me so 1,2-dioxines, affording enantio-enriched cis y-hydroxy enones that react with the stabilised ylides to give enantio-enriched cyclopropanes. ... 

Isolable cyclopropane-containing addncts can be obtained from V-Boc-pyrrole," and ozonolysis of the mono adduct is a means for the synthesis of heavily functionalised cyclopropanes." ... 

There are also excellent total syntheses of spirotryprostatins which do not apply intermolecular functionalisation of the indole 3-position with a C5 prenyl-type precursor and are, therefore, not discussed in detail. Carreira and co-workers started from 3-diazo-2-oxindole, which was used in a Rh(I)-catalysed cyclopropanation of 1,3-pentadiene. The resulting cyclopropane was subjected to Mgl2-catalysed ring expansion and added to an imine affording the spiro[5.5] partial structure [130, 131]. Overman and Rosen built up the indole system by intramolecular Heck reaction of a functionalised iodoaniline [132,133]. In a model study building up the indole system, Cacchi and co-workers synthesised 3-prenylindoles via Pd-catalysed cyclisation of orf/io-alkynyltrifluoroacetanilides with prenyl esters [134]. 

Scheme 7.9 Asymmetric Michael initiated ring closure reactions of a-bromo mal-onates and electron-poor alkenes to functionalised cyclopropanes catalysed by diaryl prolinols.

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