Mitsunobu zwitterions

A very mild method for the preparation of isocyanates from primary amines (RNH2) and carbon dioxide (CO2) involves the use of a Mitsunobu zwitterion generated from either diisopropyl azodicarboxylate (DIAD) or di-tert-butyl azodicarboxylate and triphenylphosphine or tri-n.-butylphosphine. 

Carbon dioxide and dialkyl azodicarboxylate (Mitsunobu zwitterions) as phosgene substitutes... 

Primary alkylamines give high yields of isocyanates when reacted with carbon dioxide (CO2) and the Mitsunobu zwitterions generated from dialkyl azodicarboxylates and BU3P or PhsP at —78 °C [196, 272]. The aliphatic isocyanates prepared in this way are listed in Table 4.18. 

Intermolecular and intramolecular nucleophilic substitution of an alcoholic hydroxy group by the triphenylphosphine/dialkyl azodicarboxylate redox system is widely used in the synthesis and transformation of natural products and is known in organic chemistry as the Mitsunobu reaction.1951 This reaction starts with formation of the zwitterionic phosphonium adduct 19 (Scheme 9) from triphenylphosphine and diethyl (or diisopropyl) azodicarbox-... 

One of the most widely used procedures for dehydrative coupling and cyclization reactions is the Mitsunobu reaction in which the components are treated with triphenylphosphine and diethyl azodicarboxylate (DEAD, EtOaC—N=N—COiEt). The overall equation for reaction of an alcohol 67 with an acid 68 to form the ester 69 is as shown and the active species is the zwitterionic... 

Under Mitsunobu conditions ( anti ) threo-hydroxy carboxylic acids (144) form (Z)- and ( )-alkenes (150) and (151) and cis- and franj-P-lactones (152) and (149) in various ratios, depending on R and (Table 11). The mechanism (Scheme 3) involves a competition between the HGA and CGA intermediates (145) and (146). For R with a high +M effect e.g. Ph, 2-thienyl etc.), the zwitterion (147) also has to be considered. After rotation to (148), intermediate (145) gives rise to the products (151) and (152). Via (146) the lactone (149) is generated. It is obvious from Table 11 that only large R and R groups lead to CGA (144d and 1441), whereas the rest prefer the HGA pathway. ... 

More recently, Wilson et have used ESI-MS to detect transient intermediates in the Wittig, Mitsunobu and Staudinger reactions directly from solution. Ionic intermediates were directly detected while zwitterionic intermediates were indirectly detected following acid quenching. The systems studied were those which had been previously investigated via P NMR. This work demonstrated that the progress of these reactions can be... 

Mitsunobu-like Processes. Triphenylphosphonium 3,3-dime-thyl-l,2,5-thiadiazolidine 1,1-dioxide (1) can be conveniently utilized as a stable source of [PhsP+J in the promotion of Mitsunobu-like processes. By analogy with the betaine generated by reaction of DEAD and triphenylphosphine, protonation of zwitterionic species 1 by an acidic component HX generates ion pair 2 which on subsequent reaction with an alcohol (ROH) affords oxyphosphonium species (3) and 3,3-dimethyl-1,2,5-thiadiazolidine-1,1-dioxide (4). Finally, Sn2 displacement reaction, occurring with Walden inversion of the alcohol stereochemistry, leads to the coupled product R-X and triphenylphosphine oxide (TPPO) (eq 1). 

Another approach toward the synthesis of aryliminophosphoranes (27) involved a Mitsunobu-type reaction between aromatic amines, diethyl azodicarboxylate (DEAD) and triphenylphosphine at ambient temperature. Pentacoordinated intermediate (28) was formed after nucleophilic addition of the conjugated base of the NH-acid on the Huisgen zwitterions (29). Thus fragmentation of the initial adduct (30) under the reaction conditions provided access to iminophosphoranes (27) after removal of the hydrazide (31) (Scheme 6). 

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