Alpha-fluorovinyl Weinreb amides and alpha-fluoroenones from a common fluorinated building block.
Synthesis and reactivity of N-methoxy-N-methyl-(1,3-benzothiazol-2-ylsulfonyl)fluoroacetamide, a building block for Julia olefination, is reported. This reagent undergoes condensation reactions with aldehydes and cyclic ketones to give alpha-fluorovinyl Weinreb amides. Olefination reactions proceed under mild, DBU-mediated conditions, or in the presence of NaH. DBU-mediated condensations proceed with either E- or Z-selectivity, depending upon reaction conditions, whereas NaH-mediated reactions are > or = 98% Z-stereoselective. Conversion of the Weinreb amide moiety in N-methoxy-N-methyl-(1,3-benzothiazol-2-ylsulfanyl)fluoroacetamide to ketones, followed by oxidation, resulted in another set of olefination reagents, namely (1,3-benzothiazol-2-ylsulfonyl)fluoromethyl phenyl and propyl ketones. In the presence of DBU, these compounds react with aldehydes tested to give alpha-fluoroenones with high Z-selectivity. The use of N-methoxy-N-methyl-(1,3-benzothiazol-2-ylsulfanyl)fluoroacetamide as a common fluorinated intermediate in the synthesis of alpha-fluorovinyl Weinreb amides and alpha-fluoroenones has been demonstrated. Application of the Weinreb amide to alpha-fluoro allyl amine synthesis is also shown.
Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, New York 10031, USA.
Arun K
AK
Ghosh
Shaibal
S
Banerjee
Saikat
S
Sinha
Soon Bang
SB
Kang
Barbara
B
Zajc
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D052160:Benzothiazoles / Q000737:chemistry; D005461:Fluorine / Q000737:chemistry*; D005463:Fluoroacetates / Q000737:chemistry; D007202:Indicators and Reagents / Q000737:chemistry; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction
D000577:Amides; D052160:Benzothiazoles; D005463:Fluoroacetates; D007202:Indicators and Reagents; D007659:Ketones; D005461:Fluorine; C007741:fluoroacetamide; C005465:benzothiazole