Conformational control of flexible molecules: design and synthesis of novel chiral 1,5-diaza-cis-decalins.
Control of the conformational equilibria of 1,5-diaza-cis-decalins, a new class of chiral diamine ligands, has been investigated. Chiral 2,6- and 3,7-substituted derivatives of 1,5-diaza-cis-decalins were designed to stabilize the conformational form needed to chelate a lithium. These derivatives were synthesized in optically pure form starting from 1,5-diaza-cis-decalin. Due to the rigid and conformationally well-defined nature of these compounds, the potential of these compounds as chiral diamine ligands was investigated. Asymmetric lithiation-substitution reactions of N-Boc-pyrrolidine and N,N-diisopropyl-o-ethylbenzamide were performed using these ligands and up to 60% ee was obtained. For the latter substrate, results spanning a range from 32% ee (R) to 60% ee (S) were obtained (Delta ee = 92%) with 1,5-diaza-cis-decalin ligands differing only in the location of two methyl substituents. Unlike many other diamines that have been employed in asymmetric lithiation-substitution reactions, the limited conformational flexibility of the 1,5-diaza-cis-decalins is analogous to (-)-sparteine such that these results may permit the construction of structure-activity relationships.
Xu
Zhenrong
Z
Department of Chemistry, Roy and Diana Vagelos Laboratories, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Kozlowski
Marisa C
MC
D001372:Aza Compounds / Q000737:chemistry*; D002384:Catalysis; D006574:Heterocyclic Compounds, 2-Ring / Q000737:chemistry*; D008024:Ligands; D008094:Lithium / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry; D013034:Sparteine / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C430116:1,5-diazadecalin; D001372:Aza Compounds; D006574:Heterocyclic Compounds, 2-Ring; D008024:Ligands; D010880:Piperidines; D011759:Pyrrolidines; D013034:Sparteine; D008094:Lithium