Intramolecular bisamidation

Consider the divergent synthesis of PAMAM dendrimers, 76 whereby undesired intra-or inter-molecular events lead to increased polydispersity and lost ideality. Although these events can be minimized or in selected cases eliminated, interestingly these processes can give rise to randomly positioned polydendritic systems. Thus, amidation of polyesters (e.g., 1) with a diamine can lead to intramolecular bisamidation which can give rise to topological dendrimer connection (Scheme 9.1) as depicted by catenated bisdendri-... 

A basically new type of synthesis of dihydrooxazines was applied for the preparation of 177 and 179 (86JOC3248). Boron trifluoride catalyzed the intramolecular [4+2] cycloaddition of the A-acyliminium compounds derived from 176 and 178, resulting stereospecifically in the rrani-fused cyclo-pent[d][l,3]oxazines and partly saturated 3,1-benzoxazines 177 and 179, respectively. The steric orientation of the 4-methyl substituent of the product is controlled by the Z and geometry of the starting bisamides 176 and 178 (86JOC3248). 

Alternatively, the remaining sulfate ester of 70 may serve as a leaving group for a second nucleophilic displacement reaction. When this displacement is by an intramolecular nucleophile, a new ring is formed, as was first shown in the synthesis of a cyclopropane with malonate as the nucleophile [68] and of aziridines with amines as the nucleophiles [76]. The concept is further illustrated in the double displacement on (/J,/ )-stilbenediol cyclic sulfate (72) by benzamidine (73) to produce the chiral imidazoline 74 [79]. Conversion of the imidazoline (74) to (.V,.S )-stilbenediaminc 75 demonstrates an alternative route to optically active 1,2-diamines. Acylation of 75 with chloroacetyl chloride forms a bisamide, which, after reduction with diborane, is cyclized to the enantiomerically pure trans-2,3-diphenyl- 1,4-diazabicy-clo[2.2.2]octane (76) [81],... 

The multicomponent LJgi reaction was successfully applied to the synthesis of bisamides 56, which on deprotection, followed by carbonylation and intramolecular amidation, afforded the macrolactams, 1,4-diazocines 57, as racemic mixtures (Scheme 7) <2005TL1697>. 

Weinreb et al. have systematically explored the intramolecular Diels-Alder reaction of N-acyl-imines generated from the bisamides (79) to extend the usefulness of this little studied reaction. 

These intramolecular hydroaminations lead to the formation of chiral products. Thus, several studies have been devoted to developing ligands for enantioselective, intramolecular hydroaminations of olefins catalyzed by lanthanide complexes. ° Selectivities of these reactions with chiral cyclopentadienyl derivatives have been modest. Selectivities have been higher with catalysts containing non-cyclopentadienyl ligands. Some of tlie most selective catalysts are the yttrium complexes of the bis(thiolate) ligands reported by Livinghouse, the scandium and lutetium complexes of 33 -disubstituted binaphtholates reported by Hultzsch, and the BINAM-based bisamidates of Schafer.- A representative cyclization catalyzed by a member of each of these classes of catalyst are shown in Equation 16.64. 

However, some cases are known in which electronic effects of substituents strongly influence the outcome of the intramolecular Heck reaction. The example presented in Scheme 3 is especially illustrative the bisamide underwent a monocyclization to give a highly substituted indole, whereas the corresponding dimethoxy-substituted starting material did not react at aU. ... 

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