Further characterization of Mitsunobu-type intermediates in the reaction of dialkyl azodicarboxylates with P(III) compounds

Abstract

Structural characterization of compounds analogous to the proposed intermediates in the Mitsunobu esterification process is achieved by the combined use of NMR spectroscopy and X-ray diffractometric studies. The results show that compounds (t-BuNH)P(μ-N-t-Bu)₂P[(N-t-Bu)(N-(CO₂R)-N(H)(CO₂R))] [R = Et (11), i-Pr (12)], obtained by treating [(t-Bu-NH)P-μ-N-t-Bu]₂ (10) with diethylazodicarboxylate (DEAD) or diisopropylazodicarboxylate (DIAD), respectively, have a structure with the NH proton residing between the two nitrogen atoms ((P)N(t-Bu) and (P)N-N(CO₂Et)); this is the tautomeric form of the expected betaine (t-BuNH)P(μ-N-t-Bu)₂P⁺[(NH-t-Bu)(N-(CO₂R)-N-(CO₂R)]. Treatment of ClP(μ-N-t-Bu)₂P[(N-t-Bu){N-(CO₂-i-Pr)-N(H)(CO₂-i-Pr)] (6) with 2,6-dicholorophenol affords (2,6-Cl₂-C₆H₃-O)P(μ-N-t-Bu)₂P⁺[(NH-t-Bu){N[(CO₂i-Pr)(HNCO₂i-Pr)]}](Cl^-)(2,6-Cl₂-C₆H₃-OH) (14) that has a structure similar to that of (CF₃CH₂O)P(μ-N-t-Bu)₂P⁺[(NH-t-Bu){N[(CO₂i-Pr)(HNCO₂i-Pr)]}](Cl^-) (13), but with an additional hydrogen bonded phenol. Both of these have the protonated betaine structure analogous to that of Ph₃P⁺N(CO₂R)NH(CO₂R)(R'CO₂)- (2) proposed in the Mitsunobu esterification. Two other compounds, (ArO)P(μ-N-t-Bu)₂P⁺(NH-t-Bu){N(CO₂i-Pr)(HNCO₂i-Pr)}(Cl-) [Ar = 2,6-Me₂C₆H₃O- (15) and 2-Me-6-t-Bu-C₆H₃-O- (16)], are also prepared by the same route. Although NMR tube reactions of 11 or 12 with tetrachlorocatechol, catechol, 2,2'-biphenol, and phenol revealed significant changes in the ³¹P NMR spectra, attempted isolation of these products was not successful. On the basis of ³¹P NMR spectra, the phosphonium salt structure (t-BuNH)P(μ-N-t-Bu)₂P⁺[(HN-t-Bu){N-(CO₂R)-N(H)(CO₂R)](ArO-) is proposed for these. The weakly acidic propan-2-ol or water did not react with 11 or 12. Treatment of 12 with carboxylic acids/ p-toluenesulfonic acid gave the products (t-BuNH)P(μ-N-t-Bu)₂P⁺[(HN-t-Bu){N-(CO₂-i-Pr)-N(H)(CO₂-i-Pr)](ArCO^2-) [Ar = Ph (18), 4-Cl-C₆H₄CH₂ (19), 4-Br-C₆H₄ (20), 4-NO₂-C₆H₄ (21)] and (t-BuNH)P(μ-N-t-Bu)2P⁺[(HN-t-Bu){N-(CO₂-i-Pr)-N(H)(CO₂-i-Pr)](4-CH₃-C₆H₄SO₃^-) (22) that have essentially the same structure as 2. Compound 18 has additional stabilization by hydrogen bonding, as revealed by X-ray structure determination. Finally it is shown that the in situ generated (t-BuNH)P(μ-N-t-Bu)₂P⁺[(HN-t-Bu){N-(CO₂Et)-N(H)(CO₂Et)](4-NO₂-C₆H₄CO₂^-) can also effect Mitsunobu esterification. A comparison of the Ph₃P-DIAD system with the analogous synthetically useful Ph₃P-dimethyl acetylenedicarboxylate (DMAD) system is made.