Diverse Modes of Reactivity of Dialkyl Azodicarboxylates with P(III) Compounds:  Synthesis, Structure, and Reactivity of Products Other than the Morrison−Brunn−Huisgen Intermediate in a Mitsunobu-Type Reaction

Abstract

The reactivity of diethyl azodicarboxylate (DEAD)/diisopropyl azodicarboxylate (DIAD) with P(III) compounds bearing oxygen or nitrogen substituents is explored. Compounds with structures quite different from that of Morrison-Brunn-Huisgen intermediate R'(3)P(+)N(CO(2)R)N(-)(CO(2)R) (1), observed in the Mitsunobu reaction, have been established by using X-ray crystallography and NMR spectroscopy. Thus reactions with X(6-t-Bu-4-Me-C(6)H(2)O)(2)P-NH-t-Bu [X = S (8), CH(2) (9)] or XP(mu-N-t-Bu)(2)P-NH-t-Bu [X = Cl (14) or NH-t-Bu (15)] and DEAD/DIAD lead to phosphinimine-carbamate-type of products X[6-t-Bu-4-Me-C(6)H(2)O](2)P[N-t-Bu][N(CO(2)R)NH(CO(2)R)] [X = S, R = Et (16); X = CH(2), R = Et (17); X = CH(2), R = i-Pr (18)] or XP(mu-N-t-Bu)(2)P(N-t-Bu)[N-(CO(2)-i-Pr)-N(H)(CO(2)-i-Pr) [X = Cl (19), NH-t-Bu (20)]. Treatment of 19 with 2,2,2-trifluoroethanol afforded the product [(CF(3)CH(2)O)P(mu-N-t-Bu)(2)P(+)(NH-t-Bu)[N(CO(2)-i-Pr)(HNCO(2)-i-Pr)]][Cl(-)] (21) whose structure is close to one of the intermediates proposed in the Mitsunobu reaction. The isocyanate CH(2)(6-t-Bu-4-Me-C(6)H(2)O)(2)P-NCO (10) underwent 1,3-(P,C) cycloaddition with DEAD/DIAD to lead to CH(2)(6-t-Bu-4-Me-C(6)H(2)O)(2)P[N(CO(2)R)N(CO(2)R)-C(O)-N] [R = Et (22), i-Pr (23)]. Reaction of 22-23 with 1,1'-bi-2-naphthol or catechol leads to novel tetracoordinate CH(2)(6-t-Bu-4-Me-C(6)H(2)O)(2)P(2,2'-OC(10)H(6)-C(10)H(6)-OH)[NC(O)-(CO(2)R)NH(CO(2)R)] [R = Et (24), i-Pr (25)] or pentacoordinate CH(2)(6-t-Bu-4-Me-C(6)H(2)O)(2)P(1,2-O(2)C(6)H(4))[NHC(O)-N(CO(2)R)NH(CO(2)R)] [R = Et (26), i-Pr (27)] compounds in which the original NCO residue is retained; this mode of reactivity is quite different from that observed for the MBH betaine 1. In 27, the nitrogen, rather than the oxygen, occupies an apical position of the trigonal bipyramidal phosphorus violating the commonly assumed preference rules for apicophilicity. It is shown that the previously reported azide derivative 3, obtained from the reaction of 11 with DIAD, undergoes a Curtius-type rearrangement to lead to the fused cyclodiphosphazane [(CH(2)(6-t-Bu-4-Me-C(6)H(2)O)(2))P(OC(O-i-Pr)NN(CO(2)-i-Pr)N)](2) (28); this compound is in equilibrium with its monomeric form in solution at >300 K. Finally, reaction of S(6-t-Bu-4-Me-C(6)H(2)O)(2)P(OPh) (13) with DIAD gave the hexacoordinate compound S[6-t-Bu-4-Me-C(6)H(2)O](2)P(OPh)[N(CO(2)-i-Pr)NC(O-i-Pr)O] (30) with an intramolecular S-->P bond. X-ray crystallographic evidence for compounds 16, 19, 21, 22, 25, 27, 28, and 30 has been provided.

In‐loop flow [11C]CO2 fixation and radiosynthesis of N,N′‐[11C]dibenzylurea

“…Without this simple addition, the reaction could feasibly be simply occurring in the product vial that receives the reaction mixture, during the time taken to measure product radioactivity and prepare the sample for HPLC analysis. The active Mitsunobu intermediate formed is a Morrison‐Brunn‐Huisgen betaine, which will react with protic substrates: alcohols, amines, and carboxylic acids . Our own non‐radioactive experiments have confirmed that this betaine reacts with water forming the tri‐ n ‐butylphosphine oxide (PBu 3 O) and di‐ tert ‐butyl hydrazodiformate (DBAD‐H 2 ).…”

“…The active Mitsunobu intermediate formed is a Morrison-Brunn-Huisgen betaine, which will react with protic substrates: alcohols, amines, and carboxylic acids. [33][34][35][36][37] Our own non-radioactive experiments have confirmed that this betaine reacts with water forming the tri-n-butylphosphine oxide (PBu 3 O) and di-tert-butyl hydrazodiformate (DBAD-H 2 ). Therefore, in the 11 C-urea synthesis, any remaining unreacted urea-forming betaine will react with the excess water (in the product vial) upon leaving the reaction loop, ensuring that the crude-HPLC is representative of the 11 C-labelled species formed inloop, not in-vial.…”

A Green Approach for Copper-Free Sonogashira Reaction of Aryl Halides with Phenylacetylene in the Presence of Nano-Pd/Phosphorylated Silica (SDPP/Pd0)

“…In the case of aryl Products are known compounds. [14][15][16][17][18][19][20][21][22][23] iodides and activated aryl bromides, the reaction mixture was placed in a 1008C oil bath; and in the case of the less active and deactivated aryl bromides and chlorides, the reaction mixture was placed in a 1208C oil bath. After completion of the reaction, the catalyst was removed by centrifugation and the remaining mixture was extracted with ethyl acetate (3 Â 10 mL) and water several times and dried over anhydrous Na 2 SO 4 .…”

“…In all the above-performed reactions, the amount of palladium supported on SDPP was 0.001 g (0.5 mol-%). When the catalyst amount increased from 0.001 to 0.002 and 0.003 g, the reaction time decreased from 3 to 2 and 1 h, respectively (Table 1, entries 16,17). The effect of CuI on the reaction was also investigated.…”

Tetrazine Assists Reduction of Water by Phosphines: Application in the Mitsunobu Reaction

“…The Mitsunobu DEAD phosphine betaine (Scheme 4) was never characterized by X-ray diffraction but af ew examples of its protonated form are known. [21] In contrast to the above,a fter addition of 1equiv of Et 2 O·HBF 4 to an acetonitrile solution of a1 :1 mixture of PEt 3 and compound 5, no color change was observed (Scheme 7). Proton NMR spectroscopy shows unchanged signals of 3,6-diphenyltetrazine and formationo fE t 3 PH + ,w hose acidic proton appearsa sad oublet at d = 5.8 ppm with al arge J H,P = 480 Hz; the 31 PNMR spectrum shows ap eak at d = 22.3 ppm, in agreement with the literature value.…”