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

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.

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

References and Notes

For asymmetric intermolecular alkylation via memory of chirality, see:

1a Kawabata T. Yahiro K. Fuji K. J. Am. Chem. Soc.  1991,  113:  9694 

1b Kawabata T. Wirth T. Yahiro K. Suzuki H. Fuji K. J. Am. Chem. Soc.  1994,  116:  10809 

1c Kawabata T. Suzuki H. Nagae Y. Fuji K. Angew. Chem. Int. Ed.  2000,  39:  2155 

For asymmetric intramolecular alkylation via memory of chirality, see:

2a Kawabata T. Kawakami S. Majumdar S. J. Am. Chem. Soc.  2003,  125:  13012 

2b Kawabata T. Matsuda S. Kawakami S. Monguchi D. Moriyama K.
J. Am. Chem. Soc.  2006,  128:  15394 

2c Kawabata T. Moriyama K. Kawakami S. Tsubaki K. J. Am. Chem. Soc.  2008,  130:  4153 

3 For asymmetric intramolecular conjugate addition via memory of chirality, see: Kawabata T. Majuumdar S. Tsubaki K. Monguchi D. Org. Biomol. Chem.  2005,  3:  1609 

4 For Dieckmann condensation via memory of chirality, see: Watanabe T. Kawabata T. Heterocycles  2008,  76:  1593 

For recent reviews on asymmetric synthesis via memory of chirality see:

5a Kawabata T. Fuji K. Top. Stereochem.  2003,  53:  175 

5b Zhao H. Hsu D. Carlier PR. Synthesis  2005,  1 

5c Kawabata T. Asymmetric Synthesis and Application of α-Amino Acids   ACS Symposium Series 1009:  American Chemical Society; Washington DC: 2009.  p.31-56  

6 Basel Y. Hassner A. J. Org. Chem.  2000,  65:  6368 

7 Brunner M. Saarenketo P. Straub T. Rissanen K. Koskinen AMP. Eur. J. Org. Chem.  2004,  3879 

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 S_Ei 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.

10a Mermerian AH. Fu GC. J. Am. Chem. Soc.  2003,  125:  4050 

10b Shaw SA. Aleman P. Vedejs E. J. Am. Chem. Soc.  2003,  125:  13368 

10c Shaw SA. Aleman P. Christy J. Kampf JW. Va P. Vedejs E. J. Am. Chem. Soc.  2006,  128:  925 

11a Takayama E. Nanbara S. Nakai T. Chem. Lett.  2006,  35:  478 

11b Takayama E. Kimura H. Angew. Chem. Int. Ed.  2007,  46:  8869 

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.