Carboxaldehyde derivatives

Ferrocenecarboxaldehyde is a useful starting material for the synthesis of other ferrocene derivatives. It is best prepared by the Vilsmeier formyla-tion reaction using N-methylformanilide in the presence of POCI3 [284, 305, 356, 357]. 

The formyl derivative 7r-CsH4CHOMn(CO)3 has been prepared and it readily oxidizes to the corresponding carboxylic add [358a], viz. 

Several ferrocene derivatives form complexes with other metals, for example, the diketone, pyridoylferrocenylmethyl, chelates with copper(II) [358]. Also an interesting template reaction has been observed [359], viz.. 

Mixed metal complexes such as these and metallocene polymers [360] are of interest in view of the possibility that they may have semi-conductor and related electrical properties in the crystalline state. 

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An alternative route to 5-nitro-2-furancarboxaldehyde requires nitration of 2-furancarboxaldehyde oxime [1121 -47-7] with mixed acid to give the nitrated oxime [555-15-7] and concomitant hydrolysis (22). Furthermore, 2-furan-carboxaldehyde derivatives with the R-substituent in place have been nitrated to the desired product (23). 

A versatile and regioselective synthesis of benzo[b]furans, naphthalenes, indoles and benzothiophenes was achieved by reaction of o-alkynylarene and heteroarene carboxaldehyde derivatives in the presence of iodonium ions. The reaction mechanism was also discussed <06CEJ5790>. 

In a sequence that proceeds by tandem directed ortho metalation steps (Scheme 133) the N,N-diethyl isonicotinamide (447a) has been converted into the chemotherapeutic alkaloid ellipticine (589) (Scheme 182) (80JA1457). Thus, in a rapid, one-pot procedure, metalation of 447a followed by condensation with N-protected indole-3-carboxaldehyde derivatives leads to the intermediates 615 which, upon second metalation and aerial oxidation affords the quinones 616 in modest to good yields. Established steps were used to convert 616, R = CH2OMe into ellipticine (589), concluding a route which complements that based on the oxazolino DMG (Scheme 175). 

When 4-amino-3-carboxaldehyde derivatives of pyridine are employed, 2-amino-l,6-naphthyridines (16) are obtained.6... 

Shinkai and Bruice (21, 22) recently have described the first example of a zinc-ion-catalyzed reduction of aldehyde by NADH and NADH analogs in aqueous solution. They found that 3-hydroxypyridine-4-carboxaldehyde derivatives are reduced by 1,4-dihydropyridines in aqueous methanol (52% by weight) at 30°. Furthermore, this reaction is subject to catalysis by divalent metal ions, including Zn(II), Eq. (9). The following apparent relative order for metal ion effectivenes was observed Ni2+>Co2+>Zn2+>Mn2+>Mg2+>control. 

The same strategy for generating quinodimethane intermediates has been applied to annelation of 2-methylpyrrole-3-carboxaldehyde derivatives (Equation (157)) <92CCI40i>. 

Interestingly, when the same indole-3-carboxaldehyde derivative 65 is subjected to Diels-Alder reactions with Danishefsky s diene (52), either under thermal or hyperbaric activation, it is the aldehyde and not the indole carbon-carbon double bond that serves as the dienophilic component (Scheme 19) [34]. The hetero-Diels-Alder reaction with the carboxaldehyde proceeded at quantitative conversion (82% yield) under thermal conditions (12 equiv Danishefsky s diene, 170°C, 24 h) and provided the cycloadduct 69 in quantitative yield under hyperbaric conditions (12 equiv Danishefsky s diene, 45°C, 96 h, 12 kbar). 

The [Ir(ppy)2bpy] complex photo-catalyses inter- and intramolecular C-H functionalisation reactions of tertiary amines under the visible light irradiation. Oxygen behaves as a chemical switch, triggering different reaction pathways and leading to different products from the same starting material. In anaerobic conditions, the intermolecular addition of iV,iV-dimethyl-anilines to electron-deficient alkenes yields y-amino nitriles. Aerobic conditions, on the other hand, favour a radical addition/ cyclisation reaction, leading to tetrahydroquinoline derivatives. The intramolecular version of the radical addition produces unexpectedly indole-3-carboxaldehyde derivatives. ... 

Heteroaromatic aldehydes are excellent electrophiles in the MBH reaction because of their increased electrophilicity. The heteroatom also facilitates the proton transfers involved in the reaction (Scheme 1.53)/ In the presence of DABCO, pyridine-2-carboxaldehyde derivatives react rapidly with acrylates, methyl vinyl ketone and acrylonitrile to give excellent yields of the MBH adducts 112, which can be further transformed into indolizines 114 by thermal cyclization of their acetate derivatives 113 (Scheme 1.54)/ Notably, a small amount of indolizine 114 was formed along with normal MBH adduct 112 in the reaction of pyridine-2-carboxaldehyde with methyl vinyl ketone. Similarly, substituted 2-chloronicotin aldehydes 115 are reactive and efficient in the MBH reaction of methyl acrylates, acrylonitrile and cyclic enones catalyzed by various tertiary amine catalysts, such as DABCO, DBU, imidazole and 1-methylimidazole, to provide novel MBH adducts 116 and 117 for biological activity screening (Scheme 1.55). ... 

A Knoevenagel condensation followed by intramolecular aldol reaction provides an efficient route to the indolizine core (Scheme 10) (13JOC10395). Pyrrole-2-carboxaldehyde derivatives combined with a number of 1,3-dicarbonyl compounds to provide the indolizines in good yields. 

Various groups were tolerated on the pyrrole-2-carboxaldehyde derivatives (37 other examples, 51-100% yields). 

Starting from 2-hydro yphenylboronic acid and o-bromobenzaldehyde or o-bromonaphthalene carboxaldehyde derivatives as substrates, a number of 6H-benzo[c]chromene-6-ones, 51f-naphtho[l,2-c]chrome-5-ones, and 6H-naphtho[2,l-c]chromene-6-one were synthesized in good yields (Scheme 3.44a). The overall transformation consists of three reactions Suzuki-Miyaura cross-coupling, hemi-acetal formation, and oxidation. By combining 6-diazo-2-cyclohexenone and 2-iodo methylbenzoate as substrates, benzo[c]chromen-6-ones were produced in good yields as well... 

Twenty very uncommon a,co-bis-isothiocyanates have been isolated together from one species of the genus Pseudaxinyssa harvested in Fiji, which also contained three a-isothiocyano-co-carboxaldehyde derivatives. No corresponding isonitrile or N-formylamino analog could be identified and the biosynthesis of these bis-isothiocyanates remains unknown, as well as their function in this particular species of sponge (Karuso and Scheuer, 1987). 

Venkatesham, U., Rao, M.R., and Venkateswarlu, Y. (2000) New 5-alkylpyrrole-2-carboxaldehyde derivatives from the sponge Mycale tenuispiculata. J. Nat. Prod., 63,1318-1320. 

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