Cyclopropanation, intramolecular

Carbenoid sources other than those derived from diazo precursors for catalytic cyclopropanation reactions are currently limited. Inter- and intramolecular catalytic cyclopropanation using iodonium ylide have been reported. Simple olefins react with iodonium ylides of the type shown in equations 83 and 84, catalysed by copper catalysts, to give cyclopropane adducts in moderate yield127 128. In contrast to the intermolecular cyclopropanation, intramolecular cyclopropanation using iodonium ylides affords high yields of products (equations 85 and 86). The key intermediate 88 for the 3,5-cyclovitamin D ring A synthon 89 was prepared in 80% yield as a diastereomeric mixture (70 30) via intramolecular cyclopropanation from iodonium ylide 87 (equation 87)1 0. 

Carbene)iron complexes are often only labile intermediates that undergo followup reactions as usually observed in carbene chemistry such as C-H insertion or cyclopropanation. Intramolecular C-H insertion reaction of (rj -cyclopentadienyl)-dicarbonyliron-carbene complexes provides bicyclic cyclopentanes (Scheme 4-60). The reaction has been applied for the synthesis of the fungal metabolite ( )-sterpurene and ( )-pentalenene. ... 

Nucleophilic attack of a 7i-allyl palladium complex gave cyclopropanes. Intramolecular cyclopropanahon was achieved... 

Meagher J F, Chao K J, Barker J R and Rabinovitch B S 1974 Intramolecular vibrational energy relaxation. Decomposition of a series of chemically activated fluoroalkyl cyclopropanes J. Phys. Chem. 78 2535 3... 

If a bromomethyl- or vinyl-substituted cyclopropane carbon atom bears a hydroxy group, the homoallyiic rearrangement leads preferentially to cyclobutanone derivatives (J. Sa-laun, 1974). Addition of amines to cydopropanone (N. J. Turro, 1966) yields S-lactams after successive treatment with tert-butyl hypochlorite and silver(I) salts (H.H. Wasserman, 1975). For intramolecular cyclopropane formation see section 1.16. 

Some straightforward, efficient cyclopentanellation procedures were developed recently. Addition of a malonic ester anion to a cyclopropane-1,1-dicarboxylic ester followed by a Dieckmann condensation (S. Danishefsky, 1974) or addition of iJ-ketoester anions to a (l-phenylthiocyclopropyl)phosphonium cation followed by intramolecular Wittig reaction (J.P, Marino. 1975) produced cyclopentanones. Another procedure starts with a (2 + 21-cycloaddition of dichloroketene to alkenes followed by regioselective ring expansion with diazomethane. The resulting 2,2-dichlorocyclopentanones can be converted to a large variety of cyclopentane derivatives (A.E. Greene. 1979 J.-P. Deprds, 1980). 

As final examples, the intramolecular cyclopropane formation from cycloolefins with diazo groups (S.D. Burke, 1979), intramolecular cyclobutane formation by photochemical cycloaddition (p. 78, 297f., section 4.9), and intramolecular Diels-Alder reactions (p. 153f, 335ff.) are mentioned. The application of these three cycloaddition reactions has led to an enormous variety of exotic polycycles (E.J. Corey, 1967A). 

Intramolecular Friedel-Crafts acylations of olefins also give cycHc a,P-unsaturated cycHc ketones. Cyclopropane fused bicyclo[5.3.0]octenones, thus obtained, were used in the preparation of the marine sesquiterpenes, africanol [53823-07-7] and dactjlol [58542-75-9] (174). 

Hodgson very recently reported an efficient intramolecular and completely dia-stereoselective cyclopropanation of bisliomoallylic and trisliomoallylic epoxides based on the use of a-lithiated epoxides. In a seminal paper, Crandall and Lin had reported that the reaction between t-BuLi and l,2-epoxyhex-5-ene (100) gave, inter alia, small amounts oftrans-bicyclo[3.1.0]hexan-2-ol (102, 9%) (Eq. a, Scheme 8.28)... 

Scheme 8.28 Base-promoted intramolecular cyclopropanation of unsaturated terminal epoxides.

Finally, an ingenious synthetic sequence by Trost, Cossy and Burks201 includes a unique desulphonylation reaction that involves an electron-transfer process. The synthetic sequence uses 1, l-bis(phenylsulphonyl)cyclopropane as a source of three carbon atoms, since this species is readily alkylated even by weakly nucleophilic species. Given an appropriate structure for the nucleophile, Trost found that desulphonylation with lithium phenanthrenide in an aprotic solvent allowed for an efficient intramolecular trapping of the resultant carbanion (equation 88). This desulphonylation process occurs under very mild conditions and in high yields it will undoubtedly attract further interest. 

Although the intramolecular cyclopropanation of simple alkenes easily occurs in those cases where a five- or six-membered ring is formed in addition to the three-membered ring [13], the intermolecular version of this process was described by Barluenga et al. in 1997 [ 14c]. Thus, this reaction has shown a high... 

Non-heteroatom-stabilised Fischer carbene complexes also react with alkenes to give mixtures of olefin metathesis products and cyclopropane derivatives which are frequently the minor reaction products [19]. Furthermore, non-heteroatom-stabilised vinylcarbene complexes, generated in situ by reaction of an alkoxy- or aminocarbene complex with an alkyne, are able to react with different types of alkenes in an intramolecular or intermolecular process to produce bicyclic compounds containing a cyclopropane ring [20]. 

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). 

Alkoxycarbene complexes with unsaturation in the alkyl side chain rather than the alkoxy chain underwent similar intramolecular photoreactions (Eqs. 10 and 11) [60]. Cyclopropyl carbene complexes underwent a facile vinyl-cyclopropane rearrangement, presumably from the metal-bound ketene intermediate (Eqs. 12 and 13) [61]. A cycloheptatriene carbene complex underwent a related [6+2] cycloaddition (Eq. 14) [62]. 

These reactions serve as a link in understanding selectivity differences between inter- and intramolecular cyclopropanation reactions, and they have been useful in defining the mechanism of addition as a function of catalyst [50,69,70]. 

Addition to a carbon-carbon triple bond is even more facile than addition to a carbon-carbon double bond, and there are now several reports of intermolec-ular [71] and intramolecular reactions [72-74] that produce stable cyclopropene products with moderate to high enantioselectivities. One of the most revealing examples is that shown in Scheme 9 [72] where the allylic cyclopropanation product (30) is formed by the less reactive Rh2(MEPY)4 catalyst, but macrocy-clization is favored by the more reactive Rh2(TBSP)4 and Rh2(IBAZ)4 catalysts and, as expected, the highest enantioselectivities are derived from the use of chiral dirhodium(II) carboxamidate catalysts. 

When free radicals are added to 1,5- or 1,6-dienes, the initially formed radical (9) can add intramolecularly to the other bond, leading to a cyclic product (10). When the radical is generated from an precursor that gives vinyl radical 11, however, cyclization leads to 12, which is in equilibrium with cyclopropylcarbinyl radical 13 via a 5-exo-trig reaction. A 6-endo-trig reaction leads to 14, but unless there are perturbing substituent effects, however, cyclopropanation should be the major process. 

The synthesis of different substituted finans by cyclization of 4-pentynones using potassium tert-butoxide in DMF was reported <96TL3387>. Dihydrofuran 32 can be prepared by a destannylative acylation of l-[(2-methoxyethoxy)methoxy]-2-(phenylsulfonyl)-2-(tributylstannyl)-cyclopropane. Treatment of 32 with BFj-EtjO yields 3-acyUurans via an intramolecular Prins-type reaction of the resulting oxonium ion intermediate <96TL4585>. 

Scheme 24 Titanium-mediated intramolecular reductive cyclopropanation of N-aUyl-a-amino acid dimethylamides...

Muller et al. have also examined the enantioselectivity and the stereochemical course of copper-catalyzed intramolecular CH insertions of phenyl-iodonium ylides [34]. The decomposition of diazo compounds in the presence of transition metals leads to typical reactions for metal-carbenoid intermediates, such as cyclopropanations, insertions into X - H bonds, and formation of ylides with heteroatoms that have available lone pairs. Since diazo compounds are potentially explosive, toxic, and carcinogenic, the number of industrial applications is limited. Phenyliodonium ylides are potential substitutes for diazo compounds in metal-carbenoid reactions. Their photochemical, thermal, and transition-metal-catalyzed decompositions exhibit some similarities to those of diazo compounds. 

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