Ring systems endo reactions

In intramolecular Diels-Alder reactions, two rings are formed in one step. The reaction has been used to synthesize a number of interesting ring systems.29 The intramolecular cyclization of ( )-l-nitrodeca-l,6,8-triene at 80 °C affords an endo cycloadduct with the tram ring fusion preferentially, as shown in Eq. 8.18. In contrast, (Z)-nitroalkenes produce a nearly 1 1 mixture of cis- and tra/w-fused cycloadducts.30... 

There are also many examples of alkylation reactions involving the norbornyl ring system in which the enolate can be either endo- or c.vo-cyclic. Both the endo-cyclic (6, 7) and evo-cyclic (8) enolates exhibit high levels of asymmetric induction due to the rigid ring system. Scheme 2-8 presents some examples for alkylation involving the norbornyl ring system.15... 

The reactions of 1,2,3-triazolium 1-imide (277) with a range of alkene and alkyne dipolarophiles give rise to a variety of new ring systems (Scheme 54). Compounds (276) and (278) are obtained from (277) by reaction with acrylonitrile and DMAD, respectively. These reactions are tandem 1,3-dipolar (endo) cycloadditions and sigmatropic rearrangements which are regio- and stereospecific <90JCS(Pl)2537>. Kinetic and mechanistic studies show that these reactions are dipole-HOMO controlled. The second-order rate constants are insensitive to solvent polarity, the reaction indicates... 

Among the isohexides, isosorbide (3) has two hydroxyl groups and these are in different steric surroundings that is, the OH-2 group in the exo and the OH-5 group in the endo position of the bicyclic ring-system. Many attempts have been made to control the regioselectivity of reactions at these positions. 

Systems which can react by either 5-exo or 6-endo cyclization normally produce the five-membered ring system. Exceptions result when equilibration of the initially formed five-membered ring is facile and substitution electronically favors the 6-endo mode of cyclization. Several examples have been found in amidoselenation reactions.41158 216 216 232 For example, halocyclization of thioimidate (17) produced only the pyrrolidone product,217b 217c 233 while selenocyclization of amide (18) produced only the piperi-done product.232 Note that the cyclization of (18) to a piperidone also involves regioselectivity in the cyclization of an amide functionality to a lactam rather than an imidate. Both the ring size and type of product can be explained by equilibration. 

A stereoselective 6-exo selenoamination to form a tetrahydroisoquinoline ring system is probably a result of the specific substitution pattern.252 Selenocyclizations which generate piperidine systems by 6-endo cyclization give products predicted by reaction through the more stable chair conformation (equation 116).41 158c 216e,232a... 

As for the biaryl ether containing macrocycles, an array of bioactive macrocycles with an endo aryl-aryl bond exist in nature. A new palladium catalyzed reaction has been recently developed in which bis(pinacolato)diborane(4) mediated the process to reach such a structural motif. The reaction consists of a domino process involving a Miyaura s arylboronic ester synthesis and an intramolecular Suzuki-coupling. Synthesis of a bicyclic A-B-O-C ring system of RP-66453 273, a neurotensine receptor antagonist, with an endo aryl-aryl and an endo aryl-aryl ether bond was described (Scheme 53).141... 

More complex ring systems have been built up using the CuOTf-catalyzed [2 + 2] photocydoaddition. For instance, transformation of the cydopentene derivative 21 leads in high yields to the tricyclic compounds 22a,b (Scheme 5.5, reaction 9) [27], with the endo isomer 22a being obtained in excess. The reaction was applied to... 

Maleic anhydride reacts with cyclopenta-1,3-diene in a Diels-Alder reaction. Since there is a plane of symmetry, the reaction can lead to two achiral compounds, which are diastereomers of each other, containing an endo- or exo-oriented dicarboxylic anhydride group. These differ in absolute and relative configuration at the bond shared by both rings. Under normal conditions the Diels-Alder reaction proceeds stereospecifically to yield preferentially the endo product. Note that in the tricyclic product no trans fusion in the ring system is possible as a consequence of the reaction mechanism. Subsequent reduction of the products therefore affords two diols, which are also diastereomers of each other. These may be separated by chromatography on an achiral stationary phase. 

The influence of secondary overlap was first observed in reactions using cyclopen-tadiene to form bicyclic ring systems. In the bicyclic product (called norbornene), the electron-withdrawing substituent occupies the stereochemical position closest to the central atoms of the diene. This position is called the endo position because the substituent seems to be inside the pocket formed by the six-membered ring of norbornene. This stereochemical preference for the electron-withdrawing substituent to appear in the endo position is called the endo rule. 

Two sequential electrochemical annulations of an electron-rich 3,4-disubstituted furan ring were employed to generate the fused tricyclic ring system of arteannuins. The second reaction, as depicted below, represented the formation of a quaternary carbon center by a formal 6-endo cyclization under these anodic oxidation conditions <07OL4599>. 

Presumably, isomer 931 arises via reaction of the allylic radical 930 with Bu3SnH. No product of cyclization to C-3 of the pyrrole (6-endo) was detected indicating a preference for radical addition to C-2. Cyclization of pyrroles 933, in which the linking chain is attached to C-3 of the pyrrole ring, gave exclusively the rearomatized (y-endo cyclization product 935 via the intermediate radical 934 (Scheme 182). This cyclization proceeds in moderate yield to give a novel pyrroloquinolone ring system. 

In an asymmetric approach to the bicyclo[2.2.2]octane ring system, a double Michael addition has been employed using phenylmenthyl acrylate as the initial Michael acceptor. The condensation of the dienolate, generated with Lithium Diisopropylamide, reacts with the acrylate to afford the bicyclo[2.2.2]octane derivative (eq 6). The de for the reaction is only 50% however, it is highly endo selective (>95%). ... 

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