Chiral spiro-β-lactams from 6-diazopenicillanates

• Published in: Tetrahedron Vol. 68; no. 19; pp. 3729 - 3737
• Main Authors: Santos, Bruna S., Nunes, Sandra C.C., Pais, Alberto A.C.C., Pinho e Melo, Teresa M.V.D.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 13.05.2012; Elsevier
• Subjects: 1,3-Dipolar cycloaddition; 6-Diazopenicillanates; Acrylonitriles; Alkynes; Chemistry; Chemistry, Organic; Cycloaddition; Denitrogenation; Derivatives; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Ketones; Mathematical analysis; Organic chemistry; Physical Sciences; Preparations and properties; Ring contraction; Science & Technology; Spiro-1-pyrazoline-β-lactams; Spiro-2-pyrazoline-β-lactams; Spiro-3H-pyrazole-β-lactams; Spirocyclopropyl-β-lactams; Tetrahedrons; 1,3-Dipolar cycloaddition; 6-Diazopenicillanates; Spiro-3H-pyrazole-β-lactams; Spiro-1-pyrazoline-β-lactams; Ring contraction; Spirocyclopropyl-β-lactams; Spiro-2-pyrazoline-β-lactams; Spiro-3H-pyrazole-beta-lactams; ASYMMETRIC-SYNTHESIS; ENANTIOSELECTIVE SYNTHESIS; STEREOCHEMISTRY; DIAZO-COMPOUNDS; Spiro-2-pyrazoline-beta-lactams; THERMAL-DECOMPOSITION; CYCLOADDITION; Spirocyclopropyl-beta-lactams; DENITROGENATION; STEREOSELECTIVE-SYNTHESIS; INHIBITORS; Spiro-1-pyrazoline-beta-lactams; ALKYLIDENECYCLOPROPANE; Acrylic acid ester; Acrylonitrile; Acetylenic compound; Nitrogen heterocycle; Lactam; Microwave; Chiral compound; Selectivity; Stereoselectivity; Imide; Pyrazole derivatives; Dipolarophile; Chemical synthesis; Denitrogenation; Sulfur nitrogen heterocycle; Maleimide derivative; β-Lactams; Theoretical study; Steric hindrance; Spiran; Electronic structure; Diazo compound; But-3-en-2-one; Alkyne
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2012.03.022

Chiral spiro-β-lactam derivatives have been prepared via stereoselective 1,3-dipolar cycloaddition of 6-diazopenicillanates. Using dipolarophiles such as acrylonitrile, acrylates or methyl vinyl ketone spiro-2-pyrazoline-β-lactams were obtained, whereas the cycloaddition with N-substituted-maleimides afforded spiro-1-pyrazoline-β-lactams. 6-Diazopenicillanates also reacted with electron-deficient alkynes to give the corresponding spiro-3H-pyrazole-β-lactam as single product. The observed stereoselectivity can be explained considering that the major product results from the addition to the less sterically hindered α-side of the β-lactam. Microwave-induced denitrogenation of spiro-1-pyrazoline-β-lactams allowed the stereoselective synthesis of novel spirocyclopropyl-β-lactams. The rationalization of the observed selectivity was supported by electronic structure calculations. [Display omitted]