Vilsmeyer formylation

Indolizine is much more basic than indole (p Ta = 3.9 vs. —3.5), and the stability of the cation makes it less reactive and resistant to acid-catalyzed polymerization. Protonation occurs at C-3, although 3-methylindolizine protonates also at C-l. Introduction of methyl groups raises the basicity of indolizines. Electrophilic substitutions such as acylation, Vilsmeyer formylation, and diazo-coupling all take place at C-3. Nitration of 2-methylindolizine under mild conditions results in substitution at C-3, but under strongly acidic conditions it takes place at C-l, presumably via attack on the indolizinium cation. However, the nitration of indolizines often can provoke oxidation processes. 

Ferrocene reacts with acetyl chloride and aluminum chloride to afford the acylated product (287) (Scheme 84). The Friedel-Crafts acylation of (284) is about 3.3 x 10 times faster than that of benzene. Use of these conditions it is difficult to avoid the formation of a disubstituted product unless only a stoichiometric amount of AlCft is used. Thus, while the acyl substituent present in (287) is somewhat deactivating, the relative rate of acylation of (287) is still rapid (1.9 x 10 faster than benzene). Formation of the diacylated product may be avoided by use of acetic anhydride and BF3-Et20. Electrophilic substitution of (284) under Vilsmeyer formylation, Maimich aminomethylation, or acetoxymercuration conditions gives (288), (289), and (290/291), respectively, in good yields. Racemic amine (289) (also available in two steps from (287)) is readily resolved, providing the classic entry to enantiomerically pure ferrocene derivatives that possess central chirality and/or planar chirality. Friedel Crafts alkylation of (284) proceeds with the formation of a mixture of mono- and polyalkyl-substituted ferrocenes. The reaction of (284) with other... 

Sternberg et showed that the vinylogous Vilsmeyer formylation of 5,10-diphenylporphyrin 81 gives 82 which, followed by cychzation, resulted in the formation of both the fused-ring system 83 and an oxidized form 84 of the expected primary cychzation product, (Scheme 23). 

Podlech et al. recently reported on a total synthesis of alternariol (732) with a palladium-catalyzed Suzuki-tyipe coupling as the key reaction 495). The synthesis began by preparing the orcinol-derived boronic acid 748 by methylation and subsequent bromination with iV-bromosuccinimide (NBS) of orcinol 746 362), and treatment of 747 with butyUithium, followed by forming the boronic acid with tri/so-propyl borate (496) (Scheme 11.2). The brominated Suzukt-coupling partner was achieved by a Vilsmeyer formylation of 3,5-dimethoxybromobenzene (749) (497), which was further oxidized under Kraus conditions (242) and esterified to obtain the methyl ester 751. 

Isomer distributions have been determined for several electrophilic substitutions of thiophen, such as bromination by Bra and Br+, chlorination by tin tetrachloride, or iodine-catalysed acetylation by acetic anhydride, trifluoroacetylation, and Vilsmeyer formylation. The a. ratios vary from 100 to over 1000, according to the selectivity of the electrophilic agent. The results obtained, together with other data from the literature, permit a test of the applicability of linear free-energy treatments to electrophilic substitution at the a- and j8-positions of thiophen. Plots of log (Xf and log jSf against p for nine reactions were linear, and from the slopes values of = — 0.79 and 0)3+ = — 0.52 were obtained. Serious deviations were observed for mercuration and protodemercuration, while nitration and protodeboronation were not taken into account, as deviation could be expected for various reasons. The linearity was taken as evidence... 

The Vilsmeyer formylation of 3-phenylthiophen yields a 94 6 mixture of 3-phenylthiophen-2-aldehyde and 3-phenylthiophen-5-aldehyde, whereas Friedel-Crafts acetylation with SnCl as catalyst is less selective and yields a 7 3 mixture of 2-acetyl-3-phenyl- and 5-acetyl-3-phenyl-thiophen. ... 

Darzens reported that compounds of type 4 can be dehydrogenated to l-methyl-3-n hthoic acid 22 with the use of sulfur or selenium at elevated temperature. Subsequent decarboxylation using lime yielded 1-methylnaphthalen 23. This sequence of reaction can be carried out in one pot. Through a series of reactions the methyl naphthoic acid 22 can be converted to 4-methyl-2-naphthol 24, and further, with the aid of Vilsmeyer formylation to alkyl naphthofuran 25. ... 

Vilsmeyer-Haack formylation of 7-hydroxy-2,3,6,7-tetrahydro-l//,5//-pyrido[3,2,l-y]quinazoline-l,3-dione with POCI3/DMF gave 7-chloro-6-formyl-2,3-dihydro-l//,5// derivative. Boiling a toluene solution of the aforementioned 7-hydroxy derivative in the presence of pTSA yielded dehydrated 2,3-dihydro derivative (01MI28). 

Under the conditions of the Vilsmeyer reaction, 2,3,4-triphenyl-cyclopentadiene triphenylarsorane (8) was converted to its formylated product (23) (65). 

The formylating agent, also known as the Vilsmeyer-Haack Reagent, is formed in situ from DMF and phosphorus oxychlorid ... 

Vilsmeyer-Haack formylation of the tricyclic compounds of types 205 and 333 with dimethylformamide-phosphoryl chloride reagent gave the formylated products 390 (For the structures of 390... 

As briefly mentioned in Section III. A, 2,4,4,6-tetraphenyl-4//-pyran (8a) was chlorinated, brominated, and even nitrated under mild conditions in positions 3 and 5 to appropriate derivatives 12a (X = Y = Cl, Br, N02) (92CCC546). Vilsmeyer-Haack formylations of 6a (89AP617) and 8a... 

The transformations are acid-catalyzed. It is suggested66 that the previously64 prepared compounds 83 (R1 = H, Me, Ph R2 = R3 = OMe) also exist as dimers. Variously substituted 2-benzazepines, which are the subject of patents,68-68 were prepared by the Bischler-Napieralski reaction of JV-acylated 3-phenylpropylamines using phosphorus pentoxide66 67 and phosphorus oxychloride-phosphorus pentoxide.68 The cyclization of N-formylated phenylalkylamines (82, Rl = Me R2 = H R3 = R4 = 0— CH2—0) with phosphorus oxychloride, designated as the Vilsmeyer intramolecular reaction,69 gave an 82% yield of 19 (R1 = OH R2 = Me R3 = R4 = R7 = H R6 = R8 = O—CH2—0). 

Complementary approaches to mono protected 1,3-dicarbonyl systems in which either the starting or the introduced carbonyl is protected, have been reported. Thus ketone formylation with Vilsmeyer s reagent followed by treatment with ethylene glycol... 

Advincula et al. decorated conventional dendrimers with conjugated dendrons at the periphery [499]. Formylated terthiophene dendron 5.54, which was prepared by Vilsmeyer-Haack formylation of dendron 5.73a (see below), was linked to the periphery of a 64-amine terminated G4-PAMAM dendrimer by reductive amination. The incorporation of Pd or Au nanoparticles in the dendrimer created new hybrid nanomaterials 5.55 (Scheme 1.67). As a consequence of the dendritic architecture, the emission properties... 

This synthetic strategy, however, leads in general to a mixture of isomers differing in the position of the -alkyl groups in certain thiophene rings. Thus e.g. alkyl-substituted 1,4-diketone 116 is cyclized with L.R. to terthiophene 117. On one hand this is bis-acylated to terthiophene 118 which is further converted into the bis-Mamiich base 120. On the other hand, terthiophene 117 is formylated under Vilsmeyer-Haack conditions to the terthiophene carbaldehyde 119. Both compounds are subjected to a Stetter reaction yielding the bis-1,4-diketone 121 which is cyclized by L.R. to the undecamer 122 [Eq. (50)]. 

Several of these // -disubstituted [ C]formamides have demonstrated utility in C-[ " C]formylations of electron-rich aromatic and heteroaromatic substrates via the Vilsmeyer-Haack reaction °. In the presence of POCI3, Cl2(0)P0P(0)Cl2, (COCl)2 or (CF3S02)20 they can C-formylate benzene and naphthalene derivatives that possess an electron-releasing substituent (0-alkyl, S-alkyl, A -dialkyl) as well as anthracene, pyrrole. 

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