A-Sulfenyl aldehydes

Protected sulfenylation reagents (Lg-S-Pg) a-sulfenylate aldehydes, using steri- cally encumbered chiral pyrrolidines as enantioselective organocatalysts.298... 

Dicarbonyl compounds. The adducts (2) of the anion (1) of meth-oxy(phenylthio)methane and aldehydes (12, 316) are converted into a-sulfenyl aldehydes (3) on treatment with methanesulfonyl chloride and triethylamine (1 1). Reaction of 3 with a Wittig or Wittig-Horner reagent followed by isomerization... 

The alkylation of SAMP/RAMP hydrazones with heteroelectrophiles leads to enantiomerically pure a-silyl aldehydes and ketones (eq 15), a-sulfenyl aldehydes and ketones (eq 16), and a-hydroxy aldehydes and ketones (eq 17). ... 

Poli G, Belvisi L, Manzoni L, Scolastico C. First asymmetric synthesis of enantiopure a-sulfenyl dithioacetals and a-sulfenyl aldehydes./. Org. Chem. 1993 58 3165-3168. 

Rearrangement of Thioacetals to Aldehydes. Sato et al. reported the rearrangement of a-hydroxy thioacetals to a-sulfenyl aldehydes (eq 34). The thioacetals are prepared by the addition of the anion of methoxy(phenylthio)methane to aldehydes and ketones. This reaction is general for alkyl, allyl, and aromatic carbonyl compounds. 

It should be noted that the more sterically demanding a,a-disubstituted aldehydes could be efficiently sulfenylated when the same catalyst was used, even if with lower enantiomeric excess (61% ee). 

A noteworthy improvement comes from the use of ligand systems which are themselves optically active." This is die case of the complex (150), shown in Scheme 21, that is prepared from a sulfenylated norephedrine (149). The results reported for the in situ reactions of (150) with various aldehydes (Scheme 21) are summarized in Table 14." Nothing is reported concerning the mechanism of the en-antioselecdve addition, since the absolute configuration of the asymmetrically substituted Ti atom is not known. 

Jorgensen and co-workers reported the enantioselective a-sulfenylation of aldehydes catalyzed by 6b (Equation 10.16) [34]. Hayashi et al. reported the 1,4-addition reaction of acetaldehyde with nitrostyrene in the presence of 6a (Scheme 10.17) [35]. The introduction of a siloxy group into proline increased its catalytic activity, thus allowing for a decrease in catalyst load and reaction time without compromising the... 

The addition of thiyi radicals can be performed in the presence of oxygen, the process being known as cooxidation. This is an attractive method to generate peroxy radicals through the capture of the yff-sulfenyl radical, and it can be electrochemi-cally initiated. As shown in Scheme 4, the products are a-(phenylthio)aldehydes starting from either alkenyl sulfides or alkynes [24] j5-hydroxysulfoxides can also be prepared [25] (Eq. 8). 

Sulfenylation. Acylsilanes and aldehydes undergo acid-catalyzed a-sulfenylation. Ketones give low yields under the same condsitions. 

Chiral 2-sulfenylated aldehydes. Alkylation of the hydrazone derived from methylthioacetaldehyde, followed by ozonolytic cleavage of the chiral auxiliary constitutes a route to this class of compounds. 

Heterofunctionalisation of carbonyl compounds in the a-position has become an important facet of oiganocatalytic enamine-mediated reactions. In 2005, the Jorgensen group described asymmetric a-sulfenylation of aliphatic aldehydes using TMS-protected prolinol catalysts. The best sulfenylating agent was M-benzylsulfanyl-1,2,4-triazole. Other catalysts, such as proline, prolinol, prolinamide or other secondary amide were less effective. The catalyst with bulkier aromatic groups (C2a) afforded the most enantioselective reaction (Scheme 8.39). 

Hiemstra and co-workers described a similar process with the use of A(-sulfenyl tryptamines, whereby it was theorized that the sulfenyl substituent would not only stabilize the intermediate iminium ion but also have the benefit of being removed easily [41]. Using another chiral phosphoric acid 128, Hiemstra demonstrated the Pictet-Spengler reaction using (triphenyl)methylsulfenyl tryptamine 127 and a variety of aldehydes (Scheme 1.31). 

SCHEME 14.23. Enantioselective a-sulfenylation of aldehydes and synthetic applications. 

The diarylprolinol silyl ether system was initially applied for the asymmetric a-sulfenylation of aldehydes. Since then, it has proven its usefulness in combination with a large number of heteroatom- and carbon-based electrophiles for asymmetric a-functionalizations of aldehydes (Scheme 2.3) [2, 3, 9]. 

In 2005, J0rgensen and co-workers introduced 1-benzyl-sulfanyl[ 1,2,4] triazole 416 as an electrophilic sulfur source for the catalytic enantioselective a-sulfenylation of aldehydes (Scheme 46.47). ° The products 418 were obtained in high yields and excellent enantioselectivities, and more importantly, these products obtained by enamine catalysis were not racemized by the action of a chiral pyrrolidine catalyst 417. 

Youn J, Hermann R, Ugi I. Synthesis of enantiomerically enriched a-sulfenylated ketones and aldehydes. Synthesis 1987 159-161. 

Enders D, Schafer T, Mies W. Enantioselective synthesis of a-sulfenylated ketones and aldehydes via a-thiolation of metalated SAMP/RAMP hydrazones. Tetrahedron 1998 54 10239-12052. 

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