Phosgenation Reactions - Phosgenations - page 446

Ph 3 P

+

BSMN 3

BSM N PPh 3 BSM N O

THF
25°C
2 h

1735 86 %

1736

81 %
1737

CO 2

ether, 25°C, 5 min

Ph 3 P=O
benzene
reflux
1 h

BSM

N N

BSM

76 %
1738

BSM = bis(trimethylsilyl)methyl

Bis(trimethylsilyl)methyl isocyanate 1737: Carbon dioxide was bubbled into a solu-
tion of 1736 (6.00 g, 13.77 mmol) in diethyl ether (25 mL) at 25 C for 5 min. The
Ph 3 PO produced was filtered off, and the solvent was removed from the filtrate.
Fractional distillation of the oily residue (63-65 C, 20 Torr) gave 2.25 g (81%) of
1737.
N,N 0 -Bis[ bis(trimethylsilyl)methyl]carbodiimide 1738: Iminophosphorane 1736
(0.85 g, 1.95 mmol) and isocyanate 1737 (0.39 g, 1.94 mmol) were reacted in re-
fluxing benzene (25 mL) for 1 h. The solvent was then removed in vacuo, and the
crude reaction mixture was treated with n-pentane (50 mL). After filtration of the
Ph 3 PO produced and evaporation of the solvent, flash chromatography of the resi-
due (SiO 2 ; n-pentane/Et 2 O, 14:1) gave 0.53 g (76%) of carbodiimide 1738 as an oil.
By aza-Wittig reactions of iminophosphoranes with isocyanates, carbodiimide-
mediated syntheses of pyrrole and indole derivatives [1270], pentasubstituted
pyridines [1271], pyrimidine derivatives [1272-1274], bis(b-ferrocenylvinyl)carbo-
diimide [1274], amino-tetrazolyl-deoxythymidines [1275], the marine alkaloid leu-
cettamine B [1276], and aza-analogues of aplysinopsins [1277] have also been ac-
complished.

Mitsunobu reagent (diethyl azodicarboxylate/triphenylphosphine)
Alkyl- and aryl carbodiimides can be prepared under mild conditions from thiour-
eas with diethyl azodicarboxylate/triphenylphosphine (Mitsunobu reagent), typi-
cally in yields of around 80%; the by-products are triphenylphosphine sulfide and
diethyl hydrazodicarboxylate [1278]. The active intermediate in this system is the
betaine 1739, which is formed from diethyl azodicarboxylate (DEAD) and triphe-
nylphosphine. Driven by its charge distribution and its chalcogenophilicity, 1739
reacts with the thiourea 1740 to form the P,S bond in 1741. This energy-rich
molecule stabilizes by decomposition into three molecules, namely the two by-
products, triphenylphosphine sulfide and diethyl hydrazodicarboxylate, and the
desired carbodiimide 1699. Diphenylcarbodiimide 1699 (R R 0 ¼ ¼ Ph) was pre-

pared from N,N 0 -diphenylthiourea 1740 (R R 0 ¼ ¼ Ph) with DEAD and triphenyl-

phosphine in 65% yield [1278].