Enantioselective [1,2]-Stevens Rearrangement Using Sugar-Derived Alkoxides as Chiral Promoters

Abstract

The first example of enantioselective base-induced [1,2]-Stevens rearrangement was achieved by using the newly developed d-glucose-derived lithium alkoxide as a chiral promoter. This rearrangement provides an α-amino ketone having a pseudoquaternary chiral center in an enantioenriched form.

Key words

asymmetric synthesis - amines - carbohydrates - radical reactions - rearrangements

References and Notes

• 1 Stevens TS. Creighton EM. Gordon AB. MacNicol M. J. Chem. Soc.  1928,  3193 
• For reviews, see:
• 2a Schöllkopf U. Angew. Chem.  1970,  82:  795 
• 2b Markó IE. In Comprehensive Organic Synthesis   Vol. 4:  Trost BM. Fleming I. Pergamon; Oxford: 1991.  p.913-974  
• 2c Vanecko JA. Wan H. West FG. Tetrahedron  2006,  62:  1043 
• For mechanistic studies of [1,2]-Stevens rearrangement, see:
• 3a Millard BJ. Stevens TS. J. Chem. Soc.  1963,  3397 
• 3b Schöllkopf U. Ludwig U. Ostermann G. Patsch M. Tetrahedron Lett.  1969,  10:  3415 
• For theoretical studies of [1,2]-Stevens rearrangement, see:
• 3c Heard GL. Frankcombe KE. Yates BF. Aust. J. Chem.  1993,  46:  1375 
• 3d Heard GL. Yates BF. Aust. J. Chem.  1994,  47:  1685 
• 4a Recently, Somfai and co-workers reported the first example of enantioselective [2,3]-Stevens rearrangement of allylic ammonium ylide using chiral Lewis acid promoter: Blid J. Panknin O. Somfai P. J. Am. Chem. Soc.  2005,  127:  9352 
• 4b

  Also, the concomitantly occurred enantioselective [1,2]-Stevens rearrangement has been reported therein.

• Asymmetric [1,2]-Stevens rearrangement using enantioenriched ammonium ylide has been reported. For the rearrangement with chiral migrating group, see:
• 5a Campbell A. Houston AHJ. Kenyon J. J. Chem. Soc.  1947,  93 
• 5b Brewster JH. Kline MW. J. Am. Chem. Soc.  1952,  74:  5179 
• 5c Joshua H. Gans R. Mislow K. J. Am. Chem. Soc.  1968,  90:  4884 
• 5d Brewster JH. J. Org. Chem.  1969,  354 
• 5e Harada M. Nakai T. Tomooka K. Synlett  2004,  365 
• For the rearrangement with nitrogen chiral center, see:
• 5f Glaeske KW. West FG. Org. Lett.  1999,  1:  31 
• 5g Tayama E. Nanbara S. Nakai T. Chem. Lett.  2006,  35:  478 
• Enantioselective [1,2]-Stevens rearrangement of oxonium ylide generated from a diazo compound using a chiral metal complex has been developed:
• 6a For a representative study using copper(I) complex, see: Nozaki H. Takaya H. Moriuti S. Noyori R. Tetrahedron  1968,  24:  3655 
• For representative studies using dirhodium(II) complex, see:
• 6b Doyle MP. Ene DG. Forbes DC. Tedrow JS. Tetrahedron Lett.  1997,  38:  4367 
• 6c Kitagaki S. Yanamto Y. Tsutsui H. Anada M. Nakajima M. Hashimoto S. Tetrahedron Lett.  2001,  42:  6361 
• 9 For a review of asymmetric synthesis using chiral alkoxide, see: Plaquevent J.-C. Perrard T. Cahard D. Chem. Eur. J.  2002,  8:  3300 
• 10 Alkoxide 3 has been utilized as a chiral ligand for asymmetric Michael reaction. See: Kumamoto T. Aoki S. Nakajima M. Koga K. Tetrahedron: Asymmetry  1994,  5:  1431 
• Alkoxide 4 has been utilized as a chiral promoter for asymmetric hydrocyanation reaction. See:
• 11a Holmes IP. Kagan HB. Tetrahedron Lett.  2000,  41:  7453 
• 11b Holmes IP. Kagan HB. Tetrahedron Lett.  2000,  41:  7457 
• 11c Hatano M. Ikeno T. Miyamoto T. Ishihara K. J. Am. Chem. Soc.  2005,  127:  10776 
• 12 Alkoxide 5 has been utilized as a chiral initiator for asymmetric polymerization. See: Okamoto Y. Matsuda M. Nakano T. Yashima E. J. Polym. Sci., Part A: Polym. Chem.  1994,  32:  309 
• Alkoxide 6 has been utilized as a chiral base for asymmetric elimination and chiral ligand for asymmetric alkynylation. See:
• 13a Soai K. Yokoyama S. Hayasaka T. J. Org. Chem.  1991,  56:  4264 
• 13b Thompson AS. Corley EG. Huntington MF. Grabowski EJJ. Tetrahedron Lett.  1995,  36:  8937 
• 18a Seebach D. Naef R. Helv. Chim. Acta  1981,  64:  2704 
• 18b Beck AK. Seebach D. Chimia  1988,  42:  142 
• 19 Nebel K. Mutter M. Tetrahedron  1988,  44:  4793 
• 20 Absolute stereochemistry of iii was confirmed by the comparison of the specific rotation of its free amine with the reported value. See: Karady S. Amato JS. Weinstock LM. Tetrahedron Lett.  1984,  25:  4337 
• For representative studies on asymmetric synthesis using sugar derivatives as chiral auxiliary, see:
• 21a Kunz H. Mohy J. J. Chem. Soc., Chem. Commun.  1988,  1315 
• 21b Kakinuma K. Li H.-Y. Tetrahedron Lett.  1989,  31:  4157 
• 21c Tomooka K. Nakamura Y. Nakai T. Synlett  1995,  321 
• 21d Kishida M. Eguchi T. Kakinuma K. Tetrahedron Lett.  1996,  37:  2061 
• 21e For a representative study on asymmetric synthesis using sugar derivatives as chiral ligand, see: Riediker M. Duthaler RO. Angew. Chem., Int. Ed. Engl.  1989,  28:  494 
• Synthesis and structural study of alkoxide 8 has been reported. See:
• 22a Piarulli U. Williams DN. Floriani C. Gervasio G. Viterbo D. J. Chem. Soc., Chem. Commun.  1994,  1409 
• 22b Piarulli U. Williams DN. Floriani C. Gervasio G. Viterbo D. J. Chem. Soc., Chem. Commun.  1995,  3329 
• The corresponding alcohols of 10, 11, and 13 have been reported:
• 25a For 10, see: Einhorn C. Luche J. Carbohydr. Res.  1986,  155:  258 
• 25b For 11, see: Luboradzki R. Pakulski Z. Sartowska B. Tetrahedron  2005,  61:  10122 
• 25c For 13, see: Mereyala HB. Kodyry SR. Cheemalapati VN. Tetrahedron: Asymmetry  2006,  17:  259 

7

All the ammonium salts were prepared from the corresponding α-amino ketones and alkyl bromides and purified by recrystallization.

8

Alkoxides were prepared from the corresponding alcohols using n-BuLi (1 equiv) at 0 °C.

14

HPLC analysis was carried out on a Chiralcel OD-H column (0.46 × 25 cm) using hexane-i-PrOH (150:1; 0.5 mL/min) as the mobile phase.

15

A rapid racemization of a similar chiral α-amino ketone under weakly basic conditions had been observed; see ref. 5e.

16

All the compounds were characterized by ¹H and ¹³C NMR analyses. Data for selected products are as follows. 1b: ¹H NMR (300 MHz, CDCl₃): = 8.48 (d, J = 7.5 Hz, 2 H), 7.50-7.70 (m, 8 H), 6.88 (q, J = 7.2 Hz, 1 H), 5.29 (d, J = 12.0 Hz, 1 H), 5.06 (d, J = 12.0 Hz, 1 H), 3.42 (s, 3 H), 3.34 (s, 3 H), 1.79 (d, J = 7.2 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): = 196.8, 135.4, 134.0, 133.6, 131.0, 129.9, 129.5, 129.3, 126.7, 69.4, 66.5, 48.1, 47.0, 14.1. 2b: ¹H NMR (300 MHz, CDCl₃): = 8.46 (d, J = 6.9 Hz, 2 H), 6.90-7.50 (m, 8 H), 3.46 (d, J = 12.3 Hz, 1 H), 2.96 (d, J = 12.3 Hz, 1 H), 2.36 (s, 6 H), 1.18 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 203.1, 137.7, 137.6, 132.5, 130.9, 130.5, 128.3, 128.1, 126.5, 72.2, 41.2, 39.0, 14.5. 14: ¹H NMR (300 MHz, acetone-d ₆): = 5.83 (d, J = 3.6 Hz, 1 H), 4.48 (d, J = 3.6 Hz, 1 H), 4.38 (ddd, J = 6.6, 6.6, 8.4 Hz, 1 H), 4.16 (d, J = 2.7 Hz, 1 H), 4.12 (dd, J = 2.7, 6.6 Hz, 1 H), 4.10 (dd, J = 6.6, 8.1 Hz, 1 H), 3.80 (dd, J = 8.1, 8.4 Hz, 1 H), 2.82 (s, 1 H), 1.90-2.10 (m, 2 H), 1.40-1.60 (m, 10 H), 0.90 (s, 3 H), 0.90 (s, 3 H), 0.88 (s, 3 H), 0.87 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): = 117.2, 112.7, 105.2, 84.6, 82.1, 75.6, 75.0, 71.2, 36.4, 35.6, 34.4, 33.7, 24.8, 23.8, 23.4, 17.4, 17.2.

17

Similar reactions using alkoxides 3-5 afforded racemic 2b in 16-29% yields.

23

Significant countercation-effect for enantioselectivity was observed, i.e., the reaction using the corresponding K or Na alkoxide of 8 afforded only the racemic 2b in moderate yields.

24

The enantioselectivity significantly decreased (18% ee), when one equivalent of 8 was used.

26

Typical Experimental Procedure: To a solution of 1,2-O-cyclohexylidene-5,6-O-(diisopropyl)methylidene-α-d-glucofuranose (14a; 104 mg, 0.29 mmol) in anhyd toluene (2 mL), was added a solution of n-BuLi (0.21 mL of 1.37 M solution in hexane, 0.29 mmol) at 0 °C. After stirring for 30 min at that temperature, benzyldimethyl(α-methylphen-acyl)ammonium bromide (1b; 10.0 mg, 0.029 mmol) was added. Then, the temperature of the resulting solution was allowed to rise to r.t. and the mixture was stirred for 8 h. The reaction was quenched with pH 7 phosphate buffer, and the product was extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO₄, filtered, and the solvent was removed in vacuo. The residue was purified by silica gel chromatography to afford the α-amino ketone (S)-2b (7.0 mg, 91%, 61% ee) and recovered 14a (103 mg, 99%).