Higher Cycloadditions

In this section, those domino reactions are described which start with a cycloaddition not of the [4+2] and [3+2] types. The variety referred to is quite high consequently, in addition to the well known [2+2] scheme, [4+3] cycloaddition and the more exotic [5+2] cycloaddition are also outlined. 

West and coworkers developed two new domino processes in which a [4+3] cycloaddition (Nazarov electrocyclization) of l,4-dien-3-ones is succeeded by either an 

As main product, 4-219 (56%) was obtained together with 9% of a stereoisomer. The reaction can also be performed as a three-component reaction using 4-216, 4-217 and 4-218, which gave a mixture of 4-219, 4-220 and 4-221. The latter transformation indicates that intermediates such as 4-222 or 4-223 might play a role in this domino process. 

A remarkable domino process which leads to products of high complexity with good stereoselectivity was observed by Engler and coworkers by treating a mixture 

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Chiral BOX-zinc(II) complexes can also catalyze the cycloaddition reaction of glyoxylates with, e.g., 2,3-dimethyl-l,3-butadiene and 1,3-cyclohexadiene [36]. The reaction gave for the former diene a higher cycloaddition product/ene product ratio compared with the corresponding chiral copper(II) complexes the ee, however, was slightly reduced. For the reaction of 1,3-cyclohexadiene slightly lower yield and ee were also found. 

The cycloaddition reactions that involve more than six Tt-electrons are generally referred to as higher cycloadditions. These reactions provide a convenient synthesis of medium-sized rings, which are otherwise difficult to obtain by other methods. 

Higher cycloaddition reactions, using VCPs as the five-carbon unit, have also been developed. Rhodium-catalyzed carbonylation of VCP-enes resulted in [5+2+1] annulation to furnish eight-membered ring enones (Scheme 2.46) [66]. 

The 1,3-dipoles consist of elements from main groups IV, V, and VI. The parent 1,3-dipoles consist of elements from the second row and the central atom of the dipole is limited to N or O [10]. Thus, a limited number of structures can be formed by permutations of N, C, and O. If higher row elements are excluded twelve allyl anion type and six propargyl/allenyl anion type 1,3-dipoles can be obtained. However, metal-catalyzed asymmetric 1,3-dipolar cycloaddition reactions have only been explored for the five types of dipole shown in Scheme 6.2. 

The above described approach was extended to include the 1,3-dipolar cycloaddition reaction of nitrones with allyl alcohol (Scheme 6.35) [78]. The zinc catalyst which is used in a stoichiometric amount is generated from allyl alcohol 45, Et2Zn, (R,J )-diisopropyltartrate (DIPT) and EtZnCl. Addition of the nitrone 52a leads to primarily tmns-53a which is obtained in a moderate yield, however, with high ee of up to 95%. Application of 52b as the nitrone in the reaction leads to higher yields of 53b (47-68%), high trans selectivities and up to 93% ee. Compared to other metal-catalyzed asymmetric 1,3-dipolar cycloaddition reactions of... 

Nitronates derived from primary nitroalkanes can be regarded as a synthetic equivalent of nitrile oxides since the elimination of an alcohol molecule from nitronates adds one higher oxidation level leading to nitrile oxides. This direct / -elimination of nitronates is known to be facilitated in the presence of a Lewis acid or a base catalyst [66, 72, 73]. On the other hand, cycloaddition reactions of nitronates to alkene dipolarophiles produce N-alkoxy-substituted isoxazolidines as cycloadducts. Under acid-catalyzed conditions, these isoxazolidines can be transformed into 2-isoxazolines through a ready / -elimination, and 2-isoxazolines correspond to the cycloadducts of nitrile oxide cycloadditions to alkenes [74]. 

The reactivity of the unsaturated system of oxepin gives rise to a variety of cycloaddition reactions. A number of 3,6-bridged oxepins have been reacted with peracids to give 2,3-ep-oxyoxepins i,129 154.213.218 At higher temperature, the 2,3,6,7-diepoxy derivatives 2 are formed.164... 

H-Azepines 1 undergo a temperature-dependent dimerization process. At low temperatures a kinetically controlled, thermally allowed [6 + 4] 7t-cycloaddition takes place to give the un-symmetrical e.w-adducts, e.g. 2.231-248-249 At higher temperatures (100-200°C) the symmetrical, thermodynamically favored [6 + 6] rc-adducts, e.g. 3, are produced. These [6 + 6] adducts probably arise by a radical process, since a concerted [6 + 6] tt-cycloaddition is forbidden on orbital symmetry grounds, as is a thermal [l,3]-sigmatropic C2 —CIO shift of the unsym-metrical [6 + 4] 7t-dimer. 

It has been established that alkoxy alkenylcarbene complexes participate as dienophiles in Diels-Alder reactions not only with higher rates but also with better regio- and stereoselectivities than the corresponding esters [95]. This is clearly illustrated in Scheme 51 for the reactions of an unsubstituted vinyl complex with isoprene. This complex reacts to completion at 25 °C in 3 h whereas the cycloaddition reaction of methyl acrylate with isoprene requires 7 months at the same temperature. The rate enhancement observed for this complex is comparable to that for the corresponding aluminium chloride-catalysed reactions of methyl acrylate and isoprene (Scheme 51). 

It is believed that clay minerals promote organic reactions via an acid catalysis [2a]. They are often activated by doping with transition metals to enrich the number of Lewis-acid sites by cationic exchange [4]. Alternative radical pathways have also been proposed [5] in agreement with the observation that clay-catalyzed Diels-Alder reactions are accelerated in the presence of radical sources [6], Montmorillonite K-10 doped with Fe(III) efficiently catalyzes the Diels-Alder reaction of cyclopentadiene (1) with methyl vinyl ketone at room temperature [7] (Table 4.1). In water the diastereoselectivity is higher than in organic media in the absence of clay the cycloaddition proceeds at a much slower rate. 

Silica gel [11] or alumina [11a, 12] alone, or silica and alumina together modified by Lewis-acid treatment [13] and zeolites [14], have been widely used as catalysts in Diels-Alder reactions, and these solids have also been tested as catalysts in asymmetric Diels-Alder reactions [12,13b,14]. Activated silica gel and alumina at 140 °C were used [15] to catalyze the asymmetric cycloaddition of (-)-menthyl-N-acetyl-a, S-dehydroalaninate (3) (R = NHCOMe) with cyclopentadiene in the key step for synthesizing optically active cycloaliphatic a-amino acids. When the reactions were carried out in the absence of solvent, a higher conversion was obtained. Some results are reported in Table 4.5 and compared with those obtained by using silica and alumina modified by treatment with Lewis acids. Silica gel gives a reasonable percentage of conversion after 24 h with complete diastereofacial selectivity in exo addition. 

A higher regioselectivity was observed [70c] in the cycloaddition in water at 25 °C of diene surfactant 103 with 100 (Equation 4.14, 104/105 = 6.7 1) in agreement with the expectation that the organizational ability of aqueous aggregates is higher at lower temperatures. 

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