Carbenes, 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. 

Although formally the product of 1,4-addition of the carbene to the ADC 4n unit, 1,3,4-oxadiazolines probably arise via initial nucleophilic attack of the diazo compound to give, after loss of N2, a dipolar intermediate. This intermediate azomethine imine can collapse directly to give the oxadiazoline,... 

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... 

The absolute rate constants for oxygen and sulfur transfer to a range of carbenes (dialkyl, cycloalkylidene, alkylchloro, diaryl, arylchloro, arylalkoxy, and dialkoxy), generated by laser flash photolysis of diazirine or oxadiazoline precursors, were determined. No evidence was seen for ylide formation and a concerted mechanism via an ylide-like transition state was proposed. 

Thermolysis of the oxadiazoline (123) gives rise to the corresponding dialkoxy-carbene, which can be trapped by reaction with f-butanol to form orthoesters. The formation of a regioisomeric mixture of esters was explained by fragmentation of the carbene to radicals (124) which recombine at either end of the allyl system. 

Methoxy[(trimethylsilyl)ethoxy]carbene - obtained by thermolysis of the corresponding oxadiazoline 337 - reacts with Cgo in an unprecedented reaction pathway [383,384]. The expected methanofullerene-[2-i-l]-cycloadduct could not be observed. Instead the two dihydrofullerene adducts 338 and 339 were isolated (Scheme 4.69). They are formed by an unusual addition-rearrangement mechanism that includes the migration of the trimethylsilyl group. 

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... 

In recent years there has been a growing interest in the use of carbonyl ylides as 1,3-dipoles for total synthesis.127-130 Their dipolar cycloaddition to alkenic, alkynic and hetero multiple bonded dipolaro-philes has been well documented.6 Methods for the generation of carbonyl ylides include the thermal and photochemical opening of oxiranes,131 the thermal fragmentation of certain heterocyclic structures such as A3-l,3,4-oxadiazolines (141) or l,3-dioxolan-4-ones132-134 (142) and the reaction of carbenes or car-benoids with carbonyl derivatives.133-138 Formation of a carbonyl ylide by attack of a rhodium carbenoid... 

Evidence in support of a stepwise thermal fragmentation of oxadiazolines in benzene at 110 °C has implicated carbonyl ylide intermediates and oxiranes as unstable precursors of the elimination product, ketene acetals, rather than concerted fragmentation to N2, acetone and carbene.26... 

Similar to internal alkenes, carboxidation of the rubber involves intermediate formation of an oxadiazoline cycle (Figure 7.7). Decomposition of the cycle without cleavage of the C=C bond (route 1) is accompanied by the formation of a ketone and does not lead to change in the molecular weight. Decomposition with cleavage (route 2) leads to fragmentation of the macromolecule with the formation of two smaller fragments a linear aldehyde R2-CH2-CHO and a carbene R -CH2-CH , which further isomerizes into the terminal alkene Rj-CH=CH2. 

Transient carbene (9) is expected to be a reaction intermediate in the transformation of butadiyne-linked triazene (8) to alkyne-linked bis-2//-indazolcs (10).18 Experimental data and DFT calculations support carbene (9) as an intermediate in this stepwise, non-synchronous coarctate reaction. Methoxy(methylthio)carbene (12) has been observed by UV photoelectron spectroscopy after gas-phase decomposition of oxadiazoline (11).19 The oxadiazoline (13) allows the generation of the acetoxy(methoxy)carbene (14) 20 -pjjg reaC jvj y 0f (he latter with isocyanates has been explored. Such reactions generally yield methyl (acetylamino)oxoacetates (15). DFT calculations permitted interpretation of the experimental data. 

Thermolysis of 2-acetoxy-2-methoxy-5,5-dimethyl-A3-l,3,4-oxadiazoline affords acetoxy(methoxy) carbene.60 The thermal rearrangement of acetoxy(methoxy) car-bene to methyl pyruvate was studied by DFT at the B3PW91/6-31G(d,p) level. The conformation of the carbene was considered, as were competing fragmentations to radical pairs. The authors concluded that the reaction is a concerted 1,2-migration rather than a fragmentation-recombination process. 

The photolytic pathway for A -l,3,4-oxadiazolines (22) (Scheme 8) begins with C-N cleavage to form diradicals (23), followed by ester elimination and generation of diazoalkanes (24). Further photolysis gives the corresponding carbenes. In a study of (22b) and (22c), flash-photolysis and two-wavelength continuous... 

Unusual sources for nitrogen-substituted carbenes are 1,3,4-oxadiazolines such as 6. Thermal reaction of 6 with 4-bromo-l-butene furnishes only one diastereomer of spiro-fused /1-lactam cyclopropane 76. However, precursors similar to 6 react less selectively with other olefins. 

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). ... 

Intramolecular addition processes involving latent carbenes have been reported twice. On one hand, the thermolysis of 2,2-dialkoxy-5,5-dimethyl-A -l,3,4-oxadiazolines (38) as latent carbenes formed bicyclic compounds (39) via an efficient and highly stereoselective formal 4- -1-cycloaddition process, carbene (40) being postulated as the key intermediate. On the other hand, the deprotonated carbenic forms of alkyne-tethered imidazolium (41) and 1,2,4-triazolium salts (42) have been found to undergo 6-exo-dig intramolecular addition, leading to zwitterionic intermediates (43) and (44) that rearrange to give 2-substituted imidazole (45) and bicyclic 1,2,4-triazole (46), respectively. ... 

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