•Reaction of α,β-unsaturated fluoroalkyl ketones and dialkyl phosphites was investigated.•A series of phosphonates and phosphates were separated in moderate to good yields.•The excellent regio-selectivity could be obtained in the presence of DBU or DABCO as organocatalyst.Base-controlled selective reactions of α,β-unsaturated trifluoromethyl ketones with dialkyl phosphites were achieved. In the presence of DABCO, the Pudovik reaction took place readily to give the corresponding α-hydroxy phosphonates in high yields under mild conditions. While using DBU as base, the Phospha-Brook rearrangement of α-hydroxy phosphonates formed in the reaction occurred to afford phosphates as final products.A series of phosphonates and phosphates were synthesized in good yields by the reaction of α,β-unsaturated trifluoromethyl ketones and dialkyl phosphites. Excellent regio-selectivity could be obtained in the presence of DBU or DABCO as organocatalyst.Download high-res image (93KB)Download full-size image

AbstractA mild and efficient transition metal-free intramolecular oxyfluorination of alkenyl oximes is demonstrated. The reaction tolerates a range of substrates to give a series of monofluoromethylated isoxazoline derivatives with good yields. The possible pathways are proposed based on the reaction results and control experiments.

Several perfluoroalkanesulfenyl chlorides were prepared from the corresponding perfluoroalkanesulfenic acids in high yields, and their reactions with thiol, amine, arene and alkene were studied. A series of perfluoroalkyl-containing disulfides, sulfonamides, aryl sulfides and α-chlorosulfides were synthesized under mild conditions.

•A series of 1-sulfonyl-1-trifluoromethyl allenes were prepared for the first time.•Cycloaddition reaction of trifluoromethylated allenes with nitrones was investigated.•Trifluoromethylated isoxazolidines were obtained under mild conditions.A series of 1-sulfonyl-1-trifluoromethyl allenes were prepared for the first time from commercial available 2-bromo-3,3,3-trifluoropropene. Cycloaddition reaction of these trifluoromethylated allenes with nitrones occured readily under mild conditions, giving the corresponding trifluoromethylated isoxazolidines in high yields.Download high-res image (101KB)Download full-size image

•In the addition of polyfluoroalkanesulfenic acids to various carbon–carbon double bonds has been investigated.•Both Markovnikov adduct and anti-Markovnikov adduct could be obtained with different alkenes.•The excellent regioselectivity was obtained.The addition of polyfluoroalkanesulfenic acids, in-situ formed from various imines, to CC double bond was investigated. Both Markovnikov adduct and Michael-type adduct could be obtained with different alkenes. A series of sulfoxides were synthesized with excellent regioselectivities under mild conditions.

•The reductive amination of ketones using 2-chloro-1,1,2,2-tetrafluoroethane-1-sulfinamide as auxiliary was investigated.•The amination products were obtained in good yields with excellent diastereoselectivities.•2-Chloro-1,1,2,2-tetrafluoroethane-1-sulfinamide afforded better diastereoselectivities for aliphatic and (E)-α,β-unsaturated ketones.Using chiral 2-chloro-1,1,2,2-tetrafluoroethane-1-sulfinamide as the auxiliary, an efficient one-pot procedure for the asymmetric reductive amination of ketones was achieved in the presence of sodium borohydride. Both aromatic and aliphatic ketones reacted well to give the corresponding sulfinyl amides in good yields with excellent diastereoselectivities.A highly diastereoselective reductive amination of ketones using 2-chloro-1,1,2,2-tetrafluoroethane-1-sulfinamide as auxiliary was developed. Both aromatic and aliphatic ketones reacted well under the reaction conditions, giving the corresponding amination products in good yields with excellent diastereoselectivities.

•The trifluoromethylation of hydroxyl group in benzyl or allyl alcohols were investigated.•Alkyloxydiphenylphosphine was formed as intermediate in this methodology.•A plausible mechanism was proposed on the basis of experimental results.The transformation of hydroxyl group in benzyl or allyl alcohols to trifluoromethyl was achieved via the reaction of the corresponding alkyloxydiphenylphosphine and CuCF3, generated in situ from methyl fluorosulfonyldifluoroacetate and CuI, under mild conditions. A plausible mechanism was proposed on the basis of experimental results.The transformation of hydroxyl group in benzyl or allyl alcohols to trifluoromethyl could tolerate various functional groups and give the trifluoromethylated products via the corresponding alkyloxydiphenylphosphine under mild conditions.

Copper-catalyzed O-arylation of enolates with diaryliodonium salts as arylating reagents was realized successfully. As important building blocks, β-aryloxy carbonyl compounds were obtained in up to 98% yield under mild conditions, and complete control of O-arylation and Z-stereoselectivity were achieved. The origin of the selectivity was also discussed.

A series of tetrasubstituted fluoroalkene derivatives were synthesized by the reaction of α-fluoro-β-carbonyl benzothiazol-2-yl sulfones with various nucleophiles in good yields with high stereoselectivities. The predominant cis configuration of fluorine and alkynyl groups was observed. A single isomer was obtained when a ketone, acetate or amide was used as the substrate in the presence of a base.

•Efficient organocatalyzed reactions of α,α-difluoro-β-keto esters with acetone were investigated.•α,α-Difluoro-β-keto ester could include various functional groups.•The high diastereoselectivity was obtained.Organocatalyzed reactions of α,α-difluoro-β-keto esters with acetone were demonstrated. In the presence of L-proline, the Aldol reaction occurred under mild conditions to give the corresponding tertiary α,α-difluoroalcohols in good yields with high enantioselectivities. Using pyrrolidine as catalyst, the domino Michael-aldol reaction took place readily to give the corresponding addition products in high yields with excellent diastereoselectivities.Synopsis: In the reactions of α,α-difluoro-β-keto esters with acetone, both aldol reaction and domino Michael-aldol reaction could tolerate a broad range of functional groups and give the corresponding products in high stereoselectivity.

•N-2-Chlorotetrafluoroethanesulfinamide was first used as chiral auxiliary in the propargylation of aldimines.•High diastereoselectivity was achieved under mild conditions.•A series of chiral propargylamines were synthesized.Zinc promoted asymmetric Barbier-type homopropargylation of aldimines is demonstrated. 2-Chlorotetrafluoroethanesulfinamide was used as the chiral auxiliary and the corresponding homopropargylamines were obtained in good yields with up to 98% diastereoselectivity under mild conditions.Zn-promoted propargylation of N-2-(chlorotetrafluoroethanesulfin)imines was achieved with good yields and high diastereoselectivities.

A series of 2-chlorotetrafluoroethanesulfinyl ketimines were prepared from 2-chlorotetrafluoroethanesulfinamide and ketones in high yields, and their Strecker reactions with TMSCN have been investigated. High yields and excellent diastereoselectivities were achieved in the presence of a catalytic amount of CsF under mild conditions. The six-membered chairlike models were proposed to account for the high stereoselective Strecker reaction.

A novel fluorine-insertion organocatalyst, which was designed based on the fluorine–ammonium ion gauche effect, was synthesized and used successfully to catalyze the asymmetric Michael addition of cyclic ketones to nitroolefins. High yields and excellent diastereo- and enantioselectivities were achieved under mild conditions. A possible stereochemical model is also proposed.N-Boc-trans-4-hydroxy-l-proline methyl esterC11H19NO5[α]D20=-65.8 (c 0.5, CHCl3)Source of chirality: the precursorAbsolute configuration: (2S,4R)N-Boc-cis-4-fluoro-l-proline methyl esterC11H18FNO4[α]D20=-59.6 (c 0.7, CHCl3)Source of chirality: the precursor and fluorination of hydroxyAbsolute configuration: (2S,4S)N-Boc-cis-4-Fluoro-l-prolinalC10H16FNO3[α]D20=-80.7 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (2S,4S)(S,S)-2-((Pyrrolidin-1-yl)methyl)-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl esterC14H25FN2O2[α]D20=-50.1 (c 1.1, CHCl3)Source of chirality: the precursorAbsolute configuration: (2S,4S)(S,S)-2-((Pyrrolidin-1-yl)methyl)-4-fluoro-pyrrolidineC19H17FN2[α]D20=13.5 (c 1.0, CHCl3)Source of chirality: the precursorAbsolute configuration: (2S,4S)(S)-2-[(R)-2-Nitro-1-phenylethyl]cyclohexanoneC14H17NO396% ee[α]D20=-29.6 (c 1.0, CHCl3)Source of chirality: enantioselective Michael additionAbsolute configuration: (S,R)(S)-2-[(R)-2-Nitro-1-p-methoxyphenylethyl]cyclohexanoneC15H19NO493% ee[α]D20=-23.5 (c 1.1, CHCl3)Source of chirality: enantioselective Michael additionAbsolute configuration: (S,R)(S)-2-[(R)-2-Nitro-1-p-tert-butylphenylethyl]cyclohexanoneC18H25NO388% ee[α]D20=-15.6 (c 1.0, CHCl3)Source of chirality: enantioselective Michael additionAbsolute configuration: (S,R)(S)-2-[(R)-2-Nitro-1-p-chlorophenylethyl]cyclohexanoneC14H16CINO391% ee[α]D20=-27.0 (c 1.5, CHCl3)Source of chirality: enantioselective Michael additionAbsolute configuration: (S,R)(S)-2-[(R)-2-Nitro-1-p-bromophenylethyl]cyclohexanoneC14H16BrNO398% ee[α]D20=-25.7 (c 1.0, CHCl3)Source of chirality: enantioselective Michael additionAbsolute configuration: (S,R)(S)-2-[(R)-2-Nitro-1-ortho-bromophenylethyl]cyclohexanoneC14H16BrNO396% ee[α]D20=-54.0 (c 1.0, CHCl3)Source of chirality: enantioselective Michael additionAbsolute configuration: (S,R)(S)-2-[(R)-2-Nitro-1-(2,4-dichlorophenyl)-ethyl]cyclohexanoneC14H15Cl2NO399% ee[α]D20=-59.6 (c 0.9, CHCl3)Source of chirality: enantioselective Michael additionAbsolute configuration: (S,R)(S)-2-[(R)-1-(Naphthalene-1-yl)-2-nitroethyl]cyclohexanoneC18H19NO398% ee[α]D20=-84.5 (c 0.5, CHCl3)Source of chirality: enantioselective Michael additionAbsolute configuration: (S,R)(S)-2-[(S)-1-(Furan-2-yl)-2-nitroethyl]cyclohexanoneC12H15NO498% ee[α]D20=-13.2 (c 1.0, CHCl3)Source of chirality: enantioselective Michael additionAbsolute configuration: (S,S)(S)-2-[(S)-2-Nitro-1-cyclohexylethyl]cyclohexanoneC14H23NO384% ee[α]D20=-25.0 (c 0.3, CHCl3)Source of chirality: enantioselective Michael additionAbsolute configuration: (S,S)(R)-Tetrahydro-3-[(R)-2-nitro-1-phenylethyl]pyran-4-oneC13H15NO495% ee[α]D20=-36.2 (c 1.0, CHCl3)Source of chirality: enantioselective Michael additionAbsolute configuration: (R,R)2-Nitro-1-phenylethyl cyclopentanone (syn and anti)C13H15NO32:1 dr (syn/anti), 88% ee (syn), 86% ee (anti)[α]D20=-44.2 (c 1.0, CHCl3).Source of chirality: enantioselective Michael additionAbsolute configuration: (S,R)(S)-2-[(R)-2-Nitro-1-phenylethyl]cycloheptanoneC15H19NO380% ee[α]D20=-14.6 (c 1.0, CHCl3)Source of chirality: enantioselective Michael additionAbsolute configuration: (S,R)(S)-2-[(R)-1-(2,3-Dimethoxyphenyl)-2-nitroethyl]cyclohexanoneC11H13NO349% ee[α]D20=-1.5 (c 0.6, CHCl3)Source of chirality: enantioselective Michael additionAbsolute configuration: (S,R)(E)-(S)-2-((S)-1-Nitro-4-phenylbut-3-en-2-yl)cyclohexanoneC16H19NO399% ee[α]D20=-60.1 (c 1.1, CHCl3)Source of chirality: enantioselective Michael additionAbsolute configuration: (S,S)

The copper-catalyzed highly regioselective reaction of internal alkynes with diaryliodonium salts was achieved for the first time. α-Arylketones were obtained in moderate to good yields from arylpropargylic alcohols or aryl alkyl alkynes under mild conditions. It was found that the two kinds of substrates underwent two different arylation–oxygenation pathways under different reaction conditions based on deuterated experiments, controlling experiments, and spectroscopic analysis of reaction intermediates.

•Efficient metal-mediated Reformatsky reaction of bromodifluoromethyl ketones and aldehydes was investigated.•Water is suitable solvent for this transformation.•The reactions of ketones and aldehydes could tolerate a broad range of functional groups.Water is demonstrated as a suitable solvent for an efficient and environmentally friendly method for the synthesis of α,α-difluorinated β-hydroxy carbonyl compounds through the Reformatsky reaction of bromodifluoromethyl ketones with aldehydes in the presence of Zn/CuCl at room temperature.In the Reformatsky reaction, both of ketones and aldehydes could tolerate a broad range of functional groups in water, which is an environment friendly solvent.

o-Quinodimethane (o-QDM) generated from benzosultine was used to extend the pyrrole system for the preparation of octabromo-tetranaphtho[2,3]porphyrins via oxidative aromatization. The properties of these bromoporphyrins were presented and chemical transformation via Pd-catalyzed Suzuki reaction was also effectively achieved.

Regiospecific and diastereoselective aldol type reaction of chiral N-sulfinyl metalloenamines with α,β-unsaturated trifluoromethyl ketones was reported, which affords the corresponding tertiary trifluoromethyl allylic carbinols in high yields with good diastereoselectivities (dr up to 90:10). The reduction of the condensation product 3a with LiBHEt3 and Catecholborane provides CF3-substituted syn- and anti-1,3-amino alcohols 5a and 5b in high yields with excellent diastereoselectivities (dr > 99:1).Graphical abstractRegiospecific and diastereoselective aldol type reaction of chiral N-sulfinyl metalloenamines with α,β-unsaturated trifluoromethyl ketones was reported, which affords the corresponding tertiary trifluoromethyl allylic carbinols in high yields with good diastereoselectivities (dr up to 90:10).Highlights► Regiospecific and diastereoselective aldol type reaction of chiral N-sulfinyl metalloenamines with α,β-unsaturated trifluoromethyl ketones is described. ► The reaction tolerates a wide range of N-(tert-butanesulfinyl) ketimines and α,β-unsaturated trifluoromethyl ketones. ► The reaction provides a practical method for the asymmetric synthesis of tertiary trifluoromethyl allylic carbinols with good diastereoselectivities.

The aza-Henry reaction of chiral fluoroalkyl α,β-unsaturated N-tert-butanesulfinyl ketoimines and nitromethane was achieved in the presence of 0.2 equivalent of anhydrous potassium carbonate to give the corresponding adducts diastereoselectively in high yields. Transformations which highlighted the synthetic potential of these aza-Henry adducts were also performed.

Efficient synthesis of enantiopure polyfluoroalkanesulfinamides (PFSAs) has been achieved. Their application as novel chiral auxiliaries with an electron-withdrawing and 19F NMR monitorable polyfluoroalkyl group was initially demonstrated in an asymmetric Strecker reaction under mild conditions.

o-Quinodimethane (o-QDM) generated from benzosultine was used to extend the pyrrole system for the preparation of octabromo-tetranaphtho[2,3]porphyrins via oxidative aromatization. The properties of these bromoporphyrins were presented and chemical transformation via Pd-catalyzed Suzuki reaction was also effectively achieved.

The aza-Henry reaction of chiral fluoroalkyl α,β-unsaturated N-tert-butanesulfinyl ketoimines and nitromethane was achieved in the presence of 0.2 equivalent of anhydrous potassium carbonate to give the corresponding adducts diastereoselectively in high yields. Transformations which highlighted the synthetic potential of these aza-Henry adducts were also performed.

A series of tetrasubstituted fluoroalkene derivatives were synthesized by the reaction of α-fluoro-β-carbonyl benzothiazol-2-yl sulfones with various nucleophiles in good yields with high stereoselectivities. The predominant cis configuration of fluorine and alkynyl groups was observed. A single isomer was obtained when a ketone, acetate or amide was used as the substrate in the presence of a base.