Carbenes, from 1,2,4-oxadiazolines

The 1,3,4-oxadiazole 113 is formed from the azo compound 112 by the action of triphenylphosphine <96SL652>. A general synthesis of 1,3.4-oxadiazolines consists in boiling an acylhydrazone with an acid anhydride (e.g., Scheme 18) <95JHC1647>. 2-Alkoxy-2-amino-l,3,4-oxadiazolines are sources of alkoxy(amino)carbenes the spiro compound 114, for instance, decomposes in boiling benzene to nitrogen, acetone and the carbene 115, which was trapped as the phenyl ether 116 in the presence of phenol <96JA4214>. 

The reaction of ADC compounds with carbenes and their precursors has already been discussed in Section IV,A- In general, the heterocyclic products are not the result of 1,2-addition but of 1,4-addition of the carbene to the —N=N—C=0 system.1 Thus the ADC compound reacts as a 4n unit in a cheletropic reaction leading to the formation of 1,3,4-oxadiazolines. Recent applications include the preparation of spiro-1,3,4-oxadiazolines from cyclic diazoketones and DEAZD as shown in Eq. (14),133 and the synthesis of the acyl derivatives 85 from the pyridinium salts 86.134 The acyl derivatives 85 are readily converted into a-hydroxyketones by a sequence of hydrolysis and reduction reactions. 

In the same vein is the observation that the lifetime of dipropylcarbene (59) in CH2C12 or cyclohexane is 0.3 ns,84 which, after statistical correction is 48 times less than the lifetime ( 21 ns) of Me2C in pentane.22 This reflects promotion by the propyl bystander groups of 59 of the 1,2-H shift to Z- and E-3-heptene.84 (Dipropylcarbene can be photolytically generated from either an oxadiazoline (diazoalkane)84 or diazirine85 precursor, but RIES lowers the efficiency of carbene production in either case.) Recently reported LFP lifetimes for Et2C and MeCEt in cyclohexane or benzene are 0.6-3 ns (cyclohexane) or 1-5 ns (benzene),14 in accord with the lifetimes of S822 and S9.84 The rate constants for carbene disappearance in cyclohexane ( 3 x 108 to 2 x 109 s 1) are presumably limited by 1,2-H shifts.14... 

As part of a mechanistic and synthetic study of nucleophihc carbenes the spirocyclic 4(5/l)-oxazolone 18 has been obtained from benzoyl isocyanate (Scheme 6.1) Thermal extrusion of nitrogen from the 1,3,4-oxadiazoline 14 produced the carbonyl ylide 15 that fragmented via loss of acetone to the aminooxycarbene 16. Spectroscopic data [gas chromatography-mass spectrometry (GC-MS), infrared (IR), proton and C-13 nuclear magnetic resonance ( H and NMR)] of the crude thermolysate was consistent with 18. The formation of 18 was rationalized to result from nucleophihc addition of 16 to benzoyl isocyanate followed by cyclization of the dipolar intermediate 17. Thermolysis of 19 and 21 under similar reaction conditions afforded 20 and 22 respectively, also identified spectroscopically as the major products in the thermolysate. 

At the opposite end of the philicity spectrum, nucleophilic carbenes have proven useful in synthesis. Warkentin" pioneered the thermolysis of oxadiazolines as precursors for (CH30)2C and related dioxacarbenes (Scheme 7.3). Dimethoxycarbene generated from an oxadiazoline undergoes a variety of intermolecular reactions." One example is the ring enlargement of strained cyclic ketones, for example, cyclo-butanone. In this reaction, the nucleophilic carbene initiates the ring expansion by... 

Bis(alkylthio)carbenes (59) generated by thermal decomposition of the corresponding oxadiazolines have been added to phenyl and vinyl isocyanates to form substituted lactams (60) in good yields. The methodology proved to be compatible with many functionalities. Moving from the bis(alkylthio)carbenes to carbenes derived from ephedrine and methylaminoindanol allowed the development of an asymmetric version of this reaction which provides an efficient route to both enantiomers of hydroisatin (61). ... 

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