Formylation reactions are fundamental operations in synthetic chemistry allowing the incorporation into a given structure formyl groups amenable to further derivatization. Conceptually, the introduction of such groups through the reaction between an electrophilic donor and a nucleophilic acceptor (i.e. organometallic reagent) constitutes a reliable technique with widespread applications. In this Highlight, we summarize the effectiveness of the so called Comins-Meyers amide - [2-(N-methyl-N-formylamino]pyridine – in such a chemistry with vistas to the synthesis of natural products and biologically active substrates.
(a) PaceV., HolzerW., OlofssonB. (2014) Increasing the reactivity of amides towards organometallic reagents: An overview. Advanced Synthesis and Catalysis, 356, 3697–3736;(b) Pace V, Holzer W. (2013) Chemoselective activation strategies of amidic carbonyls towards nucleophilic reagents. Australian Journal of Chemistry, 66, 507–510.
2.
OlahG.A., OhannesianL., ArvanaghiM. (1987) Formylating agents. Chemical Reviews, 87, 671–686.
3.
GattermannL., KochJ.A. (1897) Eine synthese aromatischer aldehyde. Berichte der Deutschen Chemischen Gesellschaft, 30, 1622–1624.
4.
RiecheA., GrossH., HöftE. (1960) Über α-Halogenäther, IV. Synthesen aromatischer aldehyde mit dichlormethyl-alkyläthern. Chemische Berichte, 93, 88–94.
5.
DeHaanF.P., DelkerG.L., CoveyW.D., BellomoA.F., BrownJ.A., FerraraD.M., MacArthurC.J. (1984) Electrophilic aromatic substitution. A kinetic study of the formylation of aromatics with 1, 1-dichloromethyl methyl ether in nitromethane. The Journal of Organic Chemistry, 49, 3963–3966.
6.
OlahG.A., KuhnS.J. (1960) Formylation with formyl fluoride: A new aldehyde synthesis and formylation method. Journal of the American Chemical Society, 82, 2380–2382.
7.
OlahG.A., VankarY.D., ArvanaghiM., SommerJ. (1979) Formic anhydride. Angewandte Chemie International Edition in English, 18, 614–614.
8.
HuffmanC.W. (1958) Formylation of amines. The Journal of Organic Chemistry, 23, 727–729.
9.
BöhmeH.W., VieheH.G. (Eds). (1976) Iminium salts in organic chemistry.John Wiley & Sons, New York.
10.
BredereckH., EffenbergerF., HofmannA. (1963) Säureamid-Reaktionen, XXXVI. Thermische zersetzung on trisformaminomethan und bildung on s-triazin. Chemische Berichte, 96, 3260–3264.
11.
(a) OlahG.A., LaaliK., FarooqO. (1985) Aromatic substitution. 52. Superacid-catalyzed carbonylation of aromatics with carbon monoxide. The Journal of Organic Chemistry, 50, 1483–1486;(b) Seyferth D, Hui RC. (1986) A stable 1: 1 lithium acylcyanocuprate. Dependence of the stability of acylcyanocuprates on the nature of the alkyl substituent. Tetrahedron Letters, 27, 1473–1476; (c) Nudelman NS, Vitale AA. (1981) Carbonylation of aryllithium reagents in the presence of alkyl halides: one-pot synthesis of diarylalkyl carbinols and derivatives. The Journal of Organic Chemistry, 46, 4625–4626; (d) Nudelman NS, Outumuro P. (1982) Insertion of carbon monoxide into carbon-lithium bonds. A convenient one-step synthesis of 1, 2-diketone diaryl derivatives. The Journal of Organic Chemistry, 47, 4347–4348; (e) Tsuda T, Miwa M, Saegusa T. (1979) Lithium bis (N, N-diethylcarbamoyl) cuprate. A reagent for direct carbamoylation. The Journal of Organic Chemistry, 44, 3734–3736; (f) Kilbourn MR, Jerabek PA, Welch MJ. (1983) Synthesis of carbon-11 labelled amides via carbonylation of lithium dialkylamides. Journal of the Chemical Society, Chemical Communications, 16, 861–862.
12.
CominsD., MeyersA.I. (1978) A facile and efficient formylation of Grignard reagents. Synthesis, 5, 403–404.
(a) BalasubramaniamS., AidhenI.S. (2008) The growing synthetic utility of the Weinreb amides. Synthesis, 23, 3707–3738;For recent applications of Weinreb amides from our group, see: (b) Pace V, Castoldi L, Holzer W. (2013) Synthesis of alpha, beta-unsaturated-alpha’-haloketones through the chemoselective addition of halomethyllithiums to Weinreb amides. The Journal of Organic Chemistry, 78, 7764–7770; (c) Pace V, Holzer W, Verniest G, Alcántara AR, De Kimpe N. (2013) Chemoselective synthesis of N-substituted α-amino-α’-chloro ketones via chloromethylation of glycine-derived Weinreb amides. Advanced Synthesis and Catalysis, 355, 919–926; (d) Mamuye AD, Castoldi L, Azzena U, Holzer W, Pace V. (2015) Chemoselective efficient synthesis of functionalized β-oxonitriles through cyanomethylation of Weinreb amides. Organic and Biomolecular Chemistry, 13, 1969–1973; For additional examples on the use of organolithium reagents from our group, see: (e) Pace V, Castoldi L, Holzer W. (2014) Chemoselective additions of chloromethyllithium carbenoid to cyclic enones: A direct access to chloromethyl allylic alcohols. Advanced Synthesis and Catalysis.356, 1761–1766; (f) Pace V, Castoldi L, Holzer W. (2013) Addition of lithium carbenoids to isocyanates: a direct access to synthetically useful N-substituted 2-haloacetamides. Chemical Communications, 49, 8383–8385; (g) Pace V, Castoldi L, Mamuye AD, Holzer W. (2014) Homologation of isocyanates with lithium carbenoids: A straightforward access to α-halomethyl- and α,α-dihalomethylamides. Synthesis, 46, 2897–2909; (h) Pace V, Castoldi L, Monticelli S, Safranek S, Roller A, Langer T, Holzer W. (2015) A robust, eco-friendly access to secondary thioamides through the addition of organolithium reagents to isothiocyanates in cyclopentyl methyl ether (CPME). Chemistry – A European Journal, 21, 18966–18970; (i) Pace V, Castoldi L, Mamuye AD, Langer T, Holzer W. (2016) Chemoselective addition of halomethyllithiums to functionalized isatins: A straightforward access to spiro-epoxyoxindoles. Advanced Synthesis and Catalysis, 358, 172–177; (l) Pace V, Pelosi A, Antermite D, Rosati O, Curini M, Holzer W. (2016) Bromomethyllithium-mediated chemoselective homologation of disulfides to dithioacetals. Chemical Communications, 52, 2639–2642; For reviews on the use of lithium carbenoids in analogous processes, see: (m) Pace V. (2014) Halomethyllithium carbenoids: Versatile reagents for the homologation of electrophilic carbon units. Australian Journal of Chemistry, 67, 311–313. (n) Pace V, Holzer W, De Kimpe N. (2016) Lithium halomethylcarbenoids: Preparation and use in the homologation of carbon electrophiles. Chemical Records, 16, 2061–2076; (n) Pace V, Monticelli S, de la Vega-Hernandez K, Castoldi L. (2016) Isocyanates and isothiocyanates as versatile platforms for accessing (thio)amide-type compounds. Organic and Biomolecular Chemistry, 14, 7848–7854; (o) Pace V, Murgia I, Westermayer S, Langer T, Holzer W. (2016) Highly efficient synthesis of functionalized [small alpha]-oxyketones via Weinreb amides homologation with a-oxygenated organolithiums. Chemical Communications, 52, 7584–7587; (p) Pace V, de la Vega-Hernández K, Urban, E, Langer T. (2016) Chemoselective Schwartz Reagent mediated reduction of isocyanates to formamides. Organic Letters, 8, 2750–2753.
15.
MeyersA.I., CominsD.L. (1978) N-methylamino pyridyl amides (mapa) II. An efficient acylating agent for various nucleophiles and sequential addition to unsymmetrical tert-alcohols. Tetrahedron Letters, 19, 5179–5182.
16.
WieckowskaA., FranssonR., OdellL.R., LarhedM. (2011) Microwave-assisted synthesis of Weinreb and MAP aryl amides via Pd-catalyzed heck aminocarbonylation using Mo (CO) 6 or W (CO) 6. The Journal of Organic Chemistry, 76, 978–981.
17.
MeyersA.I., BabiakK.A., CampbellA.L., CominsD.L., FlemingM.P., HenningR., KaneJ.M. (1983) Total synthesis of (-)-maysine. Journal of the American Chemical Society, 105, 5015–5024.
18.
BhandariM.R., SivappaR., LovelyC.J. (2009) Total synthesis of the putative structure of nagelamide D. Organic Letters, 11, 1535–1538.
19.
KoswattaP.B., SivappaR., DiasH.V., LovelyC.J. (2009) Total synthesis of the Leucetta-derived alkaloid calcaridine A. Synthesis, 17, 2970–2982.
20.
ShutskeG.M., RoehrJ.E. (1997) Synthesis of some piperazinylpyrazolo [3, 4-b] pyridines as selective serotonin re-uptake inhibitors. Journal of Heterocyclic Chemistry, 34, 789–795.
21.
EskildsenJ., ØstergaardN., VedsøP., BegtrupM. (2002) Halogen dance in pyrazole 1-oxides: synthesis of pyrazolo [3, 4-c] quinoline 1-oxides. Tetrahedron, 58, 7635–7644.
