Further Characterization of Mitsunobu-Type Intermediates in the Reaction of Dialkyl Azodicarboxylates with P(III) Compounds

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)](ArCO2-) [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.