X-RAY AND H-1-NMR STUDIES OF THE CONFORMATIONAL EQUILIBRIA OF 2-Z-3-PHENYL-1,3,2-OXAZAPHOSPHORINANES - STERIC AND STEREOELECTRONIC INFLUENCES ON THE UNEXPECTED AXIAL PREFERENCES OF ME2N AND MENH SUBSTITUENTS ON 3-COORDINATE PHOSPHORUS

A series of 2-Z-3-phenyl-1,3,2-oxazaphosphorinanes 7-14 (Z = MeO, (CF3 )2CHO, Ph, MeNH, and Me2N) containing three-coordinate phosphorus was prepared. The conformations of the six-membered rings were investigate d by H-1 and P-31 NMR spectroscopy and X-ray crystallography. The ring s with substituents MeO, (CF3)2CHO, Ph, and MeNH on phosphorus can be unambiguously assigned in solution to a single chair conformation with the substituent of phosphorus axial. An X-ray crystal structure of ,5 -dimethyl-2,3-diphenyl-1,3,2-oxazaphosphorinane, 11, reveals a chair f orm ring with the phenyl group attached axially to phosphorus. For 13 and 14 with a Me2N substituent on phosphorus, a chair-chair equilibriu m (20 reversible 21) is found in solution that features an 80-90% popu lation (DELTAG-degrees = 0.9-1.1 kcal/mol) of the Me2N axial conformat ion (20). This finding contrasts sharply with the known 1 kcal/mol pre ference for the Me2N to be equatorial in the corresponding 2-(dimethyl amino)-1,3,2-dioxaphosphorinanes. The ability of the 1,3,2-oxazaphosph orinane ring to accommodate the Me2N substituent axially is also seen in the X-ray crystal of phenyl-2-(dimethylamino)-1,3,2-oxazaphosphorin ane, 13, which features a chair conformation ring that is considerably distorted compared to that of 11, quite evidently to allow the Me2N t o be in the observed axial orientation, conformation 20. It is argued that the axial orientation of the Me2N in 13 and 14 is at least partly in response to steric repulsions in the alternative chair conformatio n 21 between the equatorial Me2N and the phenyl substituent at N(3). T his effect is in direct contrast to the repulsive interactions between the N(3)Ph and axial Me2N on phosphorus previously demonstrated for f our-coordinate, 2-oxo-1,3,2-oxazaphosphorinanes. The increased bond le ngths within the 1,3,2-oxazaphosphorinane ring over its 1,3,2-dioxapho sphorinane counterpart (C-N vs C-O) and increased ring flexibility, al ong with potential n --> sigma stereoelectronic factors of the type o perative in the anomeric effect, are also proposed as potential contri butors to the preferred axial orientation of Me2N in 13 and 14. The di astereomeric molecules cis- and phenyl-2-(dimethylamino)-1,3,2-oxazaph osphorinane, 17, also were prepared. At thermodynamic equilibrium at r oom temperature, cis-17 (2-Me2N and 5-t-Bu groups cis) is favored (cis /trans = 80/20). cis-17 displays a conformational equilibrium (Scheme 1) involving a chair conformer (almost-equal-to 60%) with the t-Bu equ atorial and Me2N axial, cis-17a, and a single twist or boat form with both substituents pseudoequatorial, cis-17d (almost-equal-to 40%). tra ns-17 exists in solution in three conformations in approximately equal populations: a chair form with both t-Bu and Me2N equatorial (trans-1 7a) and two boat/twist forms (trans-17b and trans-17c) with the t-Bu p seudoequatorial and the Me2N pseudoaxial. The distributions of chair a nd boat/twist conformations can be reasonably understood in terms of t he same 1,3-syn axial and vicinal PhN-(3)/Me2N(eq) steric repulsions i nvoked to explain the chair-chair equilibria noted for the unsubstitut ed and (dimethylamino)-3-phenyl-1,3,2-oxazaphosphorinanes 13 and 14. T he free energy difference between chair and boat/twist forms evidently is very small.