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Synlett 2011(4): 543-546  
DOI: 10.1055/s-0030-1259324
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Asymmetric Carbonyl Migration of α-Amino Acid Derivatives via Memory of Chirality

Fumiteru Teraokaa, Kaoru Fujia, Orhan Ozturkb, Tomoyuki Yoshimurab, Takeo Kawabata*b
a Faculty of Pharmacy, Hiroshima International University, 5-1-1 Hirokoshingai, Kure, Hiroshima 737-0112, Japan
b Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan
Fax: +81(774)383197; e-Mail: kawabata@scl.kyoto-u.ac.jp;
Further Information

Publication History

Received 4 December 2010
Publication Date:
13 January 2011 (online)

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Abstract

N-tert-Butoxycarbonylcarbamates of α-amino acid derivatives underwent asymmetric carbonyl migration by treatment with KHMDS in DMF to give α-amino acid derivatives with an additional ester group at the newly formed tetrasubstituted carbon center in up to 99% ee.

Key words

amino acids - chirality - stereoselectivity - tetrasubstituted carbon - carbonyl migration

    References and Notes

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8

The most stable conformer B was generated by a molecular modeling search (MCMM 50,000 steps) with OPLS 2005 force field and GB/SA solvation model for chloroform using MacroModel (V. 9.0); see Supporting Information.

9

The possibility that the present asymmetric migration proceeds without the intervention of an axially chiral enolate cannot be excluded. Alternative route may involve a concerted SEi process. This route was excluded by the experimental results in the case of asymmetric cyclization shown in Scheme  [5] (refs. 2a and 2c). By analogy, we assume that the present asymmetric carbonyl migration would proceed through an axially chiral enolate intermediate.

12

One-Pot Procedure for 2a (Table 2): A solution of Boc2O (105 mg, 0.48 mmol) in DMF (1.0 mL) was added to a solution of 3 (R = Bn; 120 mg, 0.40 mmol) and DMAP (5.0 mg, 0.04 mmol) in DMF (4.1 mL) at r.t. After being stirred for 30 min, the mixture was cooled to -60 ˚C, KHMDS (0.47 M in THF solution, 1.3 mL, 0.60 mmol) was added dropwise to the mixture. The reaction mixture was stirred at -60 ˚C for 3 h and then poured into sat. aq NH4Cl and extracted with EtOAc. The combined organic layers were washed with sat. aq NaHCO3 and brine, dried over Na2SO4, filtered and evaporated in vacuo. The residue was purified by preparative TLC (SiO2, hexane-EtOAc = 9:1) to give (R)-2a (82 mg, 53%, 98% ee) as a colorless oil.
HPLC conditions: Daicel Chiralpak OJ-H; hexane-i-PrOH, 9:1; flow 0.5 mL/min; t R = 8.4 (R), t R = 9.9 (S); [α]D ²5 +2.6 (c = 2.1, CDCl3). ¹H NMR (600 MHz, CDCl3): δ = 7.33-7.38 (m, 5 H), 7.17-7.24 (m, 5 H), 5.91 (ddt, J = 15.1, 9.6, 5.5 Hz, 1 H), 5.20 (d, J = 15.1 Hz, 1 H), 5.16 (ABq, J AB = 12.3 Hz, Δν = 10.6 Hz, 2 H), 5.08 (d, J = 9.6 Hz, 1 H), 3.22-3.29 (m, 1 H), 3.26 (ABq, J AB = 14.4 Hz, Δν = 18.4 Hz, 2 H), 3.19 (dd, J = 13.1, 5.5 Hz, 1 H), 1.29 (s, 9 H). ¹³C NMR (150 MHz, CDCl3): δ = 170.1, 168.5, 135.9, 135.7, 135.2, 130.3, 128.9, 128.53, 128.49, 127.9, 126.8, 116.1, 82.6, 70.8, 67.1, 45.9, 36.8, 27.7. IR (CDCl3): 1728, 1456, 1369, 1190, 1151 cm-¹. ESI-MS (+): m/z = 418 [M + Na], 340, 278, 204. HRMS: m/z calcd for C24H29NO4Na: 418.1994; found: 418.1953.