Stericaliy Congested Molecules: 2,2′‐[(Biaryldiyl)bis(oxy)]bis[1,3,2‐oxazaphospholidines]
Authors: Pastor Stephen D. , Rodebaugh R. K. , Odorisio Paul A. , Pugin Benoit , Rihs Grety , Togni Antonio 
Published: December 2004

The original suggestion that a through‐space mechanism was operative in the seven‐bond J(P, P) coupling constant of 30.3 Hz observed for 3.3′‐bis(1,1‐dimethylethyl)‐2,2′‐[3,3′,5,5′‐tetrakis(1,1‐dimethylethyl)‐1,1′‐biphenyl‐2,2′‐diyl]bis(oxy)}bis[1,3,2‐oxazaphospholidine] (1a)) was investigated. In the solid‐state CP‐MAS 31PNMR spectrum of 1a, two nonequivalent P‐atoms were observed; sufficient resolution could not be obtained to determine whether P, P coupling was present. The preparation and spectral data of the N‐methyl analogue 1b and of the acyclic N‐isopropyl analogue 6 (Scheme 1) provided evidence that a) the essentially exclusive formation (R*, R*,S*)‐1ain the reaction of the disodium biphenyldiolate 3a with the phosphorochloridite 4a is the result of significant differences in the free energy of activation (ΔG*) for the formation of the various diastereoisomers due to the steric congestion within the molecule and that b) the magnitude of the observed P,P coupling is dependent upon the degree of conformational freedom within the molecule. In the 31P‐NMR spectrum of the P‐sulfide 7, which was prepared by the reaction of la with sulfur, 2s resonances were observed that strongly suggested that the lone electrons pair on P are involved in the mechanism for the transmission of coupling data. The (4S,5R)‐12 and (4R, 5S)‐12 of la were prepared in a three‐step reaction sequence starting from the corresponding enantiomerically pure norephredine 8 (Scheme 2). Both (4S, 5R)‐ and (4R, 5S)‐12 were obtained as a diastereoisomer mixture that differ by the configuration of the axis of chirality, i.e., (R*R*,R*)‐ and (R*,S*,R*)‐12 were obtained. The major diastereoisomer was obtained upon recrystallization, and the atropisomers were observed to equilibrate in solution by monitoring the HC(5) resonance in the 1H‐NMR with time (ΔG° = 0.4 kcal/mol; Fig. 2). The process observed corresponds to the restricted rotation about the central single bond of the biphenyl system. The isolation of an atropisomer with only a single ortho substituent on each aryl ring is quite rare. In the 13C‐NMR spectrum of both (R*,R*,R*)‐ and (R*,S*,R*)‐12, C(5) is two‐bond‐coupled to the oxazaphospholidine P‐atom (2J(C(5),P((2)) = 8.5 Hz) that is further virtually coupled to the P‐atom of the other oxazaphospholidine ring (7J(P(2),P(2′)) = 30 Hz; 9J(C(5),P(2′)) = 0 Hz; δ(P(2)) = δ(P(2′)) = 136 ppm. In the 31P‐NMR spectrum of (R*,R*,S*)‐12, which was prepared from the racemic chloridite (mixture of three diastereoisomers was obtained), a 7J(P(2),P(2′) of 36 Hz was observed. These observations provide strong evidence that seven‐bond P,P coupling occurs in all three diastereoisomers of 12. The observed P,P coupling is both independent of the configuration of the chiral axis and the configuration of the asymmetric P‐centers. This independence of P,P coupling upon the configuration on P implies also the independence of the observed coupling upon the orientation of the lone‐pair of electrons on P provided that the conformations of the diastereoisomers are similar in solution. The X‐ray crystal structure of the complex formed from 1a and dichloro(cycloocta‐1,5‐diene)platinum(II) was obtained and the solid‐state structure discussed. The major diastereoisomer of (4S,5R)‐12 was used as a chiral ligand in asymmetric hydrosilylation and hydrogenation reactions (Scheme 3).