Highly substituted cyclopentene

Jahn combined the formation of the enolate 2-713 resulting from an intermolecu-lar Michael addition of 2-711 and 2-712 with a radical reaction (Scheme 2.157) [363]. The enolate 2-713 did not undergo any further transformations due to the lack of appropriate functionalities. However, after formation of a radical using a mixture of ferrocenium hexafluorophosphate (2-714) and TEMPO, a new reaction channel was opened which afforded the highly substituted cyclopentene 2-715a diastereoselec-tively. 

Davies and coworkers developed a Et2AlCl-promoted stereoselective rearrangement of donor-acceptor VCPs VI, which were synthesized by the Rh2(Oct)4-catalyzed cyclopropanation of ethyl vinyl ethers IV, using vinyldiazoesters V tScheme 11.111. This process led to highly substituted cyclopentenes in good to excellent yields. 

Allyl cations generated from 2-alkyl allylic chlorides, e.g. (48), and zinc chloride react with substituted olefins to give good yields of highly substituted cyclopentenes, e.g. (49). Where unsymmetrical substrates lead to more than one cyclopentene the thermodynamically most stable isomer predominates. 

The carbene obtained by heating compound 68 with DMAD at first gave a cyclopropene derivative, which underwent further transformations (z/rro-substitution and cyclization) to afford tricyclic product 69 in 40% yield <1999TL1483>. The thermolysis carried out in the presence of ArCH=C(CN)2 and DMAD used in excess led to the formation of highly functionalized cyclopentene derivatives 70 <2003TL5029, 2005TL201>. 

A regioselective [3 + 2]-cycloaddition approach to substituted 5-membered carbo-cycles was made available by the use of allenylsilanes [188]. The reaction involves regioselective attack of an unsaturated ketone by (trimethylsilyl)allene at the 3-position. The resulting vinyl cation undergoes a 1,2-silyl migration. The isomeric vinyl cation is intercepted intramolecularly by the titanium enolate to produce a highly substituted (trimethylsilyl)cyclopentene derivative. 

Several examples of ring-closing metathesis indicate the highly selective nature of this reaction.161,162,224-226 The application of various Mo and Ru carbene catalysts allow formation of five-, six-, and seven-membered mono- and bicyclic rings. Formation of substituted cyclopentenes, for example, was shown... 

SCS-MP2 and the new perturbative B2-PLYP density functional methods provide accurate reaction barriers and outperform MP2 and B3-LYP methods when applied to the 1,3-dipolar cycloaddition reactions of ethylene and acetylene.39 Phosphepine has been shown to catalyse the asymmetric 3 + 2-cycloaddition of allenes with a variety of enones (e.g. chalcones) to produce highly functionalized cyclopentenes with good enantiomeric excess.40 The AuPPh3SbF6 complex catalysed the intramolecular 3 + 2- cycloaddition of unactivated arenyne- (or enyne)-yne functionalities under ambient conditions.41 A review of the use of Rh(I)-catalysed 3 + 2-cycloadditions of diaryl-and arylalkyl-cyclopropenones and aryl-, heteroaryl-, and dialkyl-substituted alkynes to synthesise cyclopentadienones for use in the synthesis of natural products, polymers, dendrimers, and antigen-presenting scaffolds has been presented.42... 

A similar intermolecular cyclization was recently utilized in the synthesis of highly substituted dihydropyrrole derivatives [133 -135]. In a specific example, the addition of pentadienyltosylamide derivatives 177 to propynyl(phenyl)iodo-nium triflate initiates a sequence of transformations that furnishes the complex, highly functionalized cyclopentene-annelated dihydropyrrole products 178 in moderate yields with complete stereoselection (Scheme 66). Under similar reaction conditions, the isomeric isoprene-derived tosylamide 179 reacts with propynyl(phenyl)iodonium triflate to give azabicyclo[3.1.0]hexane 180 as the final product [134]. 

The reaction is carried out in benzene at 60 °C over a period of 14 hours, using the various components in a mole ratio of dibromo ketone, olefin/ Fe2(CO)9 1 4 1.2. The simple diastereose-lectivity of the cycloaddition has been found to be rather moderate, with mixtures of cis- and Oau.T-products observed. An extension of this procedure involves addition to the C—C double bond of enamines5. Following elimination of the appropriate amine, the procedure provides an efficient route to substituted cyclopentenes, in some cases with very high tram selectivity. 

Allenylsilanes combine with electron-deficient alkenes or alkynes regio- and stereo-selectively to afford highly substituted and functionalized cyclopentenes (Scheme 10). The [3 + 2] annulation reaction has been used for heteroannulation approaches to five-membered oxygen and nitrogen heterocycles.15,16 One particularly useful application of the method is that readily available tropylium salts can function as allenophiles in a general [3 + 2] annulation route to substituted azulenes (equation 3).17... 

Mikami [9] successfully utilized the Cu-phosphoramidite complex derived from chiral Bgand 8 and Cu(OTf)2 for the desymmetrization of cyclopentene-l,3-dione 9 (Scheme 11.3). The resulting enolates generated with dimethylzinc were efficiently trapped with butylaldehyde. Highly substituted cyclopentanedione 10 was formed with excellent diastereoselectivities and enantiomeric purities. This domino process was used for the formal synthesis of (+)-madindoline B (12) [10]. 

Davies s group also extended this methodology toward the asymmetric syntheses of substituted cyclopentenes. Although chiral monocyclic VCPs isomerized to racemic cyclopentenes under the reaction conditions, the use of fused chiral VCPs led to the products in high yields with excellent enantioselectivity f Scheme 11.14T ... 

Deuterium labelling studies have revealed that the lithium amide-induced desym-metrizing rearrangements of 4-substituted cyclopentene oxides to cyclopentenols generally proceed by a -elimination mechanism. Highly enantioselective syntheses of 4-substituted c -4-hydroxymethylcyclopent-2-en-l-ols are described. 

The [3+2] annulation reaction of a-substituted allenoates with ester-activated a,p-unsaturated imines in the presence of MePPh2 leads to the synthesis of highly functionalized cyclopentenes bearing an all-carbon quaternary center (Scheme 6.8) [10],... 

Palladium-catalyzed annulation reactions of conjugate acceptors and allenyl boronic ester provide substituted cyclopentenes in high yields and diastereose-lectivities (Scheme 6.24). These reactions are hypothesized to commence by the conjugate addition of a nucleophilic propargyl-palladium complex. Transmetalation of allenylboronic acid pinacol ester with a Pd(II) catalyst proceeds via an SE2 mechanism to provide the propargyl-palladium complex, which on conjugate attack on the electrophile furnishes an allene intermediate. Finally, endo carbopalladation of the pendant allene and protodepalladation generates the cyclopentene [28]. 

The first models for asymmetric induction in [2 + 2] cycloadditions are ketimines derived from precursors such as (25), which react with both cyclic and acyclic alkenes to give adducts with high enantiomeric excesses. Full details have been reported on the regio- and stereo-specificity of the addition of dichloroketene to 1-substituted cyclohexenes. Methyl (phenylthiomethyl)-ketene (26) provides a further example of a ketene which, after cycloaddition to cyclopentadiene, undergoes facile opening of the cyclobutane that is thus formed to provide vicinally substituted cyclopentene derivatives. ... 

Beginning in 1998, Ma has developed a series of cascade cross-coupling cycliza-tion reactions of functionalized allenes with organic hahde in the presence of palladium species, leading to various highly substituted carbocycles or heterocycles, such as y-butenolides, y-lactams, y-iminolactones, vinylic epoxides, 2,5-dihydrofurans, 2,3-dihydropyrroles, furans, vinylic cyclopropanes, and cyclopentenes, which depend on the nature of the functional groups and the substituents on the allenes. This has been well summarized by the author [102] (Scheme 6.76). 

Furthermore, 12 was found to catalyze [3-+2] cycloaddition of allenes with various P-substituted a,P-unsaturated ketones to produce enantiomerically enriched, highly functionalized cyclopentenes possessing two contiguous stereocenters [41]. Along with this line, Marinetti reported that 2-aryl-l,l-dicyanoethylenes were also good reaction partners of the allenoates in the 12-catalyzed cycloaddition [42] (Scheme 7.24). 

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