Components in Cycloaddition Reactions

Thermal or catalytic cyclodimerization of iminoboranes is obviously a [2 -I- 2]-cycloaddition (Section IV). A mixture of two different iminoboranes may be stabilized by formation of three different cyclodimers. If the relative stability of the two iminoboranes, however, differs distinctly, the mixed cyclodimer will be formed preferentially by 

Reaction of aldehydes and ketones with iminoboranes has been widely investigated. Conditions for the [2 + 2]-cycloaddition between XBNR and R R CO are relatively good stability of the iminoborane and lack of enolic protons in the oxo compound [Eq. (46)] 14, 19). Relatively less stable iminoboranes, but in some cases the stable ones too, may react with 0X0 compounds by a total opening of the B=N triple bond [Eq. (43)], presumably via a [2 + 2]-cycloaddition [Eq. (42)] (Section V,D). A relatively stable iminoborane and a ketone containing enolic protons may yield an open-chain product, probably through a six-membered cyclic transition state [Eq. (46b)] 19). 

Alternative reaction pathways, corresponding to Eq. (46), are also observed in the reaction of iminoboranes with iminoalkanes the ligand R bonded to the iminoalkane nitrogen atom, seems to govern the reaction path [Eq. (47)] 9, 19). Offering the two C=N double bonds of 

Me2C=N—N=CMe2 to the attack of iPrB=NiPr, both possible paths are realized [Eq. (48)] (19). 

The aminoiminoborane CgHigN—B=N Bu gives [2+2]-cycloadducts with the heteroallenes Y=C=Y [Eq. (49)]. The cycloadducts can be transformed thermally as well as photolytically into the novel four-membered ring systems (C9HigNBY)2 (Y = O, S, Se), according to Eq. (42b) and (42c) (79). 

---

By far the most important property of benzo[c] furans is their capacity to act as 471-components in cycloaddition reactions. Whereas the reactions described before 1969 were almost always of the Diels-Alder type, more recent investigations have shown that they can also participate in [7 4 + 714]-and [714 + TCgj-addition (Section IV,C). In this chapter Diels-Alder reactions will be discussed. Benzo[c]furans have been used for two main purposes. First, Diels-Alder adducts with olefinic compounds can conveniently be dehydrated to naphthalene derivatives or higher condensed hydrocarbons not easily accessible by other methods second, benzo[c]furans are excellent... 

Thiophene 1,1-dioxide can function as either a 27r-component or a 4fl--component in cycloaddition reactions. 

Sulfenes are reactive 27r-components in cycloaddition reactions and treatment of methanesulfonyl chloride with triethylamine in the presence of (CF3)2C=NCOPh gives the 1,2,5-oxathiazine (119) via a formal [4+2] cycloaddition of sulfene to the heterodiene (69IZV2059). 

Vinylindoles are also efficient 47r-components in cycloaddition reactions and provide the corresponding [c]-annelated carbazoles which react, for example, with NPMI, MA, and quinones [82CJC419 83IJC(B)1004 88HCA1060] (Scheme 6). Although in the more usual cases the result of... 

Indene can participate as the cne component in [4 + 2] and [2 + 2] cycloaddition reactions with diazene dicarboxylates and triazolediones. Aryl-substituted alkenes, however, can participate as the diene components in cycloaddition reactions with the same diazene compounds, although the reaction can follow different pathways depending on the nature of the substituents on the vinyl and phenyl groups. 

Dihydrooxazoles such as 263 have also been prepared <2004T7591> via an oxidative decarboxylation and elimination of the corresponding oxazolidine -carboxylic acid 262 (Scheme 77). The oxazolidine-4-carboxylic acids were in turn derived from L-serine. The thermal oxidative decarboxylation using lead tetraacetate was reported to be higher yielding and more practical than the analogous electrochemical version. Dihydrooxazoles 263 have been extensively used as chiral olefmic components in cycloaddition reactions and these reactions are discussed in Section 4.04.6.2.1. 

A very powerful and elegant methodology intensely developed in recent years for the construction of five-membered ring systems, e.g. of cyclopentanoid natural products, is based on the in situ formation of highly reactive Cj intermediates from a variety of synthetic precursors. These intermediates 1 can then serve as three-earbon, 2n-electron (Y = Hj) or 4 -electron (Y = CH, O) components in cycloaddition reactions, specifically of the [3-1-2] type, with various carbon-carbon - or carbon-heteroatom multiple bonds as 2rt-components. 

While many of the heterocyclic systems under discussion contain C=0, C=S or C=N double bonds, and these functions are capable of acting directly as, or forming part of, 2n or 4 components in cycloaddition reactions, no examples have been reported. 

There is considerable interest in the use of small heterocycles as 2ir components in cycloaddition reactions but studies have been limited as many heterocycles are reluctant to undergo such reactions. 2-Dimethylamino-l,3-thiazoles do react with hindered ketenes such as (111). The ratio of cycloaddition products (112) to substitution product (113) was 8 1. 

Danishefsky found that alkoxy- and silyloxy-substituted dienes such as 47 (Danishefsky s diene see Scheme 17.10) sei-ve as excellent 4jr-components in cycloaddition reactions with aldehydes catalyzed by a broad range of Lewis acids [43, 44, 106, 107]. The cycloaddition between 47 and the ribose-derived aldehyde 200 in the presence of the NMR shift reagent Eu(fod)3 (201) as a mild, Lewis acidic catalyst [108] furnished 202 as the only observed product in 85 % yield (Equation 23) [109]. Danishefsky utilized this family of oxygen-substituted dienes to access natural and unnatural hexoses [44, 106, 110]. As a demonstration of the general synthetic strategy, diene 203, bearing a 1-phenmenthyl auxiliary, was utilized in combination with Eu(hfc)3 (204) to prepare L-glucose (206, Scheme 17.28). 

Five-membered ring heterocycles can be the result of cycloaddition reactions of ADC compounds acting as 2n components with 1,3-dipoles, or as 47t components in cheletropic reactions. They can also result from nucleophilic attack on the ADC compound, followed by ring closure of the initial adduct. 

The thermally allowed [8 + 2] cycloaddition reactions may be considered as the 10tt analogs of the Diels-Alder reaction in which the diene component has been replaced by a tetraene component. Like trienes in the [6 + 4] cycloaddition reactions, the 87t tetraenes must satisfy certain requirements concerning geometry in order to be able to participate in an [8 + 2] cycloaddition. For example, tetraenes 518 and 519 can undergo an [8 + 2] cycloaddition, whereas an [8 + 2] cycloaddition with 520 is virtually impossible. Due to its fixed -system, 519 is more reactive in cycloaddition reactions than 518 and is therefore more often encountered in the literature. [8 + 2] Cycloadditions have been applied only... 

Bicyclopropylidene (1) also reacts with activated alkenes under transition-metal catalysis. With electron-deficient alkenes under nickel(O) catalysis, the [2-1-2] cycloadduct 263 was the main component in the reaction mixture [2b, 150]. Under palladium(O) catalysis, formal [3-1-2] cycloaddition of electron-deficient (Scheme 60) as well as strained alkenes can be achieved exclusively... 

Fluorinated cyclopentadienes would be ideal components for cycloaddition reactions leading to fluorinated carbocycles. However, there are few reports of such species. Treatment of the thallium(I) salt of cyclopentadiene with Select-fluor led to the formation of fluorocyclopentadiene (Eq. 118), which reacted with dienophiles to afford cycloadducts in the syn orientation [317]. 

The double bonds in non-aromatic heterocyclic systems can in principle participate in cycloaddition reactions either as 27t- or 4ir-components. Although not many examples have been reported, there are cases where the heterocyclic ring acts as a diene or dienophile. 

Another way to look at this resuft comes from recognizing the special entropy problem involved in cycloaddition reactions. A very precise orientation of the two molecules is required for two bonds to be formed at once. These reactions have large negative entropies of activation (Chapter 41)—order must be created at the transition state as the two components align with one another. The through-space attractive HOMO/LUMO interaction between the two molecules can lead to an initial association that can be compared to a squishy sandwich with... 

It is possible to give a frontier orbital description of a [3,3] -sigmatropic rearrangement but this is not a very satisfactory treatment because two reagents are not recognizing each other across space as they were in cycloadditions. There are three components in these reactions—two nonconjugated K bonds that do have to overlap across space and a O bond in the chain joining the two k bonds. 

By suitable substitution the enaminones can often serve as precursors for heterocycles and preparation of indoles, carbazoles, quinolines, acridines and phenaNthridines can be achieved easily. However, this part of enaminone chemistry can lead to surprising and unexpected reactions if the multifunctional properties of the enaminones are ignored, e.g. ring contraction, ring expansion and other rearrangements are observed. In some cases jft-ketoenamines react as the ene-component in cycloaddition. Enaminones are even suitable synthones for building aromatic rings. 

In cycloaddition reactions, frontier orbital analysis considers the interaction of the HOMO of one component and the LUMO of the other. 

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. 

The Diels-Alder reaction is reversible, and many adducts, particularly those formed from cyclic dienes, dissociate into their components at higher temperatures. Indeed, a refro-Diels-Alder reaction is the principal method for preparing cyclopenta-diene prior to its use in cycloaddition reactions. 

Alkenyl sulfides are known to react with some labile electron-deficient olefins such as methyl vinyl ketone in the presence of AlCl3 to form cyclobutanes [25]. In the present chiral titanium-promoted asymmetric reaction, alkenyl sulfides can also be employed as electron-rich components. 2-Ethylthio-l-propene (7a) reacts with 2a in the presence of a catalytic amount of the chiral titanium reagent, giving the diastereomeric [2-1-2] cycloaddition products 8a and 9a in 51% (>98% ee) and 19% (79% ee) yields, respectively (Scheme 7 and Table 2). Although 2-ethylthio-l-propene (7a) is known as a good ene component in the reaction with carbonyl compounds, 3-(3-(methoxycarbonyl)-5-ethylthio-5-hex-enoyl)-l,3-oxazolidin-2-one, an ene product, is obtained only in 16% yield as a side product. 

A review of the methods for the generation of cyclic carbonyl ylides from intramolecular carbene additions has recently appeared [64]. This intermediate was first exploited as the An component for cycloaddition reactions by Ibata [65]. ort/io-Disubstituted carboalkoxy aryl diazoketones such as 54 were decomposed by copper complexes, generating six-membered ring carbonyl ylides. These transient intermediates underwent subsequent intermolecular cycloadditions in the presence of ethylenic and acetylenic reagents to give predominantly exo products containing the oxabicyclo[3.2.1] nucleus, Eq. 38. 

---