Yolanda Arroyo

2‐(p‐Tolylsulfinyl)benzyl Halides as Efficient Precursors of Optically Pure trans‐2,3‐Disubstituted Aziridines

Aziridination of (R)-N-sulfinylaldimines (aryl, heteroaryl and alkenyl derivatives) with 2-(p-tolyl sulfinyl)benzyl iodide in the presence of sodium hexamethyl disilazide takes place with almost complete control of the stereoselectivity (facial and anti/syn) and with very high yields affording optically pure N-sulfinyl trans-2,3-disubstituted aziridines 7. Simultaneous removal of both C- and N-p-tolylsulfinyl groups with tBuLi provides the corresponding trans-NH aziridines 8 without affecting their optical purity. Some experimental results suggest these processes evolve through benzyl halocarbenoids as intermediates, whereas theoretical calculations support the formation of benzyl carbanions. These results have served for revising the mechanistic aspects of the reactions of substituted 2-p-tolylsulfinyl benzylcarbanions with electrophiles.

Chiral monofluorobenzyl carbanions: synthesis of enantiopure β-fluorinated β-phenylethylamines.

The preparation of a stabilized monofluorobenzyl carbanion by means of a remote homochiral sulfinyl group and its completely stereoselective reactions with N-p-tolylsulfinylimines are described. The use of these reactions followed by the simultaneous removal of both chiral auxiliaries with tBuLi, which occurs without epimerization at the benzylic position, provides the quickest entry to enantiomerically pure β-fluorinated β-phenylethylamines.

Stereoselective Control of Planar α-Dimethylsulfonium Benzyl Carbanions. Synthesis of Optically Pure trans-Aziridines

(R)-N-sulfinylimine and (S)-N-sulfinylimine react with the ylide derived from (S)-dimethyl-[2-(p-toluenesulfinyl)phenyl]sulfonium salt, affording trans-2,3-disubstituted aziridines. A complete trans selectivity in low facial diastereoselectivity is observed when the configuration at the sulfur atoms of the reagents is the same. Otherwise, when their configurations are different, the reaction evolved with total facial diastereoselectivity and the cis/trans ratio ranged between 1/4.2 and 1/9. Theoretical calculations indicate the reaction proceeds mainly by evolution of a planar free carbanion. The relative stability of the transition states predicts a trans/cis ratio that is in excellent agreement with the experimental results.

Asymmetric Nucleophilic Monofluorobenzylation of Carbonyl Compounds: Synthesis of Enantiopure vic‐Fluorohydrins and α‐Fluorobenzylketones

Asymmetric nucleophilic monofluoroalkylation of a broad range of aldehydes with an α-fluoro-γ-sulfinylbenzyl carbanion takes place with complete control of the facial selectivity at the carbanion and good to high anti-diastereoselectivity to give easily separable mixtures of two optically pure 1,2-fluorohydrin derivatives (up to 24:1 anti/syn). Separation and removal of the p-tolylsulfinyl group with tBuLi provides enantiomerically pure anti-1,2-disubstituted-1,2-fluorohydrins, whereas α-fluorobenzylketones can be obtained by desulfinylation of the mixture followed by pyridinium chlorochromate oxidation (one-pot process).

Stereoselective addition of alpha-methylsulfenyl benzyl carbanions to N-sulfinylketimines: asymmetric synthesis of alpha,alpha-dibranched beta-sulfanyl amines.

(R)- and (S)-N-sulfinylketimines react with the ortho-sulfinyl benzyl carbanion derived from (S)-1 affording epimeric mixtures at the benzylic carbon of alpha,alpha-dibranched beta-sulfanyl amines. The N-sulfinyl group completely controls the configuration at the quaternary carbon bonded to the nitrogen, whereas the C-sulfinyl group is responsible for the level of asymmetric induction. High stereoselectivity can be achieved when the configuration at the sulfur atoms of the reagents are opposite (matched pair). After a two-step desulfinylation process, this reaction provides a procedure for synthesizing diastereomerically pure syn-1,2-sulfanyl amines containing a chiral quaternary carbon adjacent to nitrogen.

Synthesis and photooxygenation of 2-thiofuran derivatives: a mild and direct access to O,S-dimethyl and O-methyl-S-phenyl thiomaleates

New 3-bromo-2-thio and 3-bromo-2,5-bis-(thio) furan derivatives have been synthesized and their synthetic potential has been assessed by their conversion into O,S-dimethyl and O-methyl-S-phenyl thiomaleates via methylene blue sensitized photooxygenation.

On the mechanism and diastereoselectivity of 2,3-dihydrobenzofuran formation from sulfinylbenzoquinones and 2-trimethylsilyloxyfuran

Abstract A mechanistic study of the reactions between 2-trimethylsilyloxyfuran 1 and (S S )-2-(arylsulfinyl)-1,4-benzoquinones 2a and 2b , giving rise to the diastereoselective formation of [3a S ,8b S ,S S ]-3a,8b-dihydro-7-hydroxy-8-(arylsulfinyl)furo[3,2- b ]benzofuran-2(3 H )-ones 3a and 3b , is reported. The detection and 1 H NMR characterization of several precursors of 3a and 3b accounts for a Michael-type initial reaction which dictates the final diastereoselection of the process. A significant improvement of the stereoselectivity (up to 96% de) in the formation of the tert -butylsulfinyl substituted derivative 3c was achieved by using 2-( tert -butylsulfinyl)-1,4-benzoquinone 2c as the starting quinone.

Synthesis and photooxygenation of (S)-p-tolylsulfinylfuran derivatives

Abstract The synthesis of different (S)-1,4-dicarbonyl-2-(p-tolylsulfinyl)-2-alkenes by photooxygenation of enantiomerically pure (S)-p-tolylsulfinylfurans is reported.

Stereoselective Alkylidenation of Ketones with 2-(p-Toluenesulfinyl)benzyl Iodide: Synthesis of Enantiomerically Pure Trisubstituted Epoxides

Alkylidenation of arylmethyl, dialkyl, and cyclic ketones with 2-( p-toluenesulfinyl)benzyl iodide in the presence of NaN(SiMe3)2 takes place with a high or complete control of the facial selectivity at the carbonyl group (up to 98% de) and the carbanion (>98% de), respectively, yielding mixtures of only two optically pure trisubstituted epoxides ( E/Z ratio ranges between 2:1 and >50:1). Removal of the p-tolylsulfinyl group with t-BuLi provides the corresponding (E)-3-phenyl-2,2-disubstituted epoxides without affecting their optical purity.

Synthesis of Optically Pure vic-Sulfanyl Amines Mediated by a Remote Sulfinyl Group

Enantiomerically pure syn-1,2-diaryl-1,2-sulfanylamine derivatives can be obtained in a completely stereoselective manner by reaction of the benzylcarbanion Li-(S)-1 with N-phenyl (or PMP)-arylidene aldimines and further desulfinylation with t-BuLi. Theoretical studies at the DFT (mPW1PW91) level with the CPCM model, by using the Gaussian09 program, provide a good explanation for the stereochemical results.