Chiral vinyl sulfoxide

Verify, by making molecular models, that the bonds to sulfur are arranged in a trigonal pyramidal geometry in sulfoxides and in a tetrahedral geometry in sulfones. Is phenyl vinyl sulfoxide chiral What about phenyl vinyl sulfone ... 

To control the stereochemistry of 1,3-dipolar cycloaddidon reacdons, chiral auxiliaries are introduced into either the dipole-part or dipolarophile A recent monograph covers this topic extensively ° therefore, only typical examples are presented here. Alkenes employed in asymmetric 1,3-cycloaddidon can be divided into three main groups (1) chiral allyhc alcohols, f2 chiral amines, and Hi chiral vinyl sulfoxides or vinylphosphine oxides. 

Besides simple alkyl-substituted sulfoxides, (a-chloroalkyl)sulfoxides have been used as reagents for diastereoselective addition reactions. Thus, a synthesis of enantiomerically pure 2-hydroxy carboxylates is based on the addition of (-)-l-[(l-chlorobutyl)sulfinyl]-4-methyl-benzene (10) to aldehydes433. The sulfoxide, optically pure with respect to the sulfoxide chirality but a mixture of diastereomers with respect to the a-sulfinyl carbon, can be readily deprotonated at — 55 °C. Subsequent addition to aldehydes afforded a mixture of the diastereomers 11A and 11B. Although the diastereoselectivity of the addition reaction is very low, the diastereomers are easily separated by flash chromatography. Thermal elimination of the sulfinyl group in refluxing xylene cleanly afforded the vinyl chlorides 12 A/12B in high chemical yield as a mixture of E- and Z-isomers. After ozonolysis in ethanol, followed by reductive workup, enantiomerically pure ethyl a-hydroxycarboxylates were obtained. 

G. H. Posner, Addition of Organometallic Reagents to Chiral Vinyl Sulfoxides in Asymmetric Synthesis. J. D. Morrison, Ed. Vol. 2, p. 225, Academic, New York 1983. 

To understand the interdependence of the creation of the two chiral centers relative to each other and to the sulfoxide, monosubstituted vinyl sulfoxides (S)-53 and (S)-54 were prepared and reduced with BH3-THF under the same conditions (Scheme 5.19). Both the 2- and 3-phenyl substituted substrates gave the chiral products 54 and 55 with complete stereo specificities dictated by the configuration of the starting sulfoxides. These results again were unexpected and indicated that both hydrogens were delivered solely directed by the chiral sulfoxide. This was not consistent with the mechanism in which the chirality of the initially formed chiral center at the 3-postion dictates the chirality of the subsequently formed chiral center at the 2-position. 

Various chiral dipolarophiles have been used in the asymmetric synthesis of hexahydro-isoxazolo[2,3- ]pyridines. Examples include // / -2-methylcnc-l, 3-dithiolane 1,3-dioxide 83 <1998JOC3481>, chiral vinyl sulfoxide 85 <1997TA109>, or chiral dioxolanes <2001TA1747> (Scheme 27). 

Bicyclo-y-butyrolactones.1 The reaction of ketenes with chiral vinyl sulfoxides to obtain optically pure -y-arylsulfanylbutyrolactones (12,177) can be extended to a synthesis of bicyclic butyrolactones. Thus the arylsulfanyl group of 1 undergoes... 

Another type of chiral alkene applied in 1,3-dipolar cycloadditions are vinyl groups attached to chiral phosphine oxides or sulfoxides. Brandi et al. (150,151) used chiral vinyl phosphine oxide derivatives as alkenes in 1,3-dipolar cycloadditions with chiral nitrones. This group also studied reactions of achiral nitrones with chiral vinyl phosphine oxide derivatives. Using this type of substrate, fair endo/exo-selectivities were obtained. In reactions involving optically pure vinyl phosphine oxides, diastereofacial selectivities of up to 42% de were obtained. Chiral vinyl... 

Fluoro-substituted chiral vinyl sulfoxides such as 103 have been used in 1,3-dipolar cycloadditions with various benzonitrile oxides (Scheme 12.34) (158). The reaction proceeded slowly at room temperature, however, after 5-10 days the isoxazoline (104) was obtained with excellent de in good yield. In some cases, the product tends to eliminate the 5-methoxy substituent of the isoxazoline, thus, after loss of two chiral centers, an isoxazole is obtained (158,159). Other chiral suMnyl derivatives have also been used in 1,3-dipolar cycloadditions with nitrile oxides (160,161), and in one case a racemic vinyl phosphine was used in reactions with various nitrile oxides, but with moderate selectivities (151). 

Diastereoselective reactions of azomethine ylides with chiral vinyl sulfoxides have also been conducted (Scheme 12.35) (162-164). The 1,3-dipolar cycloaddition of (R)s-p-tolyl vinyl sulfoxide (106) with l-methyl-3-oxidopyridinum (105) gave three of the four possible diastereomers, and one of these isomers 107 was used for the enantioselective synthesis of the (75)-(—)-2a-tropanol 108 (162). 

Another application of additions to chiral vinylic sulfoxides constitutes the Hantzsch-type reaction of methyl 3-aminocrotonate with compound (109), yielding the dihydropyridine derivative (110) as a single... 

During the past two decades, the asymmetric Diels-Alder reaction has become one of the most powerful tools in asymmetric synthesis as a result of its capacity to create up to four chiral centers in one step, often in a highly stereoselective manner. In the following sections, recent advances in this area using vinyl sulfoxide and vinyl sulfone dienophiles will be considered. It should be noted that, although beyond the scope of this review, many asymmetric Diels-Alder reactions of chiral sulfinyl-1,3-dienes have been reported.111... 

In the past decade Carretero et al. have made significant advances in this area using a variety of activated chiral vinyl sulfoxides containing either one, two, or three additional activating groups.97 The Diels-Alder cycloadditions of several dienophiles based on the 2-sulfmylcyclopentenone skeleton have been investigated... 

The Diels-Alder reactions of a variety of acyclic chiral vinyl sulfoxide dienophiles, bearing additional electron-withdrawing groups at the double bond, have been investigated (Fig. 6). The asymmetric Diels-Alder reaction of enantiopure (5)-benzyl 2-p-tolylsulfinylacrylate (167) with furan, under high pressure, afforded mainly a 2 1 mixture of endo adducts. These were then stereoselectively transformed into (+)-shikimic acid and (+)-5-epi -shikimic acid.101 However, the poor control of the endo/exo selectivity and the low reactivity were the two main problems restricting the general synthetic usefulness of such a-sulfinylacrylate dienophiles. 

Carmen Carreno and co-workers have investigated Diels-Alder reactions of a wide variety of benzoquinone-based chiral vinyl sulfoxide dienophiles (Fig. 9). 

Enantiospecific addition to chiral vinyl sulfoxides. The cycloaddition of dichloroketene (11, 169-17(1) to optically pure (R)- or (S)-l-cyclohexenyl tolyl sulfoxides (1) leads to optically pure y-butyrolactoncs (2) with complete cnantiospecificity at the two chiral centers. A third hiral ew-center is introduced in the addition of monochloroketene. 

Cycloaddition with nitrile oxides is also efficient with trisubstituted enol ethers and enolates. With fluoro-substituted chiral vinyl sulfoxides 10. cycloadditions performed with aryl chloroaldoximes, at room temperature in carbon tetrachloride in the presence of triethylaminc, are slow but give the homochiral dihydroisoxazoles 11 with high regio- and diastereoselectivity. ... 

Chiral vinyl sulfoxides have been prepared by a Wittig Horner reaction of chiral (R)- or (.Si-dimethyl (4-tolylsulfinyl)methanephosphonate with carbonyl compounds3-66,67. For acyclic systems reprotonation of the anions from vinyl sulfoxides gave a mixture of E- and Z-isomers3, whereas isomerization of an exocyclic double bond in a ring system provided access to chiral aryl 1-cycloalkenylmethyl sulfoxides66-67. 

Chiral vinyl sulfoxides can also be prepared Horner-Emmons reaction of carbonyl compounds with a-phosphoryl sulfoxides which are obtained from lithiated dimethyl methylphosphonate and (-)-menthyl (S)-p-toluenesulfinate (eq 8). However, this reaction applied to carbonyl compounds often gives a mixture of the (E) and (Z) isomers of the vinylic sulfoxide. 

Chiral vinyl sulfoxides have been coupled to aryl iodides to give a chiral allylic aryl compounds (C=C-CH2—Ar), in a three-step procedure with good enantio-selectivity. ... 

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