Cycloaddition of alkenes

As was mentioned in Section 13.2, the [27t + 27i] photocycloaddition of alkenes is an allowed reaction according to orbital symmetry considerations. Among the most useful reactions in this categoty, from a synthetic point of view, are intramolecular [27t + 2ti] cycloadditions of dienes and intermolecular [2ti + 2ti] cycloadditions of alkenes with cyclic a, -unsaturated carbonyl compounds. These reactions will be discussed in more detail in Section 6.4 of Part B. 

The photochemical cycloadditions of alkenes and alkynes with aromatic compounds have received by far the most attention. Yields of [2+2] cydoadducts can be good, but reaction times are often long and secondary rearrangement products are common [139, 140, 141,142, 143,144, 145,146] (equations 63-65). The pioneering mechanistic and synthetic work on aromatic photocycloadditions has been reviewed [147],... 

Cycloaddition reactions result in the formation of a new ring from two reactants. A concerted mechanism requires that a single transition state, and therefore no intermediate, lie on the reaction path between reactants and adduct. The most important example of cycloaddition is the Diels-Alder (D-A) reaction. The cycloaddition of alkenes and dienes is a very useful method for forming substituted cyclohexenes.1... 

A pyran ring is formed in the intramolecular Diels-Alder cycloaddition of alkene-tethered enantiopure (lS,2R)-l,2-dihydroxycyclohexa-3,5-diene-l-carboxylic acid derivatives (derived from the biodihydroxylation of benzoic acid). For the three cases illustrated in Scheme 6.246, Mihovilovic and colleagues found that moderate to high yields of the desired cycloadducts could be obtained by exposing a solution of the precursor to microwave irradiation at 135-210 °C for extended periods of time... 

Cycloadditions give rise to four-membered rings. Thermal concerted [2+2] cycloadditions have to be antarafacial on one component and the geometrical and orbital constraints thus imposed ensure that this process is encountered only in special circumstances. Most thermal [2+2] cycloadditions of alkenes take place by a stepwise pathway involving diradical or zwitterionic intermediates [la]. Considerably fewer studies have been performed regarding the application of microwave irradiation in [2+2] cydoadditions than for other kinds of cydoaddition (vide supra). Such reactions have been commonly used to obtain /1-lactam derivatives by cycloaddition of ketenes with imines [18-20,117,118],... 

The well-known Diels-Alder reaction [95,104-106] is a standard method for forming substituted cyclohexenes through the thermally allowed 4s + 2s cycloaddition of alkenes and dienes. In particular, the reaction between ethene and 1,3-butadiene to yield cyclohexene is the prototype of a Diels-Alder reaction (Scheme 28.4). It is now well recognized that this reaction takes place via a synchronous and concerted mechanism through an aromatic boatlike TS [105]. 

Although cycloaddition reactions have yet to be observed for alkene radical cations generated by the fragmentation method, there is a very substantial literature covering this aspect of alkene radical cation chemistry when obtained by one-electron oxidation of alkenes [2-16,18-26,28-31]. Rate constants have been measured for cycloadditions of alkene and diene radical cations, generated oxidatively, in both the intra- and intermolecular modes and some examples are given in Table 4 [91,92]. 

Rothwell and colleagues352 studied the titanium mediated [2 + 2 + 2] cycloaddition of alkenes with monoynes and diynes. Among the reactions studied, the reaction between styrene (29) and diyne 609 in the presence of titanium catalyst 610 proved cleanest (equation 175). The reaction yielded 614 via a [2 + 2 + 2] cycloaddition followed by a titanium mediated suprafacial [1,5] H-shift involving 611-613. The cis relationship between the trimethylsilyl group and the phenyl group indicated that the initially formed titananorbornene 611 had an endo stereochemistry. 

A review of the mechanism of thermal 2 + 2-cycloadditions of activated alkenes to allenes and ketenes has been published. " Stereoselective intramolecular 2 + 2-cycloadditions of alkene-keteniminium salts (19) derived from L-glutamic salts yield... 

The stereochemical outcome of such cycloadditions may be altered by substituents attached to the nitrile oxide-olefin linker. Hassner and co-workers (75,240,253-255) and Kurth and co-workers (256) examined the influence of a stereogenic center a to the dipole in the cycloaddition of alkene-tethered nitrile oxides that feature a sulfur or oxygen atom within the connecting chain (Table 6.13). As expected, the diastereofacial selectivity is increased in the presence of fragments with increasing steric demand. Cycloadditions of thioethers show lower... 

A number of intramolecular cycloadditions of alkene-tethered nitrile oxides, where the double bond forms part of a ring, have been used for the synthesis of fused carbocyclic structures (18,74,266-271). The cycloadditions afford the cis-fused bicyclic products, and this stereochemical outcome does not depend on the substituents on the alkene or on the carbon chain. When cyclic olefins were used, the configuration of the products found could be rationalized in terms of the transition states described in Scheme 6.49 (18,74,266-271). In the transition state leading to the cis-fused heterocycle, the dipole is more easily aligned with the dipolarophile if the nitrile oxide adds to the face of the cycloolefin in which the tethering chain resides. In the trans transition state, considerable nonbonded interactions and strain would have to be overcome in order to achieve good parallel alignment of the dipole and dipolarophile (74,266). 

Chiral aluminium complexes have been used as catalysts for inverse electron-demand 1,3-dipolar cycloadditions of alkenes with nitrones, and the first contribution to this field was pubhshed in 1999 (344). The chiral AlMe-BEMOL (BINOL = 2,2 -bis(diphenylphosphino)-l,l -binaphthyl) complexes 235 were excellent catalysts for the reaction between nitrone 225a and vinyl ethers 232 (Scheme 12.68). The diastereo- and enantioselectivities are highly dependent on the chiral ligand. An exo/endo ratio of 73 27 was observed, and the exo-product was... 

Cycloadditions of alkenes to pyridines will be considered later in Section 2.05.7. 

Most 4,5-dihydroisoxazoles are prepared by cycloaddition of alkenes and nitrile oxides. By variation of the two components, a variety of mono-, bi- and polycyclic products with defined relative configuration is obtainable36. 

Chiral cyclobutanes can be prepared by cycloaddition of alkenes substituted with one or more chiral auxiliary groups. A diastereofacial selectivity of 95% was observed in the diethylalu-minum chloride catalyzed cycloaddition of 1,1-dimethoxyethene (36) with ( — )-dimenlhyl-3-yl fumarate (37).16 The chiral cyclobutane 38 has been used as an intermediate in the synthesis of carbocyclic oxetanocin analogs. 

As in the case of catalyzed cycloadditions of alkenes, reactions of allenes catalyzed by Lewis acids or via vinyl cations proceed more efficiently than their thermal counterparts. Even nonactivated allenes can be induced to react with nonactivated alkenes to give good yields of cyclobutanes. Such reactions could not be carried out under noncatalyzed conditions.1... 

Few syntheses of cyclobutanes by the five minus one strategy starting from a metallacyclopen-tane by elimination of the metal fragment have been reported. Such metallacarbocycles have been postulated as intermediates in the cyclodimcrization of alkenes to give cyclobutanes as an alternative mechanistic interpretation for the orbital symmetry forbidden thermal [2 -1- 2] cycloadditions of alkenes (Houben-Weyl, Vol. E18, pp 843 - 873). 

Reactions by Other Nucleophiles As in the case of the formal cycloadditions of alkenes to allyl cations, the addition of alkenes to gold(I)-activated allenes generates intermediates that determine which cycloaduct formed. Based on this hypothesis, Toste et al. recently developed enantiorich bicycle-[3.2.0] structures by [2+2]-cycloaddition reaction catalyzed by chiral biarylphosphinegold(I) complexes [51]. 

The polar 1,4-cycloaddition of alkenes with 2-hydroxy-5-nitrobenzyl chloride in the presence of tin(IV) chloride yields 6-nitrochromans (69TL5279). The quinone methide, which is protonated under these conditions, undergoes stereospecific syn addition of the alkene. Although in most cases the reaction is regiospecific, ds-pent-2-ene yields a mixture of isomers. 

The photoinduced 1,4-cycloaddition of alkenes to phenanthra-quinone to give substituted 1,4-dioxenes [Eq. (86)] in good yield was first observed in 1944.824 The addition has since then been more fully investigated, and is applicable to a variety of o-quinones and aromatic... 

The use of TiCl2-TADD0Late and Mg(II)-phenanthroline catalysts in asymmetric 1,3-dipolar cycloadditions of alkenes with nitrones has been reviewed.62 The 1,3-dipolar cycloaddition of 3-acryloyloxazolidin-2-one with nitrones catalysed by [TiX2(TADDOLato)] complex shows high regio-, diastereo-, and enantio-selectivity.63... 

Cycloadditions of alkenes and alkynes onto imine cation radicals have been reported, with the cation radicals generated by either PIET mediated by DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone)180, or by TIET mediated by FeCb1066. The reaction is shown in Scheme 77. 

The intermolecular [2 + 2]-cycloaddition of alkenes and alkynes utilizing an iron complex as a catalyst was reported by Rosenblum and Scheck [48]. The application of the [CpFe(CO)2]BF4 complex (Scheme 9.21) gave the desired cyclobutene derivatives 29 in up to 53% yield. 

Cycloaddition of alkenes to the benzene ring does not occur when both molecules are in their ground electronic states. The reaction can only be brought about by photoexcitation of either of the two addends. Three types of photochemical cycloaddition of alkenes to benzene and its derivatives are presently known. Ortho photocycloaddition, also referred to as 1,2-photocycloaddition or [2 + 2] photocycloaddition, leads to bicyclo[4.2.0]octa-2,4-dienes. Meta photocycloaddition, also referred to as 1,3-photocycloaddition or [2 + 3] photocycloaddition, gives triyclo[3.3.0.02 8]oct-3-enes, also named l,2,2a,2b,4a,4b-hexahydrocyclo-propa[crf]pcn(alcnes. Para photocycloaddition, also referred to as 1,4-photocy-cloaddition or [2 + 4] photocycloaddition, results in bicyclo[2.2.2]octa-2,5-... 

Thus [6+2] cycloaddition of alkene with complex 306, bearing an optically active side chain, under irradiation at room temperature afforded the bicyclic compound 307 in 98% de [73]. According to the Woodward-Hoffmann rule, the [6+2] cycloaddition proceeds by irradiation, and is thermally forbidden. However, the cycloheptatriene complex 308 underwent 1,5-hydride shift, followed by [6+2] cycloaddition by heating, to give the tricyclic compound 309 in 90% yield [74], The cycloaddition was applied to the synthesis of /f-cedrene [75]. 

So special reactions are often used to make cyclobutanes. In the next chapter we shall see that thermal cycloadditions of alkenes with ketenes give four-membered rings, but the commonest method is photochemical cycloaddition. You are already aware that Diels-Alder reactions (chapter 17) occur easily when a diene 6 and a dienophile 7 are heated together and six-membered rings 8 are formed. Have you ever wondered why four-membered rings 9 are not formed instead Orbital symmetry allows cycloadditions involving six Ti-electrons but not those involving four 7r-electrons.2... 

The cycloaddition of alkenes with metal alkylidene complexes remains the most common entry into the metallacyclobutane structural class. Consistent with metallacyclobutane intermediacy in the olefin metathesis reaction, the [2+2] cycloaddition is generally reversible a propensity for cycloreversion (Section 2.12.6.2.4), however, can significantly limit the utility of metallacyclobutane complexes as intermediates in other synthetic transformations. 

Frontier Orbital Interactions in the Transition States of the Unknown One-Step Cycloadditions of Alkenes or Alkynes to Alkenes... 

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