Cyclopropanation carbocycle synthesis

Miscellaneous Iminium Catalyzed Transformations The enantioselective construction of three-membered hetero- or carbocyclic ring systems is an important objective for practitioners of chemical synthesis in academic and industrial settings. To date, important advances have been made in the iminium activation realm, which enable asymmetric entry to a-formyl cyclopropanes and epoxides. In terms of cyclopropane synthesis, a new class of iminium catalyst has been introduced, providing the enantioselective stepwise [2 + 1] union of sulfonium ylides and ot,p-unsaturated aldehydes.As shown in Scheme 11.6a, the zwitterionic hydro-indoline-derived catalyst (19) enables both iminium geometry control and directed electrostatic activation of sulfonium ylides in proximity to the incipient iminium reaction partner. This combination of geometric and stereoelectronic effects has been proposed as being essential for enantio- and diastereocontrol in forming two of the three cyclopropyl bonds. 

Hudlicky T, Reed JW (1991) Rearrangements of vinyl cyclopropane and related systems. In Trost BM (ed) Comprehensive organic synthesis, vol 5. Pergamon Press, Oxford, p 899 Hudlicky T, Becker DA, Fan RL, Kozhushkov S (1997) Carbocyclic three-and four-member-ed ring compounds. In de Meijere A (ed) Houben-Weyl methods of organic chemistry, vol El7c. Thieme, Stuttgart, p 2538... 

Where the diene function is attached to or is part of a carbocyclic system, the vinyl cyclopropane formation and subsequent rearrangement affords a reliable approach to the formation of tricyclic carbocycles. Some of the most elegant demonstrations of the use of this methodology in total synthesis of fused cyclopentanoid terpenes come from the work of Hudlicky and coworkers (equations 63-66)90 95"100. In these cases the diazoketones bear a carboxylate-substituted double bond of diene and the intramolecular cyclopropanation requires the combination of CuS04/Cu(acac)2 as catalyst. 

A method for the synthesis of eight-membered carbocycles based on a new tandem tungsten-catalysed cycloisomerization-cyclopropanation reaction has been reported (Scheme 99).143 This is a catalytic reaction in which a heteroatom-stabilized Fischer... 

Reactions of cyclopropane derivatives activated by one type of functional group have been well understood and applied in organic synthesis for quite some time1). The far-reaching analogy between reactivity of olefins and cyclopropanes can be explained by the tc-type orbitals of strained three membered carbocycles and their interaction with the activating substituents 2,3>. 

The most important discoveries in ruthenium catalysis are highlighted and innovative activation processes, some of which are still controversial, are presented in this volume. They illustrate the usefulness in organic synthesis of specific reactions including carbocyclization, cyclopropanation, olefin metathesis, carbonylation, oxidation, transformation of silicon containing substrates, and show novel reactions operating via vinylidene intermediates, radical processes, inert bonds activation as well as catalysis in water. 

The synthesis of cyclopropanes from carbonyl compounds represents a new approach for converting zirconacycles into carbocycles via a deoxygenative ring contraction under Lewis acid activation. It differs in that from the spontaneous Kulinkovich process. Further progress would involve extension to the synthesis of 1,2-substituted cyclopropanes and the development of catalytic and enantioselective variants. 

Reductive dehalogenation is an efficient method of synthesis of cyclopropanes spiroannulated to five- and higher-membered carbocycles (i.e. compounds in which spiroannulation does not result in accumulation of extra strain) . The required gem-(dihalomethyl)cycloalkanes are usually prepared by halogenation of the precursor diols (equation 1). The cyclization is most efficiently accomplished in the Zn-alcohol-water system . For example, spiro[2.5]octane 7 was prepared in 91% yield using this procedure. This method is useful even for a one-step preparation of bis-spirocyclopropyl compounds as exemplified in equation 2. However, the application of the reductive dehalogenation method to the synthesis of more strained SPC (i.e. spirohexane or spiropentane) often leads to rearranged products. For example, methylenecyclopentane was the only product obtained from bis(bromomethyl)cyclobutane (equation 3) ... 

Chiral bicyclic lactams are excellent precursors to a wide variety of chiral, non-racemic carbocycles including cyclopentenones, cyclohexenones, cyclopropanes, indanones, naphthalenones, and asymmetric keto acids.3 Recently they have been applied to the synthesis of chiral, non-racemic pyrrolidines and pyrroiidinones,4 that are medicinally and synthetically important molecules.5 The three-step procedure described here provides an efficient route (overall yield 46%) to (S)-5-heptyl-2-pyrrolidinone of high enantiomeric purity. The scheme below illustrates this reaction. 

Bao XM, Katz S, Pollard M, Ohlrogge J. Carbocyclic fatty acids in plants biochemical and molecular genetic characterization of cyclopropane fatty acid synthesis of Sterculia foetida. Proc. Natl. Acad. Sci. U.S.A. 2002 99 7171-7177. 

This intramolecular carbolithiation of silylated conjugated enynes was then successfully applied to the construction of small carbocycles such as cyclopropanes and cyclobutanes [35]. Due to the stabilization of the propargylic organolithium after carbocyclization, the reversibility of the intramolecular carbometallation of strained carbocycles was impeded (Scheme 7-37), e.g., for the cyclobutane synthesis. 

The transient zirconocene butene complex, 105, has proved to be useful in a number of organic transformations. For example, butene substitution of zirconocene alkene complexes with alkoxy-substituted olefins results in /3-alkoxide elimination to furnish the zirconocene alkoxy compounds (R = Me, 123 R = Bnz, 124) (Scheme 16).50,51 Addition of propargyl alcohols to the zirconocene butene complex, 105, affords homoallylic alcohols. These reactions are of limited utility owing to the lack of stereoselectivity or formation of multiple products. Positioning the alkoxide functional group further down the hydrocarbyl chain allows synthesis of cyclopropanes, though mixtures of the carbocycle and alkene products are obtained in some cases (Scheme 16).52... 

The synthesis of carbocyclic compounds from acyclic precursors can be accomplished by a sequence of radical reactions, where thiyl radicals act as catalysts. As an example, the generation of homoallyl radicals through the addition of phenyl-thiyl radical to the double bonds of vinyl cyclopropanes results in the multi-step synthesis of cyclopentanoids [62]. The mechanism is shown in Scheme 13. Feldman and coworkers have demonstrated that the success of this strategy is based on the coupling of vinyl cyclopropanes with the electronically complementary functionalized alkenes. A judicious choice of substituents R and X accelerates the rate limiting step (c). 

Cyclopenten-l-ol, l,3-dimethyl-2-(7-methyl-3,7-tridecadien-ll-ynyl), , )-, 91-92, 279-280 2-Cyclopenten-1 -one, 3-methyl-2-(2-pentenyl)-, (Z)- (fasmone) synthesis, 29 2-Cyclopenten-l-ones syntheses by cyclizations from 1,4-dioxo compounds, 69, 79 from 5-nitro-l,3-diones, 81 Cyclophanes of porphyrins, 253 meta-Cyclophanes, 38, 338 pora-Cyciophanes = tricyclo[8.2.2.24,7]hexadeca-4,6,10,12,13,15-hexaenes synth., 38-39 Cyclopropane derivs. See Carbocycles, 3-membered... 

The synthesis of carbocycles via a two-component cascade reaction in an asymmetric fashion has attracted much attention from the chemical community. Due to his importance in natural products, the synthesis of cyclopropanes, cyclopentanes, and cyclohexanes has been one of the common goals for organocatalytic methodologies. The high stereoselectivity achieved, green procedures, and soft conditions make this organocatalytic approximation one of the most attractive ones to build complex cyclic scaffolds. 

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