Synthesis of fluorinated chirons: Stereoselective oxirane formation by reaction of diazomethane on 1-fluoro-3-arylsulfinyl-2-propanone and ring opening by selected nucleophiles

Stereoselective Nucleophilic Fluoromethylation of Aryl Ketones: Dynamic Kinetic Resolution of Chiral α‐Fluoro Carbanions

“…75:25; Scheme ) 7a. In 1995, the same group reported a stereoselective oxirane formation from chiral 1‐fluoro‐3‐arylsulfinyl‐2‐propanone with diazomethane, and monofluoromethyl tertiary alcohols were obtained after the ring‐opening reaction (Scheme ) 7b. In this case, although the first step gave the oxiranes in good d.r.…”

Epihalohydrins in Organic Synthesis

“…Thus, they have examined the synthesis of (2 S , R S )-oxirane 424 from ( R )-1-fluoro-3-[(4-methylphenyl)sulfinyl]-2-propanone ( 423 ), prepared through acylation of the lithium derivative of (+)-( R )-methyl-4-methylphenyl sulfoxide with ethyl fluoroacetate. Different reaction conditions have been tested, involving variation of the solvent (Et 2 O, MeOH, benzene) and the reaction temperature (−78 °C, −15 °C, 0 °C, 25 °C), and appropriate selection of the optimal experimental conditions (Scheme ) has led to the preparation of (2 S , R S )-oxirane ( 424 ), which could be isolated in pure form through fractional crystallization or column chromatography in good yield and with high diastereomeric excess (88%). , The reaction mechanism involved was explained by the methylene transfer from diazomethane to the carbonyl group of β-keto-γ-fluorosubstituted sulfoxide ( 423 ), and the high chemo- and diastereoselectivity was considered to be controlled by the unique ability of the sulfinyl group to participate in diazomethane coordination and, simultaneously, in the facial selectivity control of the approaching reagent. , Furthermore, the high diastereoselectivity in favor of (2 S , R S )-oxirane ( 424 ) may also be related to the presence of a strong electron-withdrawing group such as fluorine in the α-position to the carbonyl functionality in the starting sulfoxide 423 , because similar results were obtained when the corresponding bromo and chloro derivatives were used, whereas analogous methyl and hydroxymethyl carbonyl derivatives reacted with very low or no stereoselectivity. , This methodology has been expanded by the same research group to enantiopure oxirane derivatives bearing an additional alkyl group in the α-position with respect to the sulfoxide functionality, leading to the corresponding oxirane derivatives in high chemical yields and in synthetically useful levels of diastereoselectivity (de >70%) …”

“…325 In another example, Bravo and co-workers have studied the enantioselective synthesis of (R)-356 and (S)-2-chloromethyl-2-(sulfinylmethyl)oxiranes (357) via transfer of methylene from diazomethane to the carbonyl group of enantiomerically pure 1chloro-3-p-toluenesulfinylacetone (354) (Scheme 115). 326 To exploit the reactivity of the sulfinyl moiety, the Pummerer rearrangement has been used to remove the sulfinyl group in (R)-2-chloromethyl-2-(sulfinylmethyl)oxirane (356) with the introduction of an oxygen functionality in its place to yield 2formyl-2-(chloromethyl)oxirane (358). The latter compound was further transformed into 2-hydroxymethyl-2-(chloromethyl)oxirane (360) and glycidyl acid (359) by reduction and oxidation, respectively (Scheme 116).…”

“…356,357 The reaction mechanism involved was explained by the methylene transfer from diazomethane to the carbonyl group of β-keto-γ-fluorosubstituted sulfoxide (423), and the high chemo-and diastereoselectivity was considered to be controlled by the unique ability of the sulfinyl group to participate in diazomethane coordination and, simultaneously, in the facial selectivity control of the approaching reagent. 356,357 Furthermore, the high diastereoselectivity in favor of (2S,R S )-oxirane (424) may also be related to the presence of a strong electron-withdrawing group such as fluorine in the α-position to the carbonyl functionality in the starting sulfoxide 423, because similar results were obtained when the corresponding bromo and chloro derivatives were used, whereas analogous methyl and hydroxymethyl carbonyl derivatives reacted with very low or no stereoselectivity. 356,357 This methodology has been expanded by the same research group to enantiopure oxirane derivatives bearing an additional alkyl group in the α-position with respect to the sulfoxide functionality, leading to the corresponding oxirane derivatives in high chemical yields and in synthetically useful levels of diastereoselectivity (de >70%).…”

Asymmetric Synthesis of Fluoroalkyl Amino Compounds via Chiral Sulfoxides

“…The best diastereoselectivity (up to 87/13) was obtained with bulky Grignard reagents, like ww-propyl and wo-butyl derivatives. Methanolysis (55) Several enantiopure compounds having a quaternary monofluoromethyl or Tfmsubstituted carbinolic center C-2, like 2-hydroxy 3-amino acids and 3-deoxy 3-amino glycerols (Scheme 17), were obtained by amine-promoted ring opening of oxiranes (63)(64)(65)(66), prepared by stereocontrolled addition of diazomethane to the corresponding asulfinyl a'-fluoro acetones 67 (d.e. up to 96% when R = H, otherwise d.e.…”