Observation of Pseudorotamers of Two Unconstrained Wittig Intermediates, (3RS,4SR)- and (3RS,4RS)-4-Cyclohexyl-2-ethyl-3,4- dimethyl-2,2-diphenyl-1,2λ⁵-oxaphosphetane, by Dynamic ³¹P NMR Spectroscopy:  Line-Shape Analyses, Conformations, and Decomposition Kinetics

Abstract

The two typical, that is unstabilized and unconstrained, oxaphosphetane diastereomers (3RS,4SR)- (3) and (3RS,4RS)-4-cyclohexyl-2-ethyl-3,4-dimethyl-2,2-diphenyl-1,2λ5-oxaphosphetane (5) have been prepared selectively by deprotonation of (1RS,2SR)- (6) and (1RS,2RS)-(2-cyclohexyl-2-hydroxy-1-methylpropyl)ethyldiphenylphosphonium iodide (7). The X-ray structure analysis of 7 established the relative configurations of 6 and 7 and consequently those of 3 and 5. Pseudorotation of the 1,2-oxaphosphetanes 3 and 5 and their alkene formations have been studied by 31P NMR spectroscopy. The conformations of the resolved pseudorotamers at the pentacoordinate trigonal bipyramidal phosphorus atom are identified by 1H, 13C, and 31P NMR data. For both diastereomers, the two rotamers with equatorial position of the ethyl substituent dominate in pseudorotation. Line-shape analyses provided the rate constants and activation parameters of pseudorotations. The results represent the first experimental data for pseudorotation of unstabilized and unconstrained 1,2-oxaphosphetanes. Oxaphosphetanes 3 and 5 stereoselectively decompose to (Z)- and (E)-2-cyclohexylbut-2-ene, respectively. At −30 °C, pseudorotations are faster than alkene formations by a factor of ca. 1011, and at −20 °C, the half-life of the trans isomer 5 in alkene formation is approximately 8 times longer than that of the cis isomer 3.

The modern interpretation of the Wittig reaction mechanism

“…42 Calculations on the reactions of M eCHO with Ph 3 P=CHM e and M e 3 P=CHM e respectively show that betaines are 25 significantly higher in energy than OPAs and likewise TSs involving anti addition of the reactants (in the style of an aldol reaction to form an anti-betaine) are higher in energy than cycloaddition TSs. 42 The cycloaddition mechanism of Vedejs for the Li-salt free 30 Wittig reaction of non-stabilised ylides -that being direct, irreversible cycloaddition of ylide and aldehyde to give OPA, followed by facile pseudorotation of the OPA and then by irreversible, stereospecific [2+2] cycloreversion of OPA to alkene and phosphine oxide -is consistent with the following facts: 35 -OPA formation has been shown to be irreversible, 68,69,93 and the OPA cis/trans ratio corresponds to the Z/E ratio of the alkene ultimately obtained from the reaction. 68,69,93 This implies that the stereoselectivity is determined in the OPA forming step.…”

“…42 The cycloaddition mechanism of Vedejs for the Li-salt free 30 Wittig reaction of non-stabilised ylides -that being direct, irreversible cycloaddition of ylide and aldehyde to give OPA, followed by facile pseudorotation of the OPA and then by irreversible, stereospecific [2+2] cycloreversion of OPA to alkene and phosphine oxide -is consistent with the following facts: 35 -OPA formation has been shown to be irreversible, 68,69,93 and the OPA cis/trans ratio corresponds to the Z/E ratio of the alkene ultimately obtained from the reaction. 68,69,93 This implies that the stereoselectivity is determined in the OPA forming step. OPA decomposition has been shown to occur 40 at the same rate as alkene formation for reactions of alkylidenetriphenylphosphoranes.…”

“…That is, erythro -HPS gave only cis-OPA and hence only Z-alkene, and likewise threo -HPS gave trans-OPA and hence E-alkene. 68,69,93 Other examples exist in which the β-HPS deprotonation technique has been used to demonstrate the operation of kinetic control in Wittig reactions of 45 non-stabilised ylides. 94 Another method for OPA generation independent of a Wittig reaction involves S N 2 epoxide ring-opening by lithium diphenylphosphide to give β-oxidophosphine, which is quaternised with methyl iodide to give betaine and hence OPA.…”

“…93 20 In the studies of Vedejs and M arth 74,90 and Bangerter et. al., 93 the rate of pseudorotation of each OPA was established by line shape analysis of variable temperature NM R spectra of the resolved OPA pseudorotamers. It was concluded that in each case the rate of OPA pseudorotation is too fast relative to the rate 25 of OPA decomposition to have any effect on the decomposition rate.…”

“…al. 93 concluded that in the case of each of the OPAs 19/20, 21a/22a and 21b/22b, one of the two possible pseudorotamers is predominant in solution, and that the pseudorotamers do not interconvert rapidly at low temperature. (ii) S electivity in reactions of non-stabilised ylides By the convention employed in the paper of Aggarwal, Harvey 5 and coworkers, 42 when the ylide P=C bond and the aldehyde C=O bond are parallel (i.e.…”