Cycloadditions cyclopentene

In addition to the electronic effects of substituents, several other structural features affect the reactivity of dipolarophiles. Strain increases reactivity. Norbornene, for example, is consistently more reactive than cyclopentene in 1,3-dipolar cycloadditions. Cyclopentene is also more reactive than cyclohexene. Conjugating substituents, such as the phenyl group in styrene, usually increase reactivity of dipolarophiles (compare styrene with 1-alkenes in Table 10.3). 

The intramolecular [In + 2 rr] cycloaddition ofmethylenecyclopropane with the alkyne in 117 using isopropyl phosphite as a ligand affords the methylene-cyclopentene 118[55]. 

An interesting probe of reactivity was presented by Burton in his study of cycloadditions of l,2-disubstituted-3,3,4,4-tetrafluorocyclobutenes and 1,2-disub-stituted-3,3,4,4,5,5-hexaf1uorocyclopentenes with butadiene, 2-methylbutadiene, and 2,3-dimethylbutadiene [86], On the basis of the extent of their conversions to adducts, the relative reactivities of the cyclobutenes and of the cyclopentenes are as shown in equation 74. A typical reaction is shown in equation 75. 

The mechanism of the cycloaddition of phenyl azide to norbornene has been shown to involve a concerted mechanism with a charge imbalance in the transition state (199). In a similar manner the cycloaddition of phenyl azide to enamines apparently proceeds by a concerted mechanism (194, 194a). This is shown by a rather large negative entropy of activation (—36 entropy units for l-(N-morpholino)cyclopentene in benzene solvent at 25°C), indicative of a highly ordered transition state. Varying solvents from those of small dielectric constants to those of large dielectric constants has... 

Adducts derived from cyclopropyl-TMM reactions are versatile synthetic intermediates. Alkylidenecyclopropanes have been proven useful in further Pd-cata-lyzed transformations [4], On the other hand, vinylcyclopropanes can undergo smooth thermal ring-expansion to cyclopentenes. Thus, a total synthesis of 11-hy-droxyjasionone (27) was achieved with the cyclopropyl-TMM cycloaddition as the crucial step, and the thermal rearrangement of the initial adduct (28) as an entry to the bicyclo[6.3.0]undecyl compound (29), a key intermediate in the synthetic sequence (Scheme 2.9) [19]. 

The photochemical [2 + 2] cycloaddition of cyclopentene to pentaflu-oropyridine in cyclohexane gave a 1 1 adduct, which in excess olefin gave a single 1 2 adduct (37) (82JOC4462). The solvent has an important role, as in its absence two 1 2 adducts are obtained. With PhC CR in cyclohexane, the nature of R determined whether a triene (R = f-butyl) or tetraene (R = Me) was in the product mixture (89T1755). A mixture of 1 2 and two 1 1 adducts was obtained by [2 + 2] addition of but-2-yne in the absence of a solvent [87JFC(20)745]. 

In the same way as arylcarbene complexes, alkenylcarbene complexes typically react with alkynes to provide [3C+2S+1C0] Dotz cycloadducts (see Chap. ccChromium-Templated Benzannulation Reactions , p. 123 in this book). However, some isolated examples involving the formation of five-membered rings through [3C+2S] cycloaddition processes have been reported [71]. In this context, de Meijere et al. found that /J-donor-substituted alkenylcarbene complexes react with alkynes to give cyclopentene derivatives [71a]. This topic is also discussed in detail in Chap.ccThe Multifaceted Chemistry of Variously Substituted a,/J-Unsaturated Fischer Metalcarbenes , p. 21 of this book. 

Sect. 2.1.1) and [3C+2S] cyclopentene derivatives. The product distribution can be controlled by choosing the appropriate reaction conditions [72]. Moreover, the cyclopentene derivatives are the exclusive products from the coupling of fi-pyrrolyl-substituted carbene complexes [72b,c] (Scheme 25). The crucial intermediate chromacyclobutane is formed in an initial step by a [2+2] cycloaddition. This chromacyclobutane rearranges to give the rf-complex when non-coordinating solvents are used. Finally, a reductive elimination leads to the formal [3C+2S] cyclopentene derivatives. 

Coupling of alkenylcarbene complexes and siloxy-substituted 1,3-dienes affords vinylcyclopentene derivatives through a formal [3C+2S] cycloaddition process. This unusual reaction is explained by an initial [4C+2S] cycloaddition of the electron-poor chromadiene system as the 471 component and the terminal double bond of the siloxydiene as the dienophile. The chromacyclohexene intermediate evolves by a reductive elimination of the metal fragment to generate the [3C+2S] cyclopentene derivatives [73] (Scheme 26). 

The reaction of JV,iV-dimethylhydrazones (1-amino-1-azadienes) and alkenylcarbene complexes mainly produces [3C+2S] cyclopentene derivatives (see Sect. 2.6.4.5). However, a minor product in this reaction is a pyrrole derivative which can be considered as derived from a [4S+1C] cycloaddition process [75]. In this case, the reaction is initiated by the nucleophilic 1,2-addition of the nitrogen lone pair to the metal-carbon double bond followed by cyclisation and... 

At this point the catalytic process developed by Dotz et al. using diazoalkanes and electron-rich dienes in the presence of catalytic amounts of pentacar-bonyl(r]2-ds-cyclooctene)chromium should be mentioned. This reaction leads to cyclopentene derivatives in a process which can be considered as a formal [4S+1C] cycloaddition reaction. A Fischer-type non-heteroatom-stabilised chromium carbene complex has been observed as an intermediate in this reaction [23a]. 

Small amounts of cyclopentene derivatives are detected in cyclopropanation reactions of electron-deficient dienes, but they may result from thermal rearrangement of the corresponding vinyl cyclopropanes and not from a direct [4+1] cycloaddition... 

The presence of the catalyst can also favor multiple Diels-Alder reactions of cycloalkenones. Two typical examples are reported in Schemes 3.6 and 3.7. When (E)-l-methoxy-1,3-butadiene (14) interacted with 2-cyclohexenone in the presence of Yb(fod)3 catalyst, a multiple Diels-Alder reaction occurred [21] and afforded a 1 1.5 mixture of the two tricyclic ketones 15 and 16 (Scheme 3.6). The sequence of events leading to the products includes the elimination of methanol from the primary cycloadduct to afford a bicyclic dienone that underwent a second cycloaddition. Similarly, 4-acetoxy-2-cyclopenten-l-one (17) (Scheme 3.7) has been shown to behave as a conjunctive reagent for a one-pot multiple Diels-Alder reaction with a variety of dienes under AICI3 catalysis, providing a mild and convenient methodology to synthesize hydrofluorenones [22]. The role of the Lewis acid is crucial to facilitate the elimination of acetic acid from the cycloadducts. The results of the reaction of 17 with diene... 

Although 1-vinylnaphthalene thermally reacts with 4-acetoxy-2-cyclopenten-1-one (98) to regioselectively afford 99, the isomer 2-vinylnaphthalene gives the same thermal cycloaddition with low yield (30 %) and reacts satisfactorily only with 98 at 10 kbar (Scheme 5.10). Both products 99 and 101 were converted into the cyclopenta[a]phenanthren-15-one (100) and cyclopenta[c]phenanthren-l-one (102) isomers. Acetoxyketone 98 acts as a synthetic equivalent of cyclo-pentadienone (114 in Scheme 5.14) in cycloaddition reactions [33]. 

Utilizing an alternate mode of Diels-Alder reactivity, Harman has examined the cycloaddition reactions of 4,5-T -Os(II)pentaammine-3-vinylpyrrole complexes with suitably activated dienophiles <96JA7117>. For instance, cycloaddition of the p-vinylpyrrole complex 58 with 4-cyclopentene-l,3-dione, followed by DDQ oxidation affords 59, possessing the fused-ring indole skeleton of the marine cytotoxic agent, herbindole B. 

Tam and coworkers [311] developed a method for the synthesis of 1,3-disubsti-tuted cyclopentanes 6/4-124 and cyclopentenes. Thus, reaction of the condensed isoxazolines 6/4-123, easily obtainable by a 1,3-dipolar cycloaddition, gave 6/4-124 in good yields using Mo(CO)6 (Scheme 6/4.30). 

The introduction of heterodienes has extended the synthetic versatility of cycloaddition reactions in organic synthesis.150 Denmark and coworkers have developed the use of nitroalkenes as dienes in [4+2] cycloaddition. Nitroalkenes react with simple alkenes in the presence of SnCl4 as a promoter. For example, the reaction of nitrocyclohexene with cyclopentene gives three products. The major product is awh-isomer, which arises from an exo approach of cyclopentene toward nitrocyclohexene (see Eq. 8.94).151... 

The authors chose pyruvic acid as their model compound this C3 molecule plays a central role in the metabolism of living cells. It was recently synthesized for the first time under hydrothermal conditions (Cody et al., 2000). Hazen and Deamer carried out their experiments at pressures and temperatures similar to those in hydrothermal systems (but not chosen to simulate such systems). The non-enzymatic reactions, which took place in relatively concentrated aqueous solutions, were intended to identify the subsequent self-selection and self-organisation potential of prebiotic molecular species. A considerable series of complex organic molecules was tentatively identified, such as methoxy- or methyl-substituted methyl benzoates or 2, 3, 4-trimethyl-2-cyclopenten-l-one, to name only a few. In particular, polymerisation products of pyruvic acid, and products of consecutive reactions such as decarboxylation and cycloaddition, were observed the expected tar fraction was not found, but water-soluble components were found as well as a chloroform-soluble fraction. The latter showed similarities to chloroform-soluble compounds from the Murchison carbonaceous chondrite (Hazen and Deamer, 2007). 

The photoindueed 1,7-cycloaddition of carbon monoxide across the divinyl-cyclopropane derivative 32 yields the two cyclic dienyl ketones 34, via the ferracyclononadiene intermediate 33 [18]. (Scheme 11) cyclopentene rearrangement. The dienylcyclopropane 35 is capable of forming the complex 36, followed by ring enlargement to 37 [19]. 1,1-Dicyclopropylethylene 29 is also converted to the 1-cyclopropyl-1-cyclopentene 38. The additional functionality of vinylcyclopropanes is necessary to serve as a 7t-donor... 

Highly alkylated l-chloro-2-(trimethylsilyl)cyclopentenes 44, which are of interest as possible cyclopentyne precursors, were prepared by reacting 3-chloro-3-methyl-l-(trimethylsilyl)but-l-yne (45) with 1,1-dialkylated or 1,1,2-trialkylated ethylenes in the presence of titanium tetrachloride35. Because of the low S/v 1 reactivity of 45, the yields of the products were moderate. The stepwise [3 + 2]-cycloaddition mechanism discussed above was proven by the isolation of the intermediate acyclic adduct (in 74% yield) when 45 and isobutene were reacted in the presence of BCI3. Under these conditions, the intermediate 46 could be trapped by Cl since BCI4 is more nucleophilic than TiC.15 (equation 16). 

The synthesis of new 11-deoxyprostaglandin analogs with a cyclopentane fragment in the oo-chain, prostanoid 418, has been accomplished by a reaction sequence involving nitrile oxide generation from the nitromethyl derivative of 2-(oo-carbomethoxyhexyl)-2-cyclopenten-l-one, its 1,3-cycloaddition to cyclopenten-l-one and reductive transformations of these cycloadducts (459). Diastereoisomers of a new prostanoid precursor 419 with a 4,5,6,6a-tetrahydro-3aH-cyclopent[d isoxazole fragment in the oo-chain have been synthesized. Reduction of 419 gives novel 11-deoxyprostanoids with modified a- and oo-chains (460). 

A total synthesis of the sesquiterpene ( )-illudin C 420 has been described. The tricyclic ring system of the natural product is readily quickly assembled from cyclopropane and cyclopentene precursors via a novel oxime dianion coupling reaction and a subsequent intramolecular nitrile oxide—olefin cycloaddition (463). 

The same authors extended the [2 + 2 + 2]-cycloaddition methodology to the use of highly electron-deficient tricarbonyl compounds such as ketomalonates (Equation (33)).360 In that particular case, the reaction does not stop at the initial stage of 277-pyrans 164. Instead, a thermally induced electrocyclic ring opening occurred to form the corresponding cyclopentenes 165 as final product. 

The first examples of transition metal-catalyzed [5 + 2]-cycloadditions between vinylcyclopropanes (VCPs) and 7r-systems were reported in 1995 by Wender and co-workers.10 This [5 + 2]-reaction was based conceptually on the Diels-Alder reaction, replacing the four-carbon, four-7r-electron diene with a five-carbon, four-electron VCP (Scheme 1). Although the [5 + 2]-reaction of VCPs and 7r-systems can be thought of as a homolog of the Diels-Alder [4 +21-reaction, the kinetic stability of VCPs (activation barrier for the thermal isomerization of VCP to cyclopentene has been reported as 51.7 kcal mol-1)11 makes the thermal [5 + 2]-reactions involving VCPs and 7r-systems very difficult to achieve. A report of a thermal [5 + 2]-cycloaddition between maleic anhydride and a VCP has been published,12 but this reaction has not been reproduced by others.13 14 Based on the metal-catalyzed isomerization of VCPs to cyclopentenes and dienes,15-20 Wender and co-workers hypothesized that a metal might be used to convert a VCP to a metallocyclohexene which in turn might be trapped by a 7r-system to produce a [5 + 2]-cycloadduct. Based on its previous effectiveness in catalyzed [4 + 2]-21 and [4 + 4]-cycloadditions (Section 10.13.2.4), nickel(0) was initially selected to explore the potential of VCPs as four-electron, five-carbon components in [5 + 2]-cycloadditions. 

The Lewis acid catalyzed thermal [2 + 2] cycloaddition between 1-cyano-cyclopentene (68) and l-(N,N-diethylamino)-l-propyne (69) afforded the enamine... 

The reactivity of compound 113 toward reactive linear and cyclic dienophiles was reported in a study directed to find a model systems for the proposed [4+2] cycloaddition in the biosynthesis of the natural products brevianamides, paraherquamides, and marcfortines. With DMAD and diethyl azodicarboxylate the formation of 114 and 115 was almost quantitative after 48 h at 80 °C (Cbz = Carbobenzyloxygroup). When relatively unreactive dienophiles such as cyclopentene and cyclohexene were used, harsh reaction conditions and/or a Lewis acid catalyst are necessary for the formation of 116a and 116b (Scheme 16). In contrast, the analogous intramolecular reaction carried out on compound 117 takes place within a few hours at room temperature, even in the absence of a Lewis acid catalyst, to give 118 in 42% yield (Scheme 16) <2000T6345>. 

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. 

Complexes of nickel(II) or magnesium(II) with the chiral ligand DBFOX (Scheme 8) catalyze the DCR of nitrones with a-alkyl- and arylacroleins rendering preferentially the 5-carbaldehyde cycloadducts. However, the reactions with a-bromoacrolein catalyzed by the zinc(II) complex of the same ligand afford isoxazoline -carbaldehydes. The corresponding cobalt(II) complex is also active for the cycloaddition between cyclopenten-l-carbaldehyde and diphenylnitrone. 

Scheme 9 [3+2] Cycloaddition of nitrones with 1-cyclopentene-l-carboxaldehyde...

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