Diastereoselective complexation

Yamamoto reported an aluminum complex-catalyzed asymmetric hetero Diels-Alder reaction (Scheme 9.19) [36]. Chiral ketone d-3-bromocamphor discriminates (R)-organoaluminum complex 34 from (S)-complex 34 by diastereoselective complexation, whereas the remaining (S)-isomer 34 catalyzes the enantioselective cycloaddition of an activated diene to benzaldehyde. 

Diastereoselective complexation of the latter cases (144a) proceeded with only modest selectivity for the former cases (144b) selectivity varied with solvent and temperatnre. The best case (dr, 97 3) ntilized a matched enantiopnre allyl tosylate with a menthyl ester anxiliary. Finally, in a few cases the addition of HFe(CO)3(NO) across diene has also proved snccesshil in the synthesis of (143). ... 

A number of enantiomerically pure complexes have been made, and this chemistry has been used in several natural product syntheses. Enantiopure complexes are readily available from the corresponding vinylic epoxides, and in cases where diastereoselective complexation is possible, diastereoselectivities tend to be moderate (typically 3 1 -4 1). The rationale for the origin of this diastereoselectivity has been proposed to derive from a preferential complexation of a Fe(CO)4 fragment to the alkene anti to the epoxide. Since the initial vinyl epoxide is conformationally flexible, four diastereomeric itt-complexes would be produced as a consequence of anti or syn complexation to the s-trans or s-cis conformers. Isomerization of these initial 7r-complexes to alkoxy- 7r-allyl species would then enable interception of an iron-bound carbonyl ligand by the alkoxide to afford diastereomeric lactone complexes. Fortunately, equilibria between the two possible trans itt-allyl complexes and their more stable cis Tr-aUyl analogs simplifies the outcome significantly. Thus, for trans vinyl epoxides, the major diastereomer typically is the one designated as endo cis (the C-1 substituent points toward the iron atom) the minor diastereomer corresponds to the exo cis isomer (the C-1 substituent points away from the iron atom) (Scheme 51). For cis vinyl epoxides, this outcome is reversed - the exo cis isomer is the major product. 

Chiral auxiliaries may also be used to effect diastereoselective complexations of acyclic dienes. For chiral dienamides (225a-d), the best case employed the sterically demanding (5 )-2-(diphenylhydroxymethyl)pyrrolidine auxiliary. Diene (225d) was complexed with excellent diastereoselectivity but in modest yield (Scheme 64). For substrates (217a-c), diastereomer ratios of the corresponding complexes were poorer (1.5 1 to 4.6 1), likely a result of the increased distance between the auxiliary s chiral center and the diene. 

As with acyclic dienes, methods have been developed for enantioselective and diastereoselective complexation of prochiral and chiral cyclic dienes. An approach has been developed for the asymmetric catalytic complexation of prochiral eyelohexa-1,3-dienes nsing (1) in the presence of catalytic amounts of l-azabuta-l,3-dienes such as (232) or (233) an enantiomeric excess as high as 86% has been reported. By contrast, attempts to effect diastereoselective complexations using cyclic diene systems eqnipped with chiral auxiliaries have met with limited success. On the other hand, direct complexation of chiral cyclic dienes snch as (234) and (235) proceed with a high degree of diastereoselectivity, where the iron tricarbonyl fragment is directed syn to alcohols or ethers by transient coordination ( heteroatom dehvery ) (Scheme 66). ... 

Diastereoselective complexations affording chiral heterodiene complexes are also known (Scheme 74) 374-376 complexation of the enantiomerically pure iV-benzyl vinylim-ines was shown to proceed under kinetic control equilibration to thermodynamic mixtures possessing poorer diastereomer ratios occurred upon standing. On the other hand, the diastereoselective complexation of an enantiomerically pure enone with a side chain possessing chirality and a chelating phosphite group was shown to proceed under thermodynamic control (Scheme 75). The product (a single diastereomer was formed) could be transformed by nucleophihc addition at the -position. 

This synthesis is remarkable because mayor parts of it are carried out at the Cr(CO)3-complexed ligand and several new bonds are formed with high diaster-eoselectivity under the stereochemical influence of the planar-chiral n-complex moiety. The chiral building block 80 is obtained in enantiomerically pure form either by resolution (via imine formation with 1-valinol) or by diastereoselective complexation of a chiral cyclic aminal according to the procedure of Alexakis... 

Diastereoselective complexation of a chiral [antagonist] ketone with a racemic aluminium Lewis acid catalyst effectively removes one enantiomer of the latter, leaving the uncomplexed antipode free to function as a chiral Lewis acid. E Asym. heterodiene synthesis. 0.1 eq. D-3-bromocamphor, 1.05 eqs. startg. siloxydiene, and benzaldehyde added sequentially to 0.1 eq. of the racemic aluminium complex in degassed methylene chloride at —78°, stirred for 3 h, then subjected to acidic work-up (2S,3S)-product. Y 78% (e.e. 82%, upgraded to > 98% by one recrystallization with ca. 60% recovery). F.e.s. K. Maruoka, H. Yamamoto, J. Am. Chem. Soc. Ill, 789-90 (1989). 

A foldamer-based molecular recognition system that has enantiomeric M and P helical conformation was also studied. The diastereoselective complexation of an achiral, amphiphilic, helical m-phenylene ethynylene dodecamer 13 with a chiral plant natural product a-pinene 14 was demonstrated by ICD studies (Figure 10). The stoichiometry of the complex was determined as 1 1 by CD titration measurements based on the linearity of a Benesi-Hildebrand plot and the slope of a Hill plot. The association constant was estimated to be = 6.83 x 10" indicating that 13 can capture 14 efficiently. The results suggested that the chiral guest can stabilize one of the oligomer s enantiomeric helical M or P conformations. 

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