Cyclization medium-sized cyclizations

RCM of 132 to the medium-sized enyne 135, for example, appears to be highly unlikely. This transformation was achieved by conversion of 132 to the cobalt complex 133, which is cyclized to the protected cycloenyne 134. Deprotection yields 135, and a subsequent Pauson-Khand reaction yields the interesting tricyclic structure 136 (Scheme 27) [125c]. 

A well-known characteristic of medium-sized rings (8- to 11-membered) is their ability to undergo facile transannular reactions. Cere et al. found that acid-catalyzed transannular cyclizations of 8-10-membered 7,5-unsaturated cyclic sulfides yield fused bicyclic sulfonium salts independently of the geometry of the double bond <1998J(P2)977>. 

Tanaka and Ohno developed the palladium(0)-catalyzed cyclization of bromoallene 222 bearing a sulfonamide for the synthesis of medium-sized heterocycle 223 (Scheme 37).48b In this reaction, bromoallene acts as an allyl dication equivalent 224, and two different nucleophiles can be introduced regioselectively. The intramolecular nucleophilic... 

High oxidation state alkylidene complexes in which a heteroatom is bound to the alkylidene carbon atom are extremely rare [41]. Since the approach shown in Eq. 43 failed, the related approach shown in Eq. 44 was taken to prepare the medium-sized ring subunits [222]. The latter product was formed in good yield when n=2, R H, R2=Et, but only poor yield when n=2, R =Et, R2=H, possibly due to unfavorable interactions between the ethyl substituent and transannular groups in the transition state for cyclization of the allyl ether [222]. Ruthenium catalysts either failed or gave low yields, presumably because of the steric hindrance associated with ring-closing dienes of this type. 

Successful applications of RCM to the formation of almost any ring size 5 have been reported in the literature, including medium-sized and macrocyclic compounds. While the synthesis of 5-, 6- and 7-membered rings is rather general [3] (for representative examples see Table 3) and only few failures have been recorded, unfavorable conformational effects and/or strain in the molecule may render the cyclization of larger rings significantly more delicate. Therefore it is appropriate to discuss the present state of the art in this particular field in some detail. 

Medium-ring acetylenic lactones,2 Cyclization to medium size acetylenic lactones is difficult because of geometric constraint imposed by the triple bond, and has been considered practicable only for at least fifteen-membered rings. Surprisingly, the acetylenic w-hydroxy acid 1 when complexed with Co2(CO), is cyclized in 28% yield to the seven-membered complexed acetylenic lactone 2 by Mukai-yama s reagent, 2-chloro-l-methylpyridinium chloride (8, 95-96). The yield is essentially the same as that observed in lactonizaton to a complexed 10-membered... 

Several biologically useful medium-sized benzo-fused heterocycles have been efficiently constructed by combining the efficiency of the Ugi condensation with a post-condensation S Ar cyclization, using an internal amino or hydroxyl nucleophile, and a nitrohalobenzoic acid 63 (Fig. 16). By introducing the additional nucleophile into the amine component, benzodiazepinones 79 [72], benzodiazoci-nones 80 [72], their benzo-fused counterparts 81 [72], benzoxazepinones 82 [72] and their fused counterparts 84 [60] and finally benzoxazocinones 83 [72] have been obtained. For the first two systems, the already described UDC strategy was exploited, whereas for the oxa heterocycles, the alcoholic or phenolic hydroxyl did... 

Starting from complex IX, Fiirstner developed a homobimetallic phenylindeny-lidene complex XXV (Equation 8.5), and both of these were used in the cyclization of medium-sized rings by RCM. A series of examples is presented which shows that indenylidene complexes are as good as or superior to the classical Grubbs first generation catalyst in terms of yield, reaction rate, and tolerance towards different functional groups (Scheme 8.17) [58]. 

Azacyclanones,2 The usual syntheses of medium-sized azacyclanones involve Dicckmann or acyloin cyclization conducted under high dilution. An interesting new approach involves hydroboration-cyanidation (4, 446-447 5, 606-607) of a diunsaturated carbamate such as 1. llydroboration of I with thexylboranc followed by cyanidation under standard conditions gives the cyclic ketone 2 in moderate yield in one step. The product can be rcductivcly cyclizcd to the indoliz.idinc alkaloid 5-coniceine (3). 

Among the other noteworthy structural features of 1 are its central nine-membered B ring that is home to three of the four stereogenic centers. The 1,5 relationship of two carbonyls such as those positioned at C7 and C14 has traditionally fostered transannular cyclizations in medium-sized rings. Accordingly, this... 

An equivalent reaction has been achieved via the treatment of hydroborated bisalkenes with alkaline silver nitrate solution (Table 1.4).22,23 This method has been used to synthesize a number of small and medium-size carbocyclic rings in moderate to good yield. The selectivity for terminal cyclization observed for 1,6-heptadiene and 1,7-octadiene indicates that, in these cases, hydroboration of each of the alkenes occurs independently to yield acyclic boranes. It has, however, been found that both cyclic and acyclic boranes react under these conditions to yield the ring-closed products (Scheme 1.3). 

Marco-Contelles and de Opazo utilised 8-ewd< -trig and 1-exo-Aig cyclizations, mediated by B113S11H, in their construction of chiral, polyfunctionalised medium-sized carbo-cycles670. For example, treatment of iodide (104) with BujSnll under standard radical conditions afforded 7-membered carbocycles (105) in moderate yield (equation 79). Prado and coworkers reported the synthesis of benzolactams by 11 -endo aryl radical cyclization, an example of which is highlighted in equation 80675. 

In this connection, transannular cyclization reactions between the ketonic carbonyl group and the amino nitrogen atom in medium-sized rings are of great interest. Cryptopine (10) is the most usual example, but not the best investigated case, of this kind. The appropriate inter-... 

CYCLIZATION TO MEDIUM-SIZED AND LARGE-SIZED RINGS... 

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