Intramolecular processes cycloadditions

Other examples of [2C+2S+1C0] cycloaddition reactions have been described by Herndon et al. by the use of chromium cyclopropyl(methoxy)carbenes. These complexes react with alkynes releasing ethene and forming cyclopenta-dienone derivatives, which evolve to cyclopentenone derivatives in the presence of chromium(O) and water [122] (Scheme 76). This reaction has been extended to intramolecular processes and also to the synthesis of some natural products [123]. These authors have also described another process involving a formal [2C+2S+1C0] cycloaddition reaction. Thus, the reaction of methyl and cyclo-propylcarbene complexes with phenylacetylene derivatives does not afford the expected benzannulated products, and several regioisomers of cyclopentenone derivatives are the only products isolated [124] (Scheme 76). 

In contrast to the intramolecular process, simple allenes do not participate in the intermolecular [5 + 2]-reaction with VCP 18. However, when a second functionality is incorporated into the allene, an efficient and facile cycloaddition occurs, presumably assisted by a directing effect of the secondary functional group. The [5 + 2]-reaction also works with styrenyl- and cyano-substituted allenes as directing groups (Scheme 12). As would be expected from... 

The [3+2] cycloaddition of azides to double and triple bond systems has found considerable interest over the last couple of years. The reaction can either be performed under thermal conditions or by copper(i) catalysis <2001AG(E)2004, 2002AG(E)2596>. In an attempt to broaden the chemistry of such cycloaddition processes, Sharpless et al. reported the generation of tetrazole derivatives 61 by an intramolecular process (Scheme 12). In... 

Several routes to the pyrrolo[l,2-f][l,2,3]triazole skeleton have been described. Intramolecular dipolar cycloaddition of azido-alkenes or alkynes seems to be the most convenient process, although the cyclization efficiency seems to be highly substrate dependent (Scheme 16) <2002JA2134, 2003T1477, 2005SL2187, 2005TL8639>. The formation of this bicyclic system by an intramolecular Heck reaction is an attractive alternative. The recent syntheses of sulfamides by intramolecular cyclization of alkenes or allenes offer a complementary route to the classical... 

The photochemistry of phthalimide systems was thoroughly investigated by many groups over the last two decades. This chromophore shows a broad spectrum of reactivity leading mainly to cycloaddition and photoreduction products by either intermolecular or intramolecular processes. In the presence of electron donors, the electronically excited phthalimide could also undergo electron transfer and act as an electron acceptor. 

Detailed mechanistic information concerning an intramolecular arylalkene cycloaddition yielding cyclobutane derivatives via a radical cation process gener-... 

Diazoacetamides undergo intramolecular cyclopropanation with similarly high enantios-electivities (Eq. 4) [33, 36, 37]. In these cases, however, competition from intramolecular dipolar cycloaddition can compHcate the reaction process. Therefore, the use of R = Me or Bu has been required to achieve good yields of reaction products. Representative examples of applications of chiral dirhodium(II) carboxamidates for enantioselective intramolecular cyclopropanation of diazoacetamides are compiled in Scheme 15.2. 

The same group has also reported the use of dithiane functionalized olefinic aldehydes in an intramolecular process. Treatment of 289 with the secondary amine 290 led to the formation of the intermediate ylide 291, which delivered a range of tricyclic products (292) in high material yield as essentially a single stereoisomer after in situ cycloaddition (Scheme 3.95). 

Side reactions that occur with intramolecular cycloaddition, such as linear oligomerization or dimerization of the nitrile oxide, are not very common when shorter chain lengths n < 1) are used due to the entropically favored intramolecular process. A rather unusual result in this regard involves the formation of a fused cyclooctane instead of the less-strained six-membered ring (also fused) in the cycloaddition of the nitrile oxide derived from p-naphthoquinone (Scheme 6.43). This result is consistent with the effect of electron-withdrawal in the enedione part, leading to increased reactivity (247), and also reflects the known sluggishness of cyclohexenes towards nitrile oxides (cf. Section 6.2.1.2). 

The transition state of singlet carbene cycloaddition to alkenes involves an electrophilic approach of the vacant p orbital to the n bond of alkenes. By contrast, the first step of the triplet addition process may involve the in-plane a orbital of the carbene. As in the case of C—H insertion (see Section 5.1), the difference in the transition structure between the singlet and triplet cycloaddition becomes important in the intramolecular process, especially when approach to a double bond is restricted by ring strain. Direct photolysis of ( )-2-(2-butenyl)phenyldiazomethane (99) in the presence of methanol gives l-ethenyl-l,la,6,6fl-tetrahydrocycloprop [fljindene [100, 29%, (E/Z)= 10 1] and l-(2-butenyl)-2-(methoxymethyl)benzene (101, 67%). Triplet-sensitized photolysis results in a marked increase in the indene (52%, EjZ) = 1.3.T) at the expense of the ether formation (4%) (Scheme 9.30). On the other hand, direct photolysis of phenyldiazomethane in an equimolar mixture of... 

Further reactions that are highly suited to the synthesis of cyclohexane derivatives, such as cycloaddition processes, 1,3-dipolar additions, and Diels-Alder cyclizations, have been used extensively. In the latter set, carbohydrate-based dienes or dienophiles have been employed and, in addition, intramolecular processes have provided highly suitable means of synthesizing complex polycyclic systems. 

Diazo compounds have been extensively used in the preparation of three-membered carbocycles either as carbene sources or as precursors for 1-pyrazolines or 3//-pyrazoles. Nitrogen extrusion from pyrazolines is particularly valuable for the synthesis of alkylcy-clopropanes, since the direct carbene route is impractical, as a matter of fact, owing to rapid intramolecular processes in alkylcarbenes. The cycloaddition of diazo compounds to unsaturated bonds to give 1-pyrazolines and 3/f-pyrazoles usually proceed in a concerted manner, and hence is stereospecific. In the subsequent nitrogen extrusion from the adducts,... 

While virtually all of the research described above has focused on the inter-molecular cycloaddition of azomethine ylides, the intramolecular process holds considerable promise for the synthesis of polycyclic natural products. The Pfaltz group reported an intramolecular catalytic asymmetric cyclization of aryl iminoesters 112 using a complex of silver acetate with PHOX type ligand 100 (Scheme 2.29,... 

Diels-Alder Reactions. Chiral a,p-unsaturated imides participate in Lewis acid-promoted Diels-Alder cycloaddition reactions to afford products in uniformly excellent endo/exo and endo diastereoselectivities (eq 50 and 51). Unfortunately, this reaction does not extend to certain dienophiles, including methacryloyl imides, p,3-dimethylacryloyl imides, or alkynic imides. Cycloadditions also occur with less reactive acyclic dienes with high diastereoselectivity (eq 52). Of the auxiliaries surveyed, the phenylalanine-derived oxazolidinones provided the highest diastereoselectivities. This methodology has been recently extended to complex intramolecular processes (eq 53). In this case, use of the unsubstituted achiral oxazolidinone favored the undesired diastereomer. 

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