Acyl triazolium

Keywords Nucleophilic acylation, triazolium salts, thiazolium salts, benzoin reaction, acyloin reaction, Stetter reaction... 

Ketenes also serve as starting materials to NHC-bound enolate equivalents. Ye reported that enantiomerically enriched dihydropyranones bearing quaternary chiral centers could be generated from aryl-substituted ketenes (Scheme 14.22). Likewise, these substrates underwent diastereoselective protonation, presumably via the intermediacy of acyl triazoliums, to give chiral a-arylesters with good... 

In the context of our work in the area of chiral nucleophilic carbenes and their utility in organic synthesis, we have developed a conceptually distinct approach to catalyzed acylation using a-haloaldehydes as acylation precursors. The use of a chiral triazolium salt in the presence of base allows an enantioselective desymme-trization of meio-hydrobenzoin to proceed in 83% ee and good yield ... 

When 2,2-dichloro-3-phenylpropanal 203 is subjected to standard reaction conditions with chiral triazolium salt 75c, the desired amide is produced in 80% ee and 62% yield Eq. 20. This experiment suggests that the catalyst is involved in an enantioselec-tive protonation event. With this evidence in hand, the proposed mechanism begins with carbene addition to the a-reducible aldehyde followed by formation of activated car-boxylate XLII (Scheme 32). Acyl transfer occurs with HOAt, presumably due to its higher kinetic nucleophilicity under these conditions, thus regenerating the carbene. In turn, intermediate XLin then undergoes nucleophilic attack by the amine and releases the co-catalyst back into the catalytic cycle. 

As shown in previous sections, NHCs promote acyl transfer in transesterification reactions. In a similar manner, O C acyl transfer can be achieved with substrates such as 351 in the presence of 0.9 mol% of triazolium pre-catalyst 353 and KHMDS (Scheme 53). Moderate yields are obtained by varying substitution of the oxazole from R = Me, Ph, t-Bu, and t-Pr [171], Deprotonation of the triazolium salt followed by nucleophilic addition to the carbonate moiety of the oxazole results in enolate intermediate LXXXIII and activated carboxylate LXXXIV. Enolate addition and regeneration of the active catalyst provides quaternary stereocenters 352. 

Die Umwandlung von (2-Oxo-alkyl)-l, 2,4-triazolium-Salzen mit Natriumhydrid in Dimethyl-formamid fiihrt zu 4-Acyl-5-amino-imidazolen. Diese Reaktion verlauft iiber offenkettige N-Cyan-formamidine, was in einem Beispiel durch Isolierung des N-Cyan-formamidins und dessen thermische Cyclisierung zum 4-Acyl-5-amino-imidazol nachgewiesen wurde. Die Ausbeuten liegen im allgemeinen um 30%. In einem Fall wurden 60% Ausbeute erzielt [5-Amino-l-(4-chlor-benzyl)-4-(2,4-dichlor-benzoyl)-imidazol Schmp. 220°]373 ... 

The thiazolium-catalyzed addition of an aldehyde-derived acyl anion with a receptor is a valuable synthetic tool leading to the synthesis of highly funtionalized products. Acyl anion receptors include Michael acceptor (Stetter reaction), aromatic aldehyde (benzoin reaction), ketone, nitroalkene, aziridine, activated imine. Recently, nucleophilic addition of acyl anions to unactivated imines has been explored <07CC852>. Treatment of aryl aldehydes with imines 146 in the presence of triazolium salt 147 (20 mol%) and triethylamine (20 mol%) provides the a-amino ketones 148 in good yields. However, this methodology does not work for 4-pyridylaldehyde and tert-buty laldehyde. 

Reactive betaine intermediates are almost certainly involved in many reactions of imidazoles, e.g. base catalyzed deuterium exchange, acylation at C-2, etc. Begtrup (B-76MI40600, p. 143) has implicated betaines in his studies of the nucleophilic hydroxylation of triazolium salts, and one might expect an extension of these researches into the imidazolium series. 

Triazoles with alkyl, aryl or acyl substituents on N-1 or N-4 can be quaternized. Because of the mesomeric distribution of the positive charge on triazolium compounds, representations such as (63) are convenient but the equivalent formula (64) may be used to denote the site at which quaternization has taken place (the mesomeric nature of (64) must be kept in mind of course). Trialkyloxonium tetrafluoroborates are powerful quaternizing reagents (70JOC2246). 

Acylation of 4-amino-1,2,4-triazole occurs on the 4-NH2 group <63JOC543) the result is not trivial as alternatives such as triazolium salt formation are conceptually possible. 

Sodium hydride in DMF at room temperature induces rearrangement of some l,4-dialkyl-4 T-l,2,4-triazolium salts to 5-aminoimidazoles the reaction can be generalized to permit synthesis of 4-acyl-5-aminoimidazoles from readily accessible starting materials, but yields are only moderate (21-60%) [22]. 

Likewise, the fused-ring triazoline adducts 112, obtained from 1-methyl-1,2,4-triazolium-4-(acyl)imides and propiolic ester, undergo rupture at the N—N or C—N bond to yield triazole or pyrazole compounds (Scheme 37) (76CPB2568). 

It is also possible to acylate A -aminoazolium salts, which was demonstrated for 4-amino-i-triazolium (69JPR897), 3-aminothiazolium (74CPB482), 7V-aminoimidazolium and N-aminobenzimidazoIium salts (74JHC781). 

Syntheses of quaternary l-alkyl-3-perfluoroalkyl-4,5-dimethyl-l,2,4-triazolium iodides have led to the disclosure of a variety of new quaternary salts <04JOC1397>. Arylation of 3-alkylthio-5-aryl-l,2,4-triazoles under basic conditions gave 5-alkylthio-l,3-diaryl-l,2,4-triazoles in moderate yields <04JHC201>. Acyl hydrazides 155 reacted with imidates 156 to yield 1,2,4-triazoles 157 followed by Mitsunobu reactions with amino alcohols 158 to give regioisomeric... 

Triazolium salt 176 was a catalytically competent nucleophilic carbene used in the conversion of a-haloaldehydes into acylating agents <04JA9518>. 

In addition to traditional organocatalysis, ionic liquids as new catalytic systems have been explored. The first examples used nonimmobilised OTBDPS-L-Ser, protonated arginine or lysine in the presence of ionic liquids based on l-alkyl-3-methyl imidazolium ([bmim], [hmim], [omim]) or JV-butyl-N-methyl pyrrolidinium ([bmpy]) ions. The systems, in addition to giving the aldol adducts with high yields and ee, are efficient for catalyst recovery and reuse. Since 2010 new structures containing a primary amino acid coupled with a 1,2,3-triazolium salt, an acyl group or a polystyrene have been developed. The more effective ones for the aldol reaction depicted Scheme 12.3 (13, 14 and 15, respectively) are represented in Figure 12.3. 

N-Heterocyclic carbenes (NHCs) have been well known for their unique reactivity to cleave the acyl C—H bond of aldehydes. In 2012, DiRocco and Rovis reported elegant asymmetric a-acylation reactions of tertiary amines 17 with various aldehydes 16 by employing a combination of an NHC catalyst and photoredox catalyst. Since the Breslow intermediate or NHC itself is sensitive to oxidative conditions, a judicious choice of oxidant and photoredox catalyst is crucial. After careful evaluation of the reaction conditions, Ru(bpy)3Cl2 was proved to be the optimal photoredox catalyst and m-dinitrobenzene (m-DNB) as the co-oxidant under irradiation with blue light. The aminoinda-nol-derived NHC C2 (generated in situ from the corresponding triazolium salt using NaH) exhibited the best asymmetric induction. An array of the desired products 18 was obtained in up to 94% yield and 92% ee (Scheme 2.7). 

In 2008, the Scheldt group reported a direct electrophilic amination via homoenolates catalyzed by N-heterocyclic carbenes using l-acyl-2-aryldiazenes as the electrophilic acceptors, which further increased the versatility of the homoenolate chemistry. It is worthwhile to note that only electron-rich substituents on the aryl component of the diazene could result in product formation (up to 84% yield), while electron-poor aryl substituents gave a lowyield (25%). An example of an asymmetric version of this new ami-nation reaction was achieved with the utilization of the chiral triazolium salt developed in their own group, providing the pyrazolidinone product in good yield (61%) and excellent enantioselectivity (90% ee) (Scheme 7.51). 

Scheldt and co-workers reported a cooperative eatalysis process integrating Ti and triazolium-derived NHCs, providing a facile synthesis of cis cyclopentenes with a broad substrate scope. Using the cooperative system that successfully integrates Lewis acid catalysis and NHC catalysis, previously inaeeessible substituted cyclopentenes were provided directly with excellent levels of enantio- and diastereoselectivity (up to 81% yield, 99% ee). The addition of 2-propanol might facilitate the disassociation of the tertiary alkoxide, and therefore accelerate the acylation step to regenerate the NHC catalyst and Ti(0 Pr)4 (Scheme 7.54). 

In 2013, the Chi group realized an NHC-catalyzed asymmetric p-functional-ization reaction of aldehydes via the transformation of saturated aldehydes to formal Michael acceptors via double oxidation. By using the catalyst derived from the chiral amino indanol triazolium salt in combination with quinone as the oxidant, the p-aryl substituted saturated aldehydes were converted to the o,p-unsaturated acyl azolium intermediates which further reacted with 1,3-dicarbonyl compounds or p-keto esters to generate the corresponding 5-lactones. It was found the use of LiCl and 4 A MS as additives was beneficial to improve the ee s of the products. Notably, the p-alkyl substituted saturated aldehydes were not viable substrates, probably due to the reduced acidity of the p-C—H bonds (Scheme 7.118). 

Later, the group used cyclopropenes 49 as acceptors for the intermolecular Stetter reaction. In the presence of electron-rich triazolium salt H4, a variety of aldehydes and cyclopropenes worked well and afforded the acyl-cyclpropanes 50 in up to 98% yield with up to 96% enantiomeric excess (Scheme 20.24). 

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