Chiral sulfinyl groups

The first report on the addition of carbanions a-substituted by a chiral sulfinyl group to carbonyl functions described the reaction with symmetrical ketones3. It was found that meta-lation of ( + )-(S)-(methylsulfinylmethyl)benzene followed by quenching with acetone gives a mixture of diastereomeric /i-hydroxysulfoxides in a 15 1 ratio. This ratio depends on the presence or absence of extra lithium salts i.c., the source of the mcthyllithium used in deprotonation67. 

It has been found that F-Teda BF4 (6) transforms chiral and optically pure ft-oxo sulfoxides into the corresponding a-fluoro-substituted compounds 30 without affecting the chiral sulfinyl group.106... 

Chiral sulfoximines liganded to copper(II) give highly enantioselective vinylogous Mukaiyama-type aldol reactions under mild conditions.137 A chiral sulfinyl group has been used to achieve 1,5- and 1,6-asymmetric induction in Mukaiyama aldols, using Yb(OTf)3 catalysis.138... 

Sulfinyl dienes and vinyl sulfoxides have rarely been used in asymmetric hete-ro-Diels-Alder reactions [145]. The first example was reported in 1992 and describes an intramolecular cycloaddition using a heterodiene bearing a chiral sulfinyl group [146a]. In this paper, the conversion of a-p-tolylsulfinyl a,ft-unsaturated ketone 176 (prepared by Knoevenagel reaction of 3-methylcitronellal and (S)-p-toluenesulfinylacetone) into the hetero-Diels-Alder adducts 177... 

Reactions of 3,5-dichloro-2,4,6-trimethyl benzonitrile oxide 241 with fluoro-methyl substituted alkenes 242, bearing a chiral sulfinyl group at -position of the double bond, afford diastereoisomeric 4,5-dihydroisoxazoles 243 and 244 [180] with a stereoselectivity lower than 2 1 (Scheme 110). The authors conclude that the efficiency of allyl sulfoxides to control diastereoselectivity of 1,3-dipolar cycloadditions with nitrile oxides is lower than that of vinyl sulfoxides. 

Reduction of sulfoxides to thioethers.1 Use of hydrogen halides for this reduction was first reported in 1909 and is still a viable method. This reduction has assumed importance since chiral sulfinyl groups are valuable in asymmetric syntheses and are eliminated in two steps reduction to the ether followed by catalytic hydrogenation or metal/ammonia reduction. The first step can now be carried out with several reagents, as shown by this comprehensive review (349 references). 

The observed change in stereoselectivity can be rationalized by consideration of the conformation of the 2-(arylsulfinyl)-2-cyclopentenone (24) (Fig. 3). The sul-finyl and carbonyl moieties are normally arranged in an anti periplanar orientation (27). The bulky aromatic substituent on the chiral sulfinyl group shields one face of the alkene and thereby controls the facial selectivity of the reaction. In the presence of the Lewis acid the sulfinyl and carbonyl moieties are locked in a syn orientation (28) as a result of chelation between the two moieties and the metal. Thus, the opposite face of the alkene is shielded and (3-addition results in the other diastereoisomer being formed. 

The intramolecular alkylation would occur from the downward side of the chiral sulfinyl group, opposite the bulky p-tolyl group. 

Asymmetric [4 + 2] cycloadditions of an optically active diene, or dienophile with chiral sulfinyl groups, with a quaternary sulfur center have succeeded in the LiC104-CH2CI2 medium. When chiral dienophile 66 and CP were subjected to cyclization, neither the endotexo ratio nor the enantiofacial selectivity of endo adducts was high [83], In the reaction of chiral diene 67 with MA, the best catalyst was LiC104-CH2CI2 this gave only endo isomers endo-6Sa and endo-6Sb in 70 % yield in the ratio of 96 4, presumably via TS-2 (Sch. 35) [84]. 

In 1972, Tsuchihashi disclosed that the carbanion (28 Ar = p-tolyl), generated from (/ )-methyl p-tolyl sulfoxide with lithium diethylamide, adds to benzaldehyde or a-tetialone to give an adduct (29) in a dia-stereomeric ratio of 50 50 or 64 36, respectively. Additions of this carbanion to various unsymmetrical ketones are also reported to be poorly diastereoselective (for example, EtCOMe 50 50, Bu COMe 55 45, Bu COPh 70 30). Note that in the case of Ar = 2-pyridyl a chiral sulfinyl group increases the asymmetric induction observed in the addition of the corresponding carbanion to carbonyl compounds (PhCHO 80 20, R-C9H19CHO 70 30). Since diastereomer pairs of (29) are separable, chromatographic separation followed by reductive desulfurization with Raney Ni provides a method for obtaining optically active alcohols (30 Scheme 9). 

Lewis acid-catalysed cleavage of the bicyclic acetal (8) with allyltrimethylsilane occurs with 1,3- and 1,6- asymmetric induction arising from the chiral sulfinyl group. The resulting chiral 2,2,5-trisubstituted tetrahydropyran was used to synthesise (-) malyngolide, a marine antibiotic <97CC1755>. 

Stereochemical Control Element on the Pyrone Diene. Early work in our group showed that the chiral sulfinyl group of pyrone 51 provides a measure of stereochemical control in Diels-Alder reactions/ Diastereomeric excesses as high as 76% are obtained. Unfortunately, subsequent efforts to prepare enantiopure 51 have been unsuccessful. 

C. CHIRAL LIGANDS CONTAINING CHIRAL SULFINYL GROUPS... 

Chiral oxazoline ligands 24a,bearing a chiral sulfinyl group provided enantiose-lectivity of (5)-2 with 88% or 55% ee, respectively, in the Pd-catalyzed alkylation of 1 with dimethyl malonate using [Pd(7r-allyl)Cl]2, BSA, and KOAc in dichloromethane... 

Scheme 7.20 Diastereoselective Mizoroki-Heck arylation directed by a chiral sulfinyl group.

Scheme 11.49 Pd(0)/dppe-catalyzed diastereoselective rearrangement of dienyl cyclopropanes hearing chiral sulfinyl group.

As described in Sect. II.2.4, organosulfur functionality such as sulfenyl and sulfinyl groups can directly participate in Pd-catalyzed reactions, normally by coordination of the sulfinyl sulfur atom to palladium in the case of sulfinyl groups. Few reports have been published so far concerning nucleophilic substitution reactions of 7r-allylpalladium complexes bearing chiral sulfinyl groups. 

In general, chiral sulfinyl groups in allylic systems can participate in the Pd-catalyzed reactions, if sterically possible, by the coordinahon of the sulfinyl sulfur atoms to TT-allylpalladium complexes generated. When the steric requirement for the coordination is rather severe, the effect of chiral sulfinyl groups is simply understandable, without the direct participation, by the steric bulk of the sufinyl substituents. 

The plausible mechanism of asymmetric induction is proposed (Scheme 2). The palladium catalyst reacts from the sterically less crowded downward direchon of the lone pair side of the chiral sulfinyl group in the conformationally most stable form of (5s)-l with syn-coplanality between the sulfinyl-oxygen bond and the carbon-carbon double bond of the chiral vinyl sulfoxide, forming 3. Based on the stereochemistry of the product, the... 

In the case of (/ s)-(Z)-9, the direct participation of the chiral sulfinyl group to the palladium should be crucial the initially formed rr-allylpaUadium complex (i s)-(Z)-13 is stabilized by the coordination of the sulfinyl sulfur atom to the palladium, forming 14 with the retained (Z)-configuration of the olefin. The subsequent intramolecular nucleophilic substitution from the opposite side of the palladium provides (5,i s)-(Z)-ll in a highly stereoselective fashion (Scheme 5). 

Chiral sulfinyl sulfur atoms can coordinate to palladium in Pd-catalyzed reactions of allylic systems bearing chiral sulfinyl groups at the appropriate site, if the steric environment allows the sulfinyl sulfur atoms to access the n -allylpalladium complexes generated for participation by the coordination. 

Cyclic (hetero- and carbocyclic) vinyl sulfoxides have been prepared by a tandem Michael addition/Homer olefination reaction of a-phosphorylvinyl sulfoxides and carbonyl compounds bearing a nucleophilic center. Using optically active a-phosphorylvinyl sulfoxides a series of enantiomeric cyclic vinyl sulfoxides in which the chiral sulfinyl group is bonded to a chromene, pyrrazolyne, quinoline or cyclopen-tene ring, has been obtained. The H-W-E reaction of aldehydes with sulfinimine-derived 3-oxo pyrrolidine phosphonates (228) represents a new method for the asymmetric synthesis of ring-functionalized cw-2,5-disubstituted 3-oxo pyrrolidines (229) (Scheme 90). ... 

A series of highly selective reactions have been reported by Guijarro et al., where a chiral sulfinyl group directs the ATH of an imine, using either an asymmetric catalyst or a racemic one (Fig. 49). Using cis-aminoindanol, very selective syntheses of amines are possible [162-164], and imine formation can be accelerated with microwave irradiation. 

Carreno and Urbano et al. examined nucleophilic additions of alkylaluminum reagents to benzaldehyde 24 bearing a chiral sulfinyl group (Scheme 23) [41]. The effective association between aluminum atom and oxygen atom of sulfinyl moiety could be required to determine the stereochemical outcome of the alkylated products 25. 

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