Sulfoxide, chiral vinyl 3 + 2 cycloaddition reactions

To control the stereochemistry of 1,3-dipolar cycloaddition reactions, chiral auxiliaries are introduced into either the dipole-part or dipolarophile. A recent monograph covers this topic extensively 70 therefore, only typical examples are presented here. Alkenes employed in asymmetric 1,3-cycloaddition can be divided into three main groups (1) chiral allylic alcohols, (2) chiral amines, and (3) chiral vinyl sulfoxides or vinylphosphine oxides.63c... 

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). 

The last problem associated with the use of the sulfinyl group as a chiral inductor in cycloaddition reactions is related to the endo/exo reactivity. From the available data, the endo directing power of the sulfinyl group is not large. The need to incorporate other functional groups into vinyl sulfoxides, thus increasing their dienophilic reactivity, decrees that the formation of mixtures is difficult to avoid in many cases as a consequence of the competition between the... 

Koizumi observed a diastereoselective cycloaddition between furan and chiral vinyl sulfoxides 6 [15]. While the analogous p-tolylsulfinyl acrylates were completely unreactive in this reaction, the 2-pyridyl (Py) substituent signifi-... 

The auxiliary-controlled, noncatalyzed [4 + 2] cycloaddition of homodienophiles has been thoroughly studied and the results are often compared with Lewis acid catalyzed reactions (see Section 1.6.1,1.1.2.2.2.). A very interesting version of dienophiles bearing a chiral auxiliary are chiral vinylic sulfoxides in which the chirality results from the dissymmetric sulfur atom. The first example studied is the Diels-Alder reaction of ( + )-(/ )-4-methylphenyl vinyl sulfoxide (1) with cyclopentadiene (2), in which four possible diastereomers 3-6 are obtained in an endojexo ratio of (5 + 6)/(3 + 4) 64 36. The diastereomers are further separated the (2 /J)-isomers (3 and 5) being favored. Desulfuration produces pure ( + )- or (-)-dehydronorcamphor. 

Dipolar cycloaddition of the nitrone 77 with the chiral vinyl sulfoxide affords an intermediate that is converted to (-F)-sedridine <97TA109>. A similar reaction of a chiral nitrone... 

The asymmetric induction on the 1,3-dipolar cycloaddition reaction of carbonyl ylides has also been studied using chiral dipolarophile. The Rh2(OAc)4-catalyzed reactions of o-(methoxycarbonyl)diazoacetophenone 89 with enantiomerically pure vinyl sulfoxides 103 afforded 4,10-epoxybenzo-[4,5]cyclohepta[l,2-c]furan-3,9-dione 105, in good or moderate yield with complete regioselectivity [113]. The endo stereoisomer 105a is favored with respect to the exo isomer 105b and interestingly, high diastereoselectivity and complete enantioselectivity have been achieved (Scheme 32). 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

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... 

Nitrones were the first as well as the most widely used dipoles in asymmetric cycloadditions. The first report on the use of enantiomerically pure vinylsulf-oxides as dipolarophiles was due to Koizumi et al. [153], who described in 1982 the reaction of (-R)-vinyl p-tolyl sulfoxide 1 with acyclic nitrones 191. The reactions required 20 h in refluxing benzene to be completed, yielding a mixture of only two compounds, 192 and 193 (Scheme 91). They exhibited identical endo or exo stereochemistry (which was not unequivocally assigned), deduced from the fact that their reduction yielded enantiomeric thioethers. The major component, 192, exhibits (S) configuration at C-3, determined by chemical correlation. The authors claim this paper [153] to be the first example of 1,3-dipolar cycloaddition using chiral dipolarophiles. 

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. 

Ketene equivalents have found widespread use as partners in Diels-Alder reactions for the construction of cyclic, fused, and bridged unsaturated ketones. However, ketene equivalents based on simple vinyl sulfoxides are poor dienophiles and show low levels of diastereocontrol. Recently, Aggarwal and colleagues reported that (l/ ,3/ )-2-methylene-l,3-dithiolane 1,3-dioxide (187) was a highly reactive and highly selective chiral ketene equivalent.116 Diels-Alder cycloaddition of this... 

Nitroethene and vinyl sulfoxides have also been employed as ketene equivalents. Nitroethene is an excellent dienophile and oxidation of the initial nitro-adduct gives the corresponding ketone. However, the thermal instability of nitroethene limits its appUcation to cycloadditions with reactive dienes. An attractive feature of vinyl sulfoxides as ketene equivalents is that they can be obtained in optically active form because of the chirality of the sulfoxide group, thus allowing enan-tioselective Diels-Alder reactions. Cycloaddition of p-tolyl vinyl sulfoxide with cyclopentadiene requires heat and gives a mixture of all four (two exo and two... 

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