Monocyclic cyclization reactions

Intramolecular electron transfer initiated cyclization reaction of 7V-allyliminium salt systems may also generate 3-pyrrolidinyl ethers or alcohols in monocyclic and bridged or fused bicyclic systems (e.g. equations 63 - 65)122,123. 

A variety of orthogonal combinations of protecting groups is available for the synthesis of monocyclic peptides on resin i339 343 They must satisfy an additional level of selectivity that is required upon assembly of the fully protected peptide on resin, which enables the subsequent regioselective chemistry to be performed at the functionalities involved in the cyclization reaction while the substrate is still bound to the resin and protected at all residual functions. 

A novel approach to enantiopure spirocyclic (3-lactams has been developed by Alcaide et al. [106] using different intramolecular metal catalyzed cyclization reactions with monocyclic unsaturated alcohols 142 (Scheme 35). Ring-closing metathesis is one of the most powerful and reliable methods to construct a ring system. Transformation of alcohols in diolefin precursors followed by ring-closing... 

All the approaches discussed in Sections 13.16.9 and 13.16.10 were widely applied to the synthesis of 1,3,5-triazepine heterocyclic ring. For the monocyclic and fused compounds, the [1+6] and [3+4] cyclization reaction and the azine ring expansion are the most popular routes (for additional information on the early reports, see CHEC-II(1996)). The bridged derivatives, such as hexaazaisowurtzitanes 5 (Figure 1), are available by multicomponent condensation. 

The most common approaches to monocyclic and fused thiadiazepines are based on one-component (Schemes 17 and 21), [1+6] and [3+4] cyclization reactions. For the detailed information on two latter types of transformations published before 1994, see CHEC-II(1996). 

The range of monoterpenes encountered is extended considerably by cyclization reactions, and monocyclic or bicyclic systems can be created. Some of the more important examples of these ring systems are shown in Figure 5.11. Such cyclizations would not be expected to occur with the precursor geranyl diphosphate, the E stereochemistry of the double bond being unfavourable for ring formation (Figure 5.9). Neryl PP or linalyl PP, however, do have favourable stereochemistry, and either or both... 

Numerous methods of preparing bicyclic systems from monocyclic precursors have been reported and four general strategies can be identified. These are (i) intermolecular cyclization reactions which do not involve 1,3-dipolar cycloaddition reactions (ii) intermolecular 1,3-dipolar cycloaddition reactions (iii) nonoxidative intramolecular cyclizations and (iv) oxidative intramolecular cyclization reactions. These four general methodologies are now considered. 

The 32-membered ditopic hexaaza monocycle 16 was obtained in 47 % yield by Lehn and Hosseini [33] in an analogous direct cyclization reaction using CS2CO3 in DMF as solvent. 

Recent advances in the synthesis of trans-iused polycyclic ethers by hydroxy epoxide cyclization reactions via monocyclic epoxonium ion intermediates and ether ring expansion reactions via bicyclic epoxonium ion intermediates are described in a review by Fujiwara and Murai. Natural trans-iu eA polycyclic ethers (e.g., brevetoxin A and ciguatoxin), produced by marine sources such as dinoflagellates, are hypothesized to be constructed from the corresponding polyepoxide precursors by a cascade of ring-closure reactions, which has prompted much work in the development of new methods for the construction of cyclic ethers from epoxides <2004BCJ2129>. 

This method allows the performance of tandem cyclization reactions. The dienic iodide 54, after intramolecular carbozincation and iodinolysis, gives the bicyclic product 56 (85% cis ring junction > 99%, exo/endo = 64 36) and the monocyclic trans product 55 (15%) as described in Scheme 7-48 [52]. 

Bridged /rauj-decalin-2-yl radicals are formed in cyclization reactions of bicyclic iodolac-tones55. The stereoselectivity in hydrogen-abstraction reactions is very similar to reactions of unbridged, monocyclic radicals with equivalent a- and /Fsubstituents. The bridging lactone unit, therefore, seems to have little influence on the sleric course of the reaction, and preferential attack from the axial side occurs. Axial substituents in / -position to the radical center further increase the selectivity and only the product arising from axial attack is found. 

The intramolecular cyclization reaction of p-halohydroxamates 211 or p-hydroxyhydroxamates 212 (Fig. 6), has been recognized by several research groups as being an efficient method for the construction of the azetidinone ring, and has found widespread utility in the synthesis of either monocyclic and bicyclic P-lactam antibiotics including the PS-5 carbapenem antibiotic [91]. 

In 2009, the Christmann group reported the application of a dienamine intermediate for Rauhut-Currier-type reactions (775). In this case, the a-position of the dienamine acts as the nucleophile in an intramolecular cyclization reaction giving access to functionalized monocyclic compounds. The applicability of this strategy was illustrated in the synthesis of (7 )-rotundial (193), a mosquito repellent from the leaves of Vitex rotundifolia (175). Hence, an organocatalytic Rauhut-Currier-type reaction of dialdehyde 192 catalyzed by 20 mol% (5)-138 gave (7 )-rotundial (193) directly in good enantioselectivity, albeit in only a moderate yield (Scheme 46). 

Development of highly efficient catalytic processes for the synthesis of natural and unnatural compounds of medicinal interest or useful as intermediates for functional materials is a central focus in modern organic synthesis. One of the most efficient approaches to such methodology developments is to apply transition-metal catalyzed cyclization reactions for the transformations of simple starting materials into monocyclic, bicyclic, and polycyclic scaffolds that can be further elaborated into specific targets. 

The diastereoselectivity in the Pd(II)-LiX-CuX2-catalyzed cyclization of 2 -alkenyl 2-alkynoates is similar to that in the Pd(II)-LiX-catalyzed cyclization of 4 -het-eroatom-2 -alkenyl 2-alkynoates. The similar diastereoselectivity was observed in the synthesis of a-alkylidene-y-butyrolactams. The diastereoselectivity is further supported by the cascade cyclization reaction. A monocyclic product was obtained in the reaction of l, 5 -hexadien-3 -yl propynoate. The failure of the second cyclization might be due to the trans-configuration of the /S.y-disubstituents in the product. The reaction of r,5 -hexadien-3 -yl 3-substituted 2-aIkynoates under the same conditions yielded the cw-fused bicyclic a-(Z)-chloroalkylidene- y-butyrolactone derivatives implying the cw-diastereochemistry of the /3,y-disubstituents in the first cyclization (Scheme 16). 

Finally, solvolysis of diene 71 gave cyclohexanol 72 and m-decalins 73 as the most notable products (Steroids-14). Once again, the stereochemistry of these products suggest that at ft-addition of electrophile and nucleophile across the r -olefin was dictating the stereochemical course of cyclization reactions. This experiment also showed that the solvolyses of 66 and 71 do not pass through a common monocyclic intermediate. 

The early Escherunoser-Stork results indicated, that stereoselective cyclizations may be achieved, if monocyclic olefins with 1,5-polyene side chains are used as substrates in acid treatment. This assumption has now been justified by many syntheses of polycyclic systems. A typical example synthesis is given with the last reaction. The cyclization of a trideca-3,7-dien-11-ynyl cyclopentenol leads in 70% yield to a 17-acetyl A-norsteroid with correct stereochemistry at all ring junctions. Ozonolysis of ring A and aldol condensation gave dl-progesterone (M.B. Gravestock, 1978 see p. 279f.). 

Myrcene with its conjugated diene system readily undergoes Diels-Alder reactions with a number of dienophiles. For example, reaction with 3-meth.5i-3-pentene-2-one with a catalytic amount of AlCl gives an intermediate monocyclic ketone, which when cyclized with 85% phosphoric acid produces the bicycHc ketone known as Iso E Super [54464-57-2] (49). The product is useful in providing sandalwood-like and cedarwood-like fragrance ingredients (91). 

Reaction of 2-methoxytetrahydropyrrole with dioxalane-2,4-dione in presence of Et3N in benzene followed by treatment with MeONa in methanol afforded the monocyclic intermediate 185. Its treatment with BuLi followed by perfluorobenzoyl chloride gave 186 whose hydrolysis gave 187 which possess low or no antibacterial activity (96PHA805). Regiospecific intramolecular cyclization of 188 with sodium hydride yielded 189 as ester whose hydrolysis gave the respective acid (87JHC1537) (Scheme 35). 

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