Cyclopentenes, addition cycloaddition with

The introduction of a bulky, optically active amino function at C-2 of 4-phenyl-l-thiabutadiene and activation by the addition of AcCl prior to cycloaddition with Wphenylmaleimide, known to exhibit a high endo preference, results in the formation of two diastereomers. However, the exo product is the major component and indeed this diastereo-mer is the sole adduct when cyclopentene is used as the dienophile. Calculations point to a preference for exo addition from the same face of the molecule as the naphthyl moiety and this is supported by the observed R stereochemistry at the three chiral centers in the cyclopenta[A]dihydrothiopyran 434 (Scheme 140) <1996TL123>. 

Bicyclo[3,2,0]heptane Derivatives.— These are principally prepared by the [2 -I- 2] cycloaddition of a cyclopentene with another unsaturated unit. Typical combinations which have been routinely applied in syntheses are photochemical addition of a cyclopentene to an olefin or acetylene and thermal addition of a cyclopentadiene with an olefin, a keten, or an acetylene. In the last case, cycloaddition with an alkyne is complicated both by competition between [2 -h 2] and [2 + 4] modes of addition and by the possibility of a second addition of cyclopentadiene to the initially formed bicyclo[3,2,0]heptadiene. The results for diphenylacetylene and cyclopentadiene are shown in Scheme 31. 

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]. 

Many [2 + 2] cycloadditions that do not occur by simply heating the possible reactants can be achieved by irradiation with ultraviolet light. The following example, [2 + 2] addition of 2-cyclopentenone to cyclopentene, occurs photochemically but not thermally ... 

Enantioselective total syntheses of (-)-6-epitrehazolin and (+)-trehazolin were achieved by the synthesis of 275, which began with an asymmetric heterocycloaddition between [(benzyloxy)methyl]cyclopentadiene (263),108 prepared from thallous cyclopentadienide, and the acylnitroso compound arising from in situ oxidation of (,S )-mandelohydroxamic acid (264) with tetrabutylammonium periodate. Cycloaddition led to a mixture of 265 and its diastereomer (Scheme 35).109 The inseparable mixture was reduced to afford cyclopentenes 266 and 268 in 40% and 11 % overall yields, respectively, from thallous cyclopentadienide. Catalytic osmylation of 266 favored syn addition, while the osmylation of diacetate 267 was more selective and nearly quantitative, affording, after acetylation, compounds 270 and 269 in >5 1 ratio. 

The reactivity of these promising building blocks has very recently been reviewed by de Meijere S therefore only a few principles will be discussed in this text. Treatment with n-butyllithium as outlined in equation 187 will give certain functionalized alkynylcyclopro-panes , which can serve as active components in cycloadditions or reactions with olefins in the presence of Co2(CO)g. The latter [2 + 2 + l]-addition provides cyclopropyl cyclopentenones capable of undergoing vinylcyclopropane-cyclopentene rearrangement. 

Several approaches to the taxane skeleton (97) have been published recently (see also reference 9). All have involved (2+2)- cycloaddition of the type reported by Berkowitz et ai. who have added cyclopentene and cyclohexene to the enone (98) to yield the cycloadducts (99). Successful addition of the alkene (lOO) to the same enone yields the ring-opened adduct (101). In a similar fashion the intramolecular addition of the enone (102) affords a (2+2)-adduct which can be treated with base to provide a route to the skeleton of the same natural product. ... 

Some years ago Cornelisse reported that deuteration of alkyl benzenes results in a deuterium isotope effect upon the quantum yield of the meta photocycloaddition reaction with alkenes. In a new report the same group has published an analysis describing how the observed isotope effect upon the reaction quantvun yield can be ascribed to a kinetic deuterium isotope effect on the excited state reaction and distinguished from an effect upon the unimolecular photophysical modes of decay of the excited state. In addition, it is reported that when the quantum yield of meta photocycloaddition of cyclopentene to alkyl benzenes is measured using a mixture of deuterated and non-deuterated benzenes, the quantum yield is arene concentration dependent.The authors argue that this arises from competition between cycloaddition and the formation of mixed excimers between deuterated and non-deuterated alkyl benzenes which dissociate to yield excited deuterated alkyl benzene and ground state non-deuterated alkyl benzene preferentially. 

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. 

In addition to the trihalo compounds, many other 1,2,4-triazines have been found to react with cyclopentene, cyclohexene, cycloheptene and cyclooctene to give condensed pyridines. In most cases, 1,4-benzoquinone is added to oxidize the initially formed dihydropyridines and to prevent a second [4 I 2] cycloaddition.386 Other 1,2,4-triazines also react with bicyclo[2.2.1]hept-2-ene to give either the condensed pyridines and/or the bisadducts. The ratio of the two products depends on the reaction conditions and the relative proportions of the reactants.386 For a detailed survey, see Houben-Weyl, Vol. E7b, p471ff. 

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 1,3-cycloaddition of ethylenes to benzene and its derivatives, giving rise to dihydrosemibullvalenes, has been known for a number of years and the reaction has recently been reviewed.84 The reaction with cyclopentene as olefin has been the subject of several earlier reports.10 Its light-induced addition to anisole can be used as a stereospecific synthesis of perhydroazulenes 35 the adduct (18) is formed in 85% yield. Its consumption of only one mole of hydrogen on catalytic hydrogenation and its failure to undergo photosensitized decomposition have been... 

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