Chiral sulfoxides Diels-Alder reaction

Another approach to asymmetric sulfoxide Diels-Alder reactions involves the stereoselective oxidation of a sulfide. Modena and coworkers [73] obtained sulfoxide-ester 9.74 (R = H) from chiral thiol 9.73 by addition to methyl propiolate and oxidation with MCPBA. The cycloaddition of 9.74 with cyclopentadiene at -5°C is highly selective due to the rigidification of the dienophile by internal hydrogen bonding (Figure 9.40). 

Arai Y., Koizumi T. Synthesis and Asymmetric Diels-Alder Reactions of Chiral. Alpha.,.Beta.-Unsaturated Sulfoxides Bearing a 2-Exo-Hydroxy-lO-Bornyl Group As an Efficient Ligand on the Sulfur Center Rev. Heteroat. Chem. 1992 6 202-217 Keywords allenic sulfoxide, a-sulfinylmaleate, a-sulfinylmaleimide, asymmetric synthesis, chiral unsaturated sulfoxides... 

The above-described structures are the main representatives of the family of nitrogen ligands, which cover a wide spectrum of activity and efficiency for catalytic C - C bond formations. To a lesser extent, amines or imines, associated with copper salts, and metalloporphyrins led to good catalysts for cyclo-propanation. Interestingly, sulfinylimine ligands, with the chirality provided solely by the sulfoxide moieties, have been also used as copper-chelates for the asymmetric Diels-Alder reaction. Amide derivatives (or pyridylamides) also proved their efficiency for the Tsuji-Trost reaction. 

Arai and coworkers197 reported the utilization of a chiral pyrrole sulfoxide as a chiral auxiliary in the asymmetric Diels-Alder reactions of its /V-cinnamoyl and /V-crotonyl derivatives 313 with cyclopentadiene which gave 314-317 (equation 87). The results have been summarized in Table 18. The yield as well as the endo/exo selectivity and the de proved to depend on the type and amount of Lewis acid used. 

In a rather elegant approach towards colombiasin A (36) Flynn et al. [47] would access the tetracyclic carbon skeleton through an enantioselective intermolecular Diels-Alder sulfoxide elimination-intramolecular Diels-Alder (DA-E-IMDA) sequence between double-diene 166 and quinone 167 (Scheme 26). A key element of the proposed approach would be the chiral sulfoxy group in 167 which controls both the regio and facial selectivity of the intermolecular Diels-Alder reaction and eliminates generation of the dienophile for the IMDA reaction. 

Chiral bis-sulfoxides with a C2 symmetry axis can be readily prepared from the known (W)-methyl p-tolyl sulfoxide and commercially available methyl (S)-p-toluenesulfinate. Such chiral ligands are very attractive because of their easy synthesis and their ready availability in both enantiomers from inexpensive starting materials. Their complexes with Fel3 are shown to be good chiral catalysts for asymmetric Diels-Alder reactions [48] (Eq. 8A.26). 

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... 

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... 

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). 

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... 

Complete chirality transfer has been achieved in syntheses of 1-amino-2-hydroxy-3-alkenyl derivatives from (Z)-/ -substituted ally] sulfoxides, due to 1,3-allylic strain as an additional controlling factor. Stereochemically homogeneous 3,6-dihydro-l,2-thiazine oxides are easily obtained by hetero Diels-Alder reaction of A-sulfinyl carbamates and ( , )-2,4-hexadienes37 (see Section D.1.6.1.1.1.1.2.2). 

The chirality at sulfur also confers to (Z)-3-carbonylmenthoxy vinyl sulfoxides a useful topological bias which will be discussed in context with asymmetric Diels-Alder reactions (Section 4.1.6.2.1 (vi)). 

Titanium-pillared montmorillonites (Ti-PILC) modified with tartrates were described as heterogeneous Sharpless epoxidation catalysts [33] as well as for the oxidation of aromatic sulfides [34]. Metal oxides modified with histamine showed modest efficiencies for the kinetic resolution of activated amino acid esters (kj /k5 2) [35]. Silica or alumina treated with diethylaluminium chloride and menthol catalyzed the Diels-Alder reaction between cylopentadiene and methacrolein with modest enantioselectivities of up to 31% ee [36]. ZeoHte HY, modified with chiral sulfoxides had remarkable selectivities for the kinetic resolution of 2-butanol (k /kj =39) but unfortunately the catalyst is not very stable... 

Sulfoxide, sulfinate and sulfonate are used as activators of acetylenic or vinyl units. Several a, P unsaturated synthons, namely acetylenic sulfoxide (1), vinyl sulfoxide (2), acetylenic sulfinate (3), acetylenic sulfonate (4), and l-propene-l,3-sultone (5) are developed. Their applications in Diels-Alder reactions, heterocycle and alkaloid syntheses are also investigated. For the chiral acetylenic sulfoxide, the sulfoxide moiety not only enables chemical activation of the acetylene unit, it can also induce stereochemical control at the adjacent carbon centers to achieve enantioselective synthesis. 

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