Synlett 2003(11): 1755-1756
DOI: 10.1055/s-2003-41439
SPOTLIGHT
© Georg Thieme Verlag Stuttgart · New York

(S)-(-)-1-Amino-2-methoxy-pyrrolidine (SAMP) and (R)-(+)-1-Amino-2-methoxypyrrolidine (RAMP) as Versatile Chiral Auxiliaries

M. Mujahid Alam*
Inorganic Chemistry Division, Indian Institute of Chemical Technology, Hyderabad - 500007. India
Fax: +91(40)27160921; e-Mail: mujahid1206@yahoo.com;

Further Information

Publication History

Publication Date:
22 September 2003 (online)

Biographical Sketches

M. Mujahid Alam was born in Hyderabad. He completed his Bachelor’s degree in 1996 and Master’s degree in chemistry in 1999 from Osmania University, Hyderabad, A. P. India. He then joined the Indian Institute of Chemical Technology (IICT) Hyderabad, as a research assistant. At present he is working under the super­vision of Dr. Adapa Srinivas Rao, on his PhD in the area of organic chemistry, in particular metal catalyzed organic reactions.

(S)-(-)-1-Amino-2-methoxypyrrolidine (SAMP) and (R)-(+)-1-amino-2-methoxypyrrolidine (RAMP) are commercially available chiral auxiliaries and have been successfully applied to asymmetric synthesis, especially bioactive natural product synthesis. [1] (S)-(-)-1-Amino-2-methoxypyrrolidine (SAMP) and (R)-(+)-1-amino-2-methoxypyrrolidine (RAMP ) emerged as chiral auxiliaries for a-alkylation in various application during the total synthesis of various complex organic molecules. The a-alkylation generally proceeds via the a-alkylation of SAMP/RAMP hydrazones followed by 1,2-addition and reductive N-N bond cleavage. [2]

Recently SAMP/RAMP chiral auxiliaries was efficiently used as chiral auxiliaries in various important reactions, which includes the palladium catalyzed allylic substitution, [3] asymmetric synthesis of substituted b-formyl d-lactones and furofuran lactones, [4] diastereo- and enantioselective synthesis of syn-2,3-disubstituted, 1,4-diketones, [5] diastereoselective electrophillic fluorination of enatiopure a-silylketones, [6] recemization free cleavage of ketones SAMP hydrazones, [7] diastereo-and enantioselective synthesis of various 1,2-anti tert-butyl sulfanyl amines, [8] asymmetric synthesis of g-amino nitriles and g-amino ketones [9] etc.

Abstracts

(A) An efficient method has recently been developed for the diastero- and enantioselective Michael addition of metalated lactones-SAMP hydrazones to enolates. The lactone esters (S/R,S)-2 were synthesized in good overall yields (37-61%, two steps, high de, ee) by 1,2-addition of metalated lactone SAMP hydrazones to enolate Michael acceptors 2 and subsequent oxidative cleavage of the product of the hydrazones by ozonolysis. The present method represents a bifunctional building block for further synthetic applications. [10]

(B) Enders et al. [11] reported the short diastereo- and enantioselective synthesis of cis-4,5-disubstituted oxazolidin-2-ones using SAMP chiral auxiliary in a four step reaction sequence - a-alkyl­ation, 1,2-addition with subsequent carbamate protection, cyclization and concluding with cleavage of the auxiliary. The title compounds are obtained in moderate yields and in excellent de and ee. The use of RAMP as auxiliary gave cis-(4R,5S) the enantiomer of SAMP gave cis-(4S,5R).

(C) SAMP/RAMP was used in the first asymmetric synthesis of (S)-and (R)-Stigmolane The stereogenic centre at the C-5 position of the pheromone was generated via SAMP/RAMP hydrazone methodology with high enantiomeric purity. [12]

(D) Very recently the asymmetric synthesis of protected 2-keto-1,3-diols and 1,2,3 triols bearing a quaternary stereogenic center starting from 2,2-dimethyl-1,3-dioxan-5-one was reported. [13] The stereogenic centers are generated by sequential a-alkylation using SAMP/RAMP hydrazone methodology and stereoselective reduction of the ketone generated with l-selectride. The key step in the synthesis was a subsequent third metalation and alkylation of intermediate to install the quaternary stereocentre. The products are obtained in good yields and high de and ee

    References

  • 1a Enders D. Thiebes C. Pure. Appl. Chem.  2001,  73:  573 
  • 1b Enders D. In Asymmetric Synthesis   Morrison J.-D. Academic; New York: 1984.  Vol. 3. p.275 
  • 1c Enders D. Klaff M. In Encyclopedia of Reagents for Organic Synthesis   Paquette LA. Wiley; Chichester: 1995.  Vol. 1. p.178 
  • 1d Enders D. Fey P. Kipphardt H. Synthesis  1987,  173 
  • 2a Enders D. Eichenauer H. Tetrahedron Lett.  1977,  18:  191 
  • 2b Enders D. Reinhold U. Tetrahedron: Asymmetry  1997,  8:  1895 
  • 2c Enders D. Lochtman R. Meiers M. Muller S. Lazny R. Synlett  1998,  1182 
  • 2d Enders D. Thiebes C. Synlett  2000,  1745 
  • 2e Enders D. Kirchhoff JH. Synthesis  2000,  2099 
  • 3 Mino T. Imiya W. Yamashita M. Synlett  1997,  583 
  • 4 Enders D. Vazquez J. Raabe G. Eur. J. Org. Chem.  2000,  893 
  • 5 Enders D. Muller P. Klein D. Synlett  1998,  43 
  • 6 Enders D. Faure S. Potthoff M. Runsink J. Synthesis  2001,  2307 
  • 7 Enders D. Hundertmark T. Lazny R. Synlett  1998,  721 
  • 8 Enders D. Schaadt A. Synlett  2002,  498 
  • 9 Enders D. Janeck CF. Runsink J. Synlett  2000,  641 
  • 10 Enders D. Teschner P. Grobner R. Raabe G. Synthesis  1999,  237 
  • 11 Enders D. Kallfass U. Nolte B. Synlett  2002,  1:  33 
  • 12 Enders D. Ridder A. Synthesis  2000,  1848 
  • 13 Enders D. Nuhring A. Runsink J. Raabe G. Synthesis  2001,  1406 

    References

  • 1a Enders D. Thiebes C. Pure. Appl. Chem.  2001,  73:  573 
  • 1b Enders D. In Asymmetric Synthesis   Morrison J.-D. Academic; New York: 1984.  Vol. 3. p.275 
  • 1c Enders D. Klaff M. In Encyclopedia of Reagents for Organic Synthesis   Paquette LA. Wiley; Chichester: 1995.  Vol. 1. p.178 
  • 1d Enders D. Fey P. Kipphardt H. Synthesis  1987,  173 
  • 2a Enders D. Eichenauer H. Tetrahedron Lett.  1977,  18:  191 
  • 2b Enders D. Reinhold U. Tetrahedron: Asymmetry  1997,  8:  1895 
  • 2c Enders D. Lochtman R. Meiers M. Muller S. Lazny R. Synlett  1998,  1182 
  • 2d Enders D. Thiebes C. Synlett  2000,  1745 
  • 2e Enders D. Kirchhoff JH. Synthesis  2000,  2099 
  • 3 Mino T. Imiya W. Yamashita M. Synlett  1997,  583 
  • 4 Enders D. Vazquez J. Raabe G. Eur. J. Org. Chem.  2000,  893 
  • 5 Enders D. Muller P. Klein D. Synlett  1998,  43 
  • 6 Enders D. Faure S. Potthoff M. Runsink J. Synthesis  2001,  2307 
  • 7 Enders D. Hundertmark T. Lazny R. Synlett  1998,  721 
  • 8 Enders D. Schaadt A. Synlett  2002,  498 
  • 9 Enders D. Janeck CF. Runsink J. Synlett  2000,  641 
  • 10 Enders D. Teschner P. Grobner R. Raabe G. Synthesis  1999,  237 
  • 11 Enders D. Kallfass U. Nolte B. Synlett  2002,  1:  33 
  • 12 Enders D. Ridder A. Synthesis  2000,  1848 
  • 13 Enders D. Nuhring A. Runsink J. Raabe G. Synthesis  2001,  1406