3-Pyrroline-1-carbonyl (Pyroc) Group: A Removable Protecting Group for the Kinetic Resolution of Racemic Carboxylic Acids and Alcohols through Catalytic Asymmetric Acylation

Abstract

The O-3-pyrroline-1-carbonyl (O-Pyroc) group and 3-pyrrolinamide are useful removable protecting groups for the kinetic resolution of racemic α-hydroxycarboxylic acids, β-hydroxy­carboxylic acids, 1,2-dicarboxylic acids, and 1,2-diols using the l-histidine-derived bifunctional catalysts. The Pyroc group can be easily introduced from Pyroc chloride. Selective deprotection of the Pyroc group and 3-pyrrolinamide can be carried out via DDQ oxidation followed by hydrolysis using sodium hydroxide, without epimerization.

kinetic resolution - 3-pyrroline-1-carbonyl (Pyroc) - asymmetric acylation - protective and removable - l-histidine framework

References and Notes

For recent reviews, see:

<A NAME="RY00909ST-1A">1a</A> Connon SJ. Lett. Org. Chem.  2006,  3:  333 

<A NAME="RY00909ST-1B">1b</A> Vedejs E. Jure M. Angew. Chem. Int. Ed.  2005,  44:  3974 

<A NAME="RY00909ST-1C">1c</A> Miller SJ. Acc. Chem. Soc.  2004,  37:  601 

<A NAME="RY00909ST-1D">1d</A> Fu GC. Acc. Chem. Res.  2004,  37:  542 

<A NAME="RY00909ST-1E">1e</A> France S. Guerin DJ. Miller SJ. Lectka T. Chem. Rev.  2003,  103:  2985 

<A NAME="RY00909ST-2">2</A> Ishihara K. Kosugi Y. Umemura S. Sakakura A. Org. Lett.  2008,  10:  3191 

For recent reports of asymmetric derivatization of racemic alcohols, see:

<A NAME="RY00909ST-3A">3a</A> Sánchez-Roselló M. Puchlopek ALA. Morgan AJ. Miller SJ. J. Org. Chem.  2008,  73:  1774 

<A NAME="RY00909ST-3B">3b</A> Lewis CA. Chiu A. Kubryk M. Balsells J. Pollard D. Esser CK. Murry J. Reamer RA. Hansen KB. Miller SJ. J. Am. Chem. Soc.  2006,  128:  16454 

<A NAME="RY00909ST-3C">3c</A> Lewis CA. Miller SJ. Angew. Chem. Int. Ed.  2006,  45:  5616 

<A NAME="RY00909ST-3D">3d</A> Zhao Y. Rodrigo J. Hoveyda AH. Snapper ML. Nature (London)  2006,  443:  67 

<A NAME="RY00909ST-3E">3e</A> Birman VB. Li X. Org. Lett.  2006,  8:  1351 

<A NAME="RY00909ST-3F">3f</A> Birman VB. Jiang H. Li X. Guo L. Uffman EW. J. Am. Chem. Soc.  2006,  128:  6536 

<A NAME="RY00909ST-3G">3g</A> Birman VB. Guo L. Org. Lett.  2006,  8:  4859 

<A NAME="RY00909ST-3H">3h</A> Birman VB. Jiang H. Org. Lett.  2005,  7:  3445 

<A NAME="RY00909ST-3I">3i</A> Lewis CA. Sculimbrene BR. Xu Y. Miller SJ. Org. Lett.  2005,  7:  3021 

<A NAME="RY00909ST-3J">3j</A> Sculimbrene BR. Xu Y. Miller SJ. J. Am. Chem. Soc.  2004,  126:  13182 

<A NAME="RY00909ST-3K">3k</A> Birman VB. Uffman EW. Jiang H. Li X. Kilbane CJ. J. Am. Chem. Soc.  2004,  126:  12226 

<A NAME="RY00909ST-3L">3l</A> Fierman MB. O’Leary DJ. Steinmetz WE. Miller SJ. J. Am. Chem. Soc.  2004,  126:  6967 

<A NAME="RY00909ST-3M">3m</A> Griswold KS. Miller SJ. Tetrahedron  2003,  59:  8869 

<A NAME="RY00909ST-3N">3n</A> Sculimbrene BR. Morgan AJ. Miller SJ. Chem. Commun.  2003,  1781 

<A NAME="RY00909ST-3O">3o</A> Kawabata T. Stragies R. Fukaya T. Fuji K. Chirality  2003,  15:  71 

<A NAME="RY00909ST-3P">3p</A> Priem G. Pelotier B. Macdonald SJF. Anson MS. Campbell IB. J. Org. Chem.  2003,  68:  3844 

<A NAME="RY00909ST-3Q">3q</A> Pelotier B. Priem G. Campbell IB. Macdonald SJF. Anson MS. Synlett  2003,  679 

<A NAME="RY00909ST-4">4</A> For kinetic resolution of racemic carboxylic acids, see: Shiina I. Nakata K. Onda Y. Eur. J. Org. Chem.  2008,  5887 

<A NAME="RY00909ST-5A">5a</A> Ishihara K. Kosugi Y. Akakura M. J. Am. Chem. Soc.  2004,  126:  12212 

<A NAME="RY00909ST-5B">5b</A> Ishihara K. Kosugi Y. Akakura M. Tetrahedron  2007,  63:  6191 

<A NAME="RY00909ST-5C">5c</A> For an account article, see: Ishihara K. Sakakura A. Hatano M. Synlett  2007,  686 

<A NAME="RY00909ST-6">6</A>

Reduction with lithium aluminium hydride (4 equiv) gave the corresponding 1,2-diol in high yield without epimeri-zation.^²

Pyroc chloride was prepared as follows: Diallylaminocarbonyl chloride was reacted in the presence of Grubbs’ first-generation catalyst (0.5 mol%) under heating conditions (CH₂Cl₂, reflux, 4 h). After the reaction mixture was concentrated, the residue was purified by column chromatography on SiO₂ to give Pyroc chloride in 95% yield.

<A NAME="RY00909ST-7A">7a</A> Ferguson ML. O’Leary DJ. Grubbs RH. Org. Synth.  2003,  80:  85 

<A NAME="RY00909ST-7B">7b</A> Fu GC. Nguyen ST. Grubbs RH. J. Am. Chem. Soc.  1993,  115:  9856 

<A NAME="RY00909ST-8">8</A> For the synthesis of Pyroc chloride by ring-closing metathesis with the aid of microwave irradiation, see: Vo Thanh G. Loupy A. Tetrahedron Lett.  2003,  44:  9091 

<A NAME="RY00909ST-9">9</A> Kagan HB. Fiaud JC. Top. Stereochem.  1988,  18:  249 

<A NAME="RY00909ST-10A">10a</A> Aggarwal VK. Charmant JPH. Fuentes D. Harvey JN. Hynd G. Ohara D. Picoul W. Robiette R. Smith C. Vasse J.-L. Winn CL. J. Am. Chem. Soc.  2006,  128:  2105 

<A NAME="RY00909ST-10B">10b</A> Ohri RV. Radosevich AT. Hrovat KJ. Musich C. Huang D. Holman TR. Toste FD. Org. Lett.  2005,  7:  2501 

<A NAME="RY00909ST-11">11</A>

Experimental Procedure for the Deprotection of Pyroc Group in 6a
To a solution of 6a (0.1 mmol) in dioxane (1 mL) was added DDQ (0.15 mmol), and the mixture was stirred at 85 ˚C for 2 h. After the reaction mixture was cooled to ambient temperature, dioxane was removed under reduced pressure. The residue was purified by column chromatography on SiO₂ to give 7a in 98% yield.
Compound 7a: ^¹H NMR (400 MHz, CDCl₃): δ = 1.05 (s, 9 H), 1.49 (s, 9 H), 4.02 (dd, J = 2.3, 11.0 Hz, 1 H), 4.21 (dd, J = 4.1, 11.0 Hz, 1 H), 5.22 (dd, J = 2.3, 4.1 Hz, 1 H), 6.26 (dd, J = 1.8, 2.3 Hz, 2 H), 7.29 (dd, J = 1.8, 2.3 Hz, 2 H), 7.30-7.48 (m, 6 H), 7.60-7.74 (m, 4 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 19.2, 26.5, 28.0, 63.3, 76.0, 82.9, 112.6, 120.2, 127.8, 129.9, 132.7, 132.8, 135.4, 135.5, 149.9, 166.2.
To a solution of 7a (0.085 mmol) in THF (0.17 mL) and MeOH (0.17 mL) was added 1.5 M aq NaOH (0.085 mL, 0.13 mmol) at 0 ˚C, and the mixture was stirred at 0 ˚C for 0.5 h. The reaction mixture was quenched with 1 M aq HCl and diluted with EtOAc. The organic layer was separated, washed with brine, dried with Na₂SO₄, and concentrated. The residue was purified by column chromatography on SiO₂ to give 8a in 93% yield.
Compound 8a: ^¹H NMR (400 MHz, CDCl₃): δ = 1.04 (s, 9 H), 1.51 (s, 9 H), 3.88 (dd, J = 2.8, 10.6 Hz, 1 H), 3.99 (dd, J = 2.3, 10.6 Hz, 1 H), 4.10 (dd, J = 2.3, 2.8 Hz, 1 H), 7.31-7.47 (m, 6 H), 7.61-7.74 (m, 4 H).

<A NAME="RY00909ST-12">12</A> Mita T. Sasaki K. Kanai M. Shibasaki M. J. Am. Chem. Soc.  2005,  127:  514