Isocyanide Addition to Acylphosphonates: A Formal Passerini Reaction of Acyl Chlorides

Abstract

Acylphosphonates behave as carbonyl components in Passerini reactions with isocyanides and carboxylic acids. Under saponification, the adducts undergo a phospha-Brook rearrangement to form α-amidophosphates. As acylphosphonates are quantitatively formed from carboxylic derivatives, this new reductive procedure allows acyl chlorides to react as aldehydes in a Passerini-type reaction.

phosphonate - isocyanide - multicomponent reaction - Passerini reaction

References and Notes

For recent reviews, see:

<A NAME="RD05608ST-1A">1a</A> Banfi L. Riva R. Org. React. (N. Y.)  2005,  65:  1 

<A NAME="RD05608ST-1B">1b</A> Zhu J. Eur. J. Org. Chem.  2003,  1133 

<A NAME="RD05608ST-1C">1c</A> Ugi I. Werner B. Dömling A. Molecules  2003,  8:  53 

<A NAME="RD05608ST-1D">1d</A> Hulme C. Gore V. Curr. Med. Chem.  2003,  10:  51 

<A NAME="RD05608ST-1E">1e</A> Bienaymé H. Hulme C. Oddon G. Schmitt P. Chem. Eur. J.  2000,  6:  3321 

<A NAME="RD05608ST-1F">1f</A> Dömling A. Ugi I. Angew. Chem. Int. Ed.  2000,  39:  3168 

<A NAME="RD05608ST-1G">1g</A> Dömling A. Chem. Rev.  2006,  106:  17 

<A NAME="RD05608ST-2">2</A> Nef JU. Justus Liebigs Ann. Chem.  1892,  270:  267 

<A NAME="RD05608ST-3A">3a</A> Ugi I. Fetzer U. Chem. Ber.  1961,  94:  1116 

<A NAME="RD05608ST-3B">3b</A> Westling M. Smith R. Livinghouse T. J. Org. Chem.  1986,  51:  1159 

<A NAME="RD05608ST-3C">3c</A> Lee CH. Westling M. Livinghouse T. Williams AC. J. Am. Chem. Soc.  1992,  114:  4089 

<A NAME="RD05608ST-3D">3d</A> Livinghouse T. Tetrahedron  1999,  55:  9947 

<A NAME="RD05608ST-3E">3e</A> VanWangenen BC. Cardellina JH. Tetrahedron Lett.  1989,  30:  3605 

<A NAME="RD05608ST-3F">3f</A> Adlington RM. Barrett AGM. Tetrahedron  1981,  37:  3935 

<A NAME="RD05608ST-4A">4a</A> Chen JJ. Deshpande SV. Tetrahedron Lett.  2003,  44:  8873 

<A NAME="RD05608ST-4B">4b</A>

See also: ref. 3a and 3f.

<A NAME="RD05608ST-5">5</A> El Kaim L. Pinot-Périgord E. Tetrahedron  1998,  54:  3799 

<A NAME="RD05608ST-6A">6a</A> Oaksmith JM. Peters U. Ganem B. J. Am. Chem. Soc.  2004,  126:  13606 

<A NAME="RD05608ST-6B">6b</A> Richter M. Herrmann C. Augustin M. J. Prakt. Chem.  1980,  322:  434 

<A NAME="RD05608ST-7">7</A> El Kaim L. Gaultier L. Grimaud L. Dos Santos A. Synlett  2005,  2335 

<A NAME="RD05608ST-8A">8a</A> Patel DV. Rielly-Gauvin K. Ryono DE. Free CA. Rogers WL. Smith SA. DeForrest JM. Oehl RS. Petrillo EW. J. Med. Chem.  1995,  38:  4557 

<A NAME="RD05608ST-8B">8b</A> Sun FY. Schmid E. Baumgartner A. Adler T.-D. Mutagenesis  2000,  15:  17 

<A NAME="RD05608ST-8C">8c</A> Chevrier C. Le Nouen D. Defoin A. Tarnus C. Eur. J. Org. Chem.  2006,  2384 

<A NAME="RD05608ST-9">9</A> For a review see: Pudovik AN. Konovalova IV. Synthesis  1979,  81 

<A NAME="RD05608ST-10A">10a</A> Pudovik AN. Konovalova IV. Dedova LV. Zh. Obshch. Khim.  1964,  34:  2902 

<A NAME="RD05608ST-10B">10b</A> Polezhaeva NA. Ovodova OV. Litivinov IA. El’shina EV. Naumov VA. Arbuzov BA. Izv. Akad. Nauk. SSSR, Ser. Khim.  1986,  8:  1860 

<A NAME="RD05608ST-10C">10c</A> Fokin AV. Studnev YN. Rapkin AI. Pasevina KI. Verenikin OV. Kolomiets AF. Izv. Akad. Nauk. SSSR, Ser. Khim.  1981,  7:  1655 

<A NAME="RD05608ST-10D">10d</A> Gallagher MJ. Jenkins ID. J. Chem. Soc. C  1969,  2605 

<A NAME="RD05608ST-11A">11a</A> Hammerschmidt F. Schneyder E. Zbiral E. Chem. Ber.  1980,  113:  3891 

<A NAME="RD05608ST-11B">11b</A> Tromelin A. El Manouni D. Burgada R. Phosphorus Sulfur Relat. Elem.  1986,  27:  301 

<A NAME="RD05608ST-11C">11c</A> Ruel R. Bouvier J.-P. Young RN. J. Org. Chem.  1995,  60:  5209 

<A NAME="RD05608ST-11D">11d</A> Barthel WF. Alexander BH. Giang PA. Hall SA. J. Am. Chem. Soc.  1955,  77:  2424 

<A NAME="RD05608ST-11E">11e</A> Bausch CC. Johnson JS. Adv. Synth. Catal.  2005,  347:  1207 

<A NAME="RD05608ST-12A">12a</A> Pudovik AN. Konovalova IV. J. Gen. Chem. USSR (Engl. Transl.)  1963,  33:  3026 

<A NAME="RD05608ST-12B">12b</A> Fitch SJ. Moedritzer K. J. Am. Chem. Soc.  1962,  84:  1876 

<A NAME="RD05608ST-12C">12c</A> Hammerschmidt F. Zbiral E. Monatsh. Chem.  1980,  111:  1015 

<A NAME="RD05608ST-12D">12d</A> Nguyen LM. Niesor E. Bentzen C. J. Med. Chem.  1987,  30:  1426 

<A NAME="RD05608ST-13A">13a</A> Hall LAR. Stephens CW. Drysdale JJ. J. Am. Chem. Soc.  1957,  79:  1768 

<A NAME="RD05608ST-13B">13b</A> Demir AS. Reis O. Igdir AC. Esiringü I. Eymür S. J. Org. Chem.  2005,  70:  10584 

<A NAME="RD05608ST-13C">13c</A> Demir AS. Reis B. Reis O. Eymür S. Göllü M. Tural S. Saglam G. J. Org. Chem.  2007,  72:  7439 

<A NAME="RD05608ST-13D">13d</A> Demir AS. Reis O. Esiringu I. Reis B. Baris S. Tetrahedron  2007,  63:  160 

<A NAME="RD05608ST-14">14</A> Demir AS. Reis O. Kayalar M. Eymur S. Reis B. Synlett  2006,  3329 

<A NAME="RD05608ST-15">15</A>

General Procedure for the Formation of Phosphonate 5: To acyl chloride 1 (2 mmol) was added neat trialkyl phosphite (1 equiv). The mixture was stirred under argon for 30 min. Toluene (1 M), isocyanide (1 equiv) and carboxylic acid (1 equiv) were then successively added. The mixture was stirred for 24 h under argon at r.t. (for alkyl acyl chlorides) or at 80 °C (for aromatic acyl chlorides). The solvent was then removed under reduced pressure to afford Passerini products after purification by flash column chromatography on silica gel. Data for 5a: mp 72-74 °C; R _f (EtOAc-PE, 50:50): 0.1. ¹H NMR (400 MHz, CDCl₃): δ = 7.26-7.33 (m, 2 H), 7.18-7.24 (m, 3 H), 6.73 (d, J = 8.3 Hz, 1 H), 3.84-3.88 (m, 1 H), 3.88 (d, J _H-P = 10.8 Hz, 3 H), 3.84 (d, J _H-P = 10.6 Hz, 3 H), 2.69-2.80 (m, 1 H), 2.56-2.69 (m, 3 H), 2.18 (s, 3 H), 1.91-1.99 (m, 2 H), 1.68-1.78 (m, 2 H), 1.59-1.66 (m, 1 H), 1.33-1.47 (m, 2 H), 1.17-1.32 (m, 3 H). ¹³C NMR (100.6 MHz, CDCl₃): δ = 169.1 (d, J _C-P = 5.9 Hz), 165.2 (d, J _C-P = 4.4 Hz), 141.4, 129.0, 128.9, 126.5, 83.3 (d, J _C-P = 152.2 Hz), 55.1 (d, J _C-P = 6.6 Hz), 54.5 (d, J _C-P = 7.3 Hz), 49.1, 35.6, 33.2, 33.1, 30.5 (d, J _C-P = 7.3 Hz), 25.9, 25.1, 21.6. IR (thin film): 3328, 3027, 2987, 1749, 1669, 1531, 1259, 1222, 1020 cm^-1. HRMS: m/z calcd for C₂₀H₃₀NO₆P: 411.1811; found: 411.1810.
Typical Procedure for the Conversion of 5a to 6a: To a solution of LiOH (1 mmol) in anhyd THF (0.25 M) was added 5a (1 equiv). The mixture was heated for 2 d at 65 °C under argon. After evaporation of the solvent under reduced pressure, the remaining salts were removed by washing the residue with a 1:1 mixture of CH₂Cl₂ and PE followed by filtration. Evaporation of the solvent gave 6a as a yellow oil in quantitative yield. ¹H NMR (400 MHz, CDCl₃): δ = 7.22-7.30 (m, 2 H), 7.13-7.22 (m, 3 H), 6.46 (d, J = 7.6 Hz, 1 H), 4.70-4.78 (m, 1 H), 3.80 (d, J _H-P = 10.9 Hz, 6 H), 3.75-3.83 (m, 1 H), 2.65-2.76 (m, 2 H), 2.16-2.25 (m, 2 H), 1.83-1.94 (m, 2 H), 1.65-1.76 (m, 2 H), 1.55-1.65 (m, 1 H), 1.27-1.43 (m, 2 H), 1.10-1.27 (m, 3 H). ¹³C NMR (100.6 MHz, CDCl₃): δ = 168.5 (d, J _C-P = 4.4 Hz), 141.1, 128.9, 128.8, 126.5, 78.2 (d, J _C-P = 6.6 Hz), 55.2 (d, J _C-P = 6.6 Hz), 55.1 (d, J _C-P = 6.6 Hz), 48.5, 35.3 (d, J _C-P = 4.4 Hz), 33.4, 33.2, 30.8, 25.8, 25.1. IR (thin film): 3298, 2932, 2856, 1668, 1536, 1452, 1267, 1051 cm^-1. HRMS: m/z calcd for C₁₈H₂₈NO₅P: 369.1705; found: 369.1700.