1-Hydroxy-2-methyl-2-propyl Isocyanide (HMPI) as a New Convertible Isocyanide for the Ugi Four-Component-Coupling Reaction

Masato Oikawa; Yutaro Sugamata; Manami Chiba; Koichi Fukushima; Yuichi Ishikawa

doi:10.1055/s-0033-1338967

Synlett, Table of Contents

Synlett 2013; 24(15): 2014-2018
DOI: 10.1055/s-0033-1338967

letter

1-Hydroxy-2-methyl-2-propyl Isocyanide (HMPI) as a New Convertible Isocyanide for the Ugi Four-Component-Coupling Reaction

Masato Oikawa*

Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama 236-0027, Japan Fax: +81(45)7872403 Email: moikawa@yokohama-cu.ac.jp

,

Yutaro Sugamata

Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama 236-0027, Japan Fax: +81(45)7872403 Email: moikawa@yokohama-cu.ac.jp

,

Manami Chiba

Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama 236-0027, Japan Fax: +81(45)7872403 Email: moikawa@yokohama-cu.ac.jp

,

Koichi Fukushima

Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama 236-0027, Japan Fax: +81(45)7872403 Email: moikawa@yokohama-cu.ac.jp

,

Yuichi Ishikawa

Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama 236-0027, Japan Fax: +81(45)7872403 Email: moikawa@yokohama-cu.ac.jp

› Author Affiliations

Abstract

All articles of this category

Abstract

The Ugi reaction is a useful four-component coupling reaction for α-(acylamino)amide. However, selective transformation of the two amides is generally difficult. Here, we report 1-hydroxy-2-methyl-2-propyl isocyanide (HMPI) as a new member of a ‘convertible isocyanide’ class used to solve the problem. HMPI is odorless and shows good reactivity in the Ugi reaction to give N-(1-hydroxy-2-methyl-2-propyl) amides, which are smoothly converted into esters upon Zn(OTf)₂-mediated solvolysis. Overall, structurally diverse α-amino acid esters are readily accessible in two steps by using HMPI.

Key words

amides - chemoselectivity - multicomponent reactions - zinc - esters

Full Text

References

References and Notes

1a Ugi I. Angew. Chem. 1959; 71: 386
1b Ugi I, Steinbruckner C. Angew. Chem. 1960; 72: 267

2a Dömling A, Ugi I. Angew. Chem. Int. Ed. 2000; 39: 3168
2b Dömling A. Chem. Rev. 2005; 106: 17
2c El Kaim L, Grimaud L. Tetrahedron 2009; 65: 2153

3a Sutherlin DP, Stark TM, Hughes R, Armstrong RW. J. Org. Chem. 1996; 61: 8350
3b Obrecht D, Abrecht C, Grieder A, Villalgordo JM. Helv. Chim. Acta 1997; 80: 65
3c Studer A, Jeger P, Wipf P, Curran DP. J. Org. Chem. 1997; 62: 2917

4 van Berkel SS, Bögels BG. M, Wijdeven MA, Westermann B, Rutjes FP. J. T. Eur. J. Org. Chem. 2012; 3543

5a Ikoma M, Oikawa M, Gill MB, Swanson GT, Sakai R, Shimamoto K, Sasaki M. Eur. J. Org. Chem. 2008; 5215
5b Oikawa M, Ikoma M, Sasaki M, Gill MB, Swanson GT, Shimamoto K, Sakai R. Eur. J. Org. Chem. 2009; 5531
5c Oikawa M, Ikoma M, Sasaki M, Gill MB, Swanson GT, Shimamoto K, Sakai R. Bioorg. Med. Chem. 2010; 18: 3795
5d Oikawa, M.; Kasori, Y.; Katayama, L.; Murakami, E.; Oikawa Y.; Ishikawa, Y. manuscript in preparation

6 Flynn DL, Zelle RE, Grieco PA. J. Org. Chem. 1983; 48: 2424
7 Juknaitė L, Sugamata Y, Tokiwa K, Ishikawa Y, Takamizawa S, Eng A, Sakai R, Pickering DS, Frydenvang K, Swanson GT, Kastrup JS, Oikawa M. J. Med. Chem. 2013; 56: 2283

8a Keating TA, Armstrong RW. J. Am. Chem. Soc. 1995; 117: 7842
8b Armstrong RW, Combs AP, Tempest PA, Brown SD, Keating TA. Acc. Chem. Res. 1996; 29: 123
8c Keating TA, Armstrong RW. J. Org. Chem. 1996; 61: 8935
8d Keating TA, Armstrong RW. J. Am. Chem. Soc. 1996; 118: 2574

9 Lindhorst T, Bock H, Ugi I. Tetrahedron 1999; 55: 7411

10a Rikimaru K, Yanagisawa A, Kan T, Fukuyama T. Heterocycles 2007; 73: 403
10b Rikimaru K, Yanagisawa A, Kan T, Fukuyama T. Synlett 2004; 41

11a Gilley CB, Buller MJ, Kobayashi Y. Org. Lett. 2007; 9: 3631
11b Isaacson J, Loo M, Kobayashi Y. Org. Lett. 2008; 10: 1461
11c Isaacson J, Kobayashi Y. Angew. Chem. Int. Ed. 2009; 48: 1845

12 Gilley CB, Kobayashi Y. J. Org. Chem. 2008; 73: 4198

13a Linderman RJ, Binet S, Petrich SR. J. Org. Chem. 1998; 64: 336
13b Zhou H, Zhang W, Yan B. J. Comb. Chem. 2009; 12: 206

14 To avoid isolation of unpleasant-smelling isocyanide, an in situ preparation method has been reported, see: El Kaim L, Grimaud L, Schiltz A. Org. Biomol. Chem. 2009; 7: 3024
15 Kita Y, Nishii Y, Higuchi T, Mashima K. Angew. Chem. Int. Ed. 2012; 51: 5723
16 Barluenga J, de Prado A, Santamaría J, Tomás M. Organometallics 2005; 24: 3614
17 Meyers AI, Collington EW. J. Am. Chem. Soc. 1970; 92: 6676
18 Spectroscopic data for HMPI (1): IR (film): 3399, 2985, 2941, 2135, 1657 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 4.03 (br, 1 H), 3.38 (s, 2 H), 1.29 (s, 6 H); ¹³C NMR (100 MHz, CDCl₃): δ = 152.5, 68.9, 58.9, 25.2 (×2). HRMS (ESI, +): m/z [M + H]⁺ calcd for C₅H₁₀ON: 100.0762; found: 100.0764.
19 To a stirred solution of aldehyde (0.0980 mmol) in methanol (0.5 mL) at r.t., were added amine (0.0650 mmol), carboxylic acid (0.0650 mmol), and HMPI (1, 9.0 mg, 0.091 mmol). After stirring at r.t. for 40 h, the mixture was concentrated under reduced pressure. The residue was dissolved in CHCl₃ (1 mL) and washed successively with sat. aq Na₂CO₃ (1 mL), sat. aq NH₄Cl (1 mL), and brine (1 mL). The organic layer was dried over Na₂SO₄ and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (1 g; hexane–EtOAc) to give the Ugi product X.
20 Nicolaou KC, Boddy CN. C, Li H, Koumbis AE, Hughes R, Natarajan S, Jain NF, Ramanjulu JM, Bräse S, Solomon ME. Chem. Eur. J. 1999; 5: 2602
21 Paulvannan K. Tetrahedron Lett. 1999; 40: 1851
22 Oikawa M, Ikoma M, Sasaki M. Tetrahedron Lett. 2005; 46: 415
23 Takeuchi R, Tanabe K, Tanaka S. J. Org. Chem. 2000; 65: 1558
24 A mixture of diamide X (0.011 mmol), zinc trifluoromethanesulfonate (0.20 mg, 0.00055 mmol), and diethyl carbonate (0.0027 mL, 0.022 mmol) in 1-butanol (0.200 mL) was heated to reflux with stirring for 39 h. The mixture was then concentrated under reduced pressure, dissolved in CHCl₃ (1 mL), and washed with water (1 mL). The aqueous layer was extracted with CHCl₃ (2 × 1 mL) and the combined organic layer was washed with brine (1 mL), dried over Na₂SO₄, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (0.6 g; hexane–EtOAc) to give butyl ester Y.

25a Darwish N, Eggers PK, Da Silva P, Zhang Y, Tong Y, Ye S, Gooding JJ, Paddon-Row MN. Chem. Eur. J. 2012; 18: 283
25b Kirchwehm Y, Damme A, Kupfer T, Braunschweig H, Krueger A. Chem. Commun. 2012; 48: 1502

26a Jiang L, Hartley RC, Chan T.-H. Chem. Commun. 1996; 2193
26b Ando H, Manabe S, Nakahara Y, Ito Y. J. Am. Chem. Soc. 2001; 123: 3848
26c Figlus M, Wellaway N, Cooper AW. J, Sollis SL, Hartley RC. ACS Comb. Sci. 2011; 13: 280