Diastereoselectivity in the Staudinger reaction of pentafluorosulfanylaldimines and ketimines

Abstract

Summaryβ-Lactams were diastereoselectively formed by the reaction of SF5-containing aldimines, or an SF5-containing ketimine, with benzyloxyketene in a conrotatory ring closure process. Imine formation and cyclization were possible in spite of the acidification of protons on the carbon bound to SF5. The reactions of the aldimines demonstrated very good 1,2-lk diastereoselectivity, however lack of stereochemical control of the C–N ketimine geometry was reflected in the stereochemistry of the product β-lactam. Cyclization of imines with a stereogenic center bearing SF5 was reflected in the 1,2-lk,lk selectivity of the β-lactam.

Pentafluorosulfanyl Chloride

“…The chloropentafluorosulfanyl intermediates were typically 9:1 diastereomeric mixtures (eq 31). 40 High purity of enol ethers proved to be crucial to reach satisfactory yields. α-SF5 Aldehydes were further transformed into α-SF5-substituted aldimines and used in cycloaddition reactions.…”

Preparation and Utility of Organic Pentafluorosulfanyl-Containing Compounds

“…Syntheses and reactions of aldehydes bearing an SF 5 group in the α position have been explored recently, in light of the paucity of information since initial reports of their synthesis and reactions in the 1960s (Scheme ). Aldehydes 207a – g can be formed from acid-catalyzed hydrolysis of adducts 184a – c (24–80% yield), from acetals 185a – c (62–91% yield), or from the α-haloalkyl ether (Scheme ) . Reactions of 207 are representative of organic aldehydes.…”

“…Formation of imines 216e – g from aldehydes 207e – g is easily accomplished by reaction with the desired amine in the presence of MgSO 4 . Conversion of 207e – g to 216e – g using p -anisidine typically occurs in 70–80% conversion overnight with some formation of enamines 217e – g , as indicated by 19 F NMR.…”

Chemistry of α-Oxoesters: A Powerful Tool for the Synthesis of Heterocycles

“…Reaction was conducted by in situ generation of benzyloxyketene using benzyloxyacetyl chloride in the presence of Et 3 N in DCM, followed by addition of a solution of ketimine in DCM and stirring at room temperature for overnight (Scheme 7). 56 Photolysis of cyclohexyl benzoylformate in the presence of various imines was studied by Aoyama et al 57 Reactions were carried out in dry benzene at 80 °C for 3 h, which gave corresponding β-lactams 20 in 27−77% yields. First, hydroxyphenylketene 19 was in situ generated by photolysis of cyclohexyl benzoylformate, and then underwent [2 + 2] cycloaddition reaction with imines to afford β-lactams 20 (Scheme 8).…”

“…Also, β-lactam containing pentafluorosulfanylmethyl substituent 18 was synthesized via Staudinger cycloaddition between ketimine, derived from MgSO 4 -mediated condensation of ethyl pentafluorosulfanylpyruvate with 3 equiv of p -methoxyaniline in DCM, and benzyloxyketene in only 8% yield. Reaction was conducted by in situ generation of benzyloxyketene using benzyloxyacetyl chloride in the presence of Et 3 N in DCM, followed by addition of a solution of ketimine in DCM and stirring at room temperature for overnight (Scheme ) …”