Sulfur stereoselective cycloadditions

These A-sulfinyl Diels-Alder reactions are also highly stereoselective, giving products of syn addition to the 1,3-diene. The same holds true for the sulfur diimide cycloadditions . The stereoselectivity with respect to the dienophile is not very well known because the stereochemistry of sulfur in the starting A-sulfinyl dienophile and in the resulting thiazine derivatives has usually not been determined. A representative sample of the stereoselective preparation of 3,6-dihydrothiazine 1-oxides and 1-imines is shown in Scheme 34 <84JA786i, 84JA7867>. 

As can be seen from some of the examples cited above, a single or predominant sulfur stereoisomer often results from the cycloaddition process, but sometimes mixtures of sulfur epimers are produced. In many of these cycloadducts the configuration at sulfur has not been determined, and thus not enough data are currently available to clarify what factors control the configuration established at sulfur. These cycloadditions do show the usual Diels-Alder syn stereoselectivity with respect to the 1,3-diene component. 

Two attractive routes to thiolene oxide and dioxide are the diene-SO104 and diene-S02298 cycloadditions, respectively. These cycloadditions are highly stereoselective at both carbons of the diene systems and at sulfur (see equation 62 for specifics) which, in the case of sulfoxide formation, proceed via attack of triplet SO on the diene. Equation 112 shows an example of such a cycloaddition104. The overall yields are significantly improved by running the cycloadditions in the absence of oxygen and by the use of excess diene. 

Hassner and coworkers have developed a one-pot tandem consecutive 1,4-addition intramolecular cycloaddition strategy for the construction of five- and six-membered heterocycles and carbocycles. Because nitroalkenes are good Michael acceptors for carbon, sulfur, oxygen, and nitrogen nucleophiles (see Section 4.1 on the Michael reaction), subsequent intramolecular silyl nitronate cycloaddition (ISOC) or intramolecular nitrile oxide cycloaddition (INOC) provides one-pot synthesis of fused isoxazolines (Scheme 8.26). The ISOC route is generally better than INOC route regarding stereoselectivity and generality. 

The reaction of (trialkylsilyl)vinylketenes with nucleophilic carbenoid reagents, such as sulfur ylides and diazo compounds, has been used for synthesis of substituted cyclopentenones by stereoselective 4 + 1-annulation (Scheme 12). The strategy relies on the remarkable ability of silyl substituents to stabilize ketenes and suppress their tendency to undergo dimerization and 2 - - 2-cycloaddition. 

New possibilities were reported by Kagan [529], who observed that vinyl sulfoxides could be activated for the Diels-Alder reaction by alkylation into vinyl sulfonium salts. A number of cycloadditions of these salts occurred then under mild conditions and with high stereoselectivities. The results could be particularly striking, as in the case of the low-temperature (-78°C) reaction of ethoxy p-tolyl vinyl sulfonium tetrafluoroborate (2) with cyclopentadiene. Only the endo isomer (3) was formed with a de. higher than 99%. and isolated in a 62% yield after transformation of the sulfonium adduct into a sulfoxide (with inversion at sulfur) by sodium hydroxide. 

The silver acetate-promoted 1,3-dipolar cycloaddition of nitrilimines with 3(/f )-pheny]-4(A )-cinnamoyl-2-azetidinone produced the major adduct, 4-(4,5-dihydro- (g) pyrazol-5-yl)carbonyl-2-azetidinones, with high stereoselectivity.70 The 1,3-dipolar cycloadditions of substituted 2,7-dime(liyl-3-thioxo-3,4,5,6-ici.rahydro-2//- 1,2,41 triazepin-5-one with iV-aryl-C-ethoxycarbonylnitrilimines are highly chemoselective, where the sulfur atom of the dipolarophile interacts with the carbon atom of the dipole.71 The enantioselective 1,3-dipolar cycloaddition of nitrile imines with electron deficient acceptors produces dihydropyrazoles in the presence of 10 mol% of chiral Lewis acid catalyst.72... 

A comparative study between the Patemb-Biichi reaction of aromatic aldehydes with silyl 0,0-ketene acetals, 109, and 0,A-ketene acetals, 111, has highlighted sulfur atom effects on both regio- and stereoselectivities (Scheme 21) <1996TL5901, 1998J(P1)3253, 1998J(P 1)3261, 2000JA4005>. Cycloadditions with 109 were not stereoselective and gave 2-siloxyoxetanes 110. By contrast, reactions with 111 favored the formation of tram-3-siloxyoxetanes, 112. 

A reaction closely related to the [2 + 2] cycloaddition of thiocarbonyl S.S-dioxides is the addition of sulfur trioxide-dioxane complex to alkenes. This occurs stereoselectively and from (Z)- and (E)-2-butene the corresponding cis- and /ra .s -3,4-dimethyl-1,2-oxathietane 1,1-dioxides 11 are obtained121. 

Two general classes of V-sulfinyl compounds have been employed as dienophiles. The most widely utilized type are N-sulfinyl species (115), formally monoimines of sulfur dioxide, which produce 3,6-di-hydrothiazine 1-oxides (116) (Scheme 14) upon cycloaddition. - -phe analogous bis-imines of sulfur dioxide (117) have also been used upon occasion as dienophiles to yield the 3,6-dihydrothiazine 1-imines (118). Both processes show excellent regioselectivity and are syn stereoselective with respect to the... 

Stereoselective Diels-Alder reactions have been reported in several cases. Enantioselective Diels-Alder reactions of l-phenoxycarbonyl-l,2-dihydropyridine with 1-alkylated acryloyl-pyrazolidin-3-ones using a chiral cationic palla-dium-phophinooxazolidine catalyst afforded chiral isoquinuclidines with excellent enantioselectivity <2005TL5677>. Bismuth(lll) chloride-mediated diasteroselective intramolecular [4-f2] cycloaddition reactions of A-allyl derivatives of pyrazole aldehydes led to fused sulfur-containing pyrazole heterocycles <2003SC3063>. A highly diastereoselective intramolecular hetero-Diels-Alder approach toward tetracyclic pyrazoles from 5-(3-methyl-2-butenylthio)-3-methyl-l-phenyl-4-pyrazolecarboxaldehyde has been reported <1997SL1155>. 

Since the Diels-Alder cycloadditions used to prepare various dihy-drothiazine imines generally produced mixtures of sulfur epimers, it was desirable to find a procedure to also convert the unreactive adducts to the vicinal diamines. It was discovered that adducts 60 rearranged thermally by a novel [2,3]-sigmatropic process to afford thiadiazolidines 62 stereoselectively (Scheme 1-XV). Reduction of 62 with sodium borohy-dride yielded the -threo vicinal diamine derivative 57. Similarly, unreactive adducts 61 cleanly gave thiadiazolidines 63 on heating, which could be converted to E-erythro vicinal diamines 59. This methodology thus allows both sulfur epimers from ( , )-2,4-hexadiene to be converted to the -threo product, and the epimers from ( ,Z)-2,4-hexadiene to be used to prepare the -erythro series of compounds. 

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