Sulfoxides chiral route

An impressive new route to enantiopure syn- and anti- 1,2-diols involves sequential diastereoselective DIBAL reduction of oxalyl-di(/V-iucthyl-/V-methoxyainide) following conversion to a corresponding intermediate / -keto sulfoxide a route that involved control of both reductions by the chiral sulfoxide auxiliary.253 Comparison of / -hydroxy ketone systems with die y-sulfoxide-/ -keto systems used here showed this to be die first example of such asymmetric induction by a y-sulfoxide substituent. 

Two formal syntheses of (-)- [80] and (+)-kumausallene [81] followed this route and relied on the enantioselective preparation of the 2,6-dioxabicyclo[3.3.0]octane core 69 starting from diethyl tartrate or an appropriate chiral sulfoxide. In contrast, Evans et al. [82] used a distinct biomimetic approach in their enantioselective synthesis of the natural product (-)-62 (Scheme 18.23). 

An attractive route to chiral sulfoxides is based on asymmetric oxidation of unsymmetrical sulfides by means of chiral oxidizing reagents. The first asymmetric oxidation of sulfides with optically active pera-cids (eq. [1]) has been independently described in 1960 by two groups headed by Montanan (36) in Italy and by Balenovic (37) in... 

The first indication of the chirality of sulfuranes was provided by the X-ray analysis of spirosulfurane 176 (192). This work clearly demonstrated the presence of enantiomeric pairs of 176 in the crystal lattice. In 1975, the optically active chlorosulfurane 177, the first example of an optically active tetracoordinate sulfurane, was synthesized by Martin and Balthazor (194,195) by the route indicated in Scheme 15. Reaction of (-)-(5)-menthyl benzenesulfinate 178 with the protected Grignard reagent 179 gave the corresponding sulfoxide alcohol (-)-(5>180 which was cyclized to the chlorosul-... 

Review on some routes to chiral sulfoxides with very high enantiomeric excess H. B. Kagan, F. Rebiere, Synlett 1990, 643. 

Chiral sulfoxides have emerged as versatile building blocks and chiral auxiliaries in the asymmetric synthesis of pharmaceutical products. The asymmetric oxidation of prochiral sulfides with chiral metal complexes has become one of the most effective routes to obtain these chiral sulfoxides.We have recently developed a new heterogeneous catalytic system (WO3-30% H2O2) which efficiently catalyzes both the asymmetric oxidation of a variety of thioethers (1) and the kinetic resolution of racemic sulfoxides (3), when used in the presence of cinchona alkaloids such as hydroquinidine 2,5-diphenyl-4,6-pyrimidinediyl diether [(DHQD)2-PYR], Optically active sulfoxides (2) are produced in high yields and with good enantioselectivities (Figure 9.3). ... 

Asymmetric oxidation of prochiral sulfides is one of the most effective routes for the preparation of chiral sulfoxides. These latter molecules attract great interest, as they are useful synthons for some drugs. They can also be used as chiral auxiliaries due to their configurational stability. The oxidation can be performed by using complexes... 

Complexes Containing Chiral Sulfoxides. The blue solutions obtained by refluxing RuCl3 3H20 in polar solvents under H2 have provided a useful route to Ru(II) complexes (43,44). As described in the experimental section, treatment of such methanolic solutions with monodentate sulfoxides (Rudigand = 1 2) yielded the trimeric [RuC L ta species (where L = chiral ligands MBMSO and MPTSO) and a polymeric complex [RuC L ln (where L is racemic methyl phenyl sulfoxide). 

Addition to allylic mesylates.6 Conjugate addition of organocyanocuprates to acyclic allylic mesylates substituted at the P-position with a chiral sulfoxide group involves an SN2 -substitution with high Z/E stereoselectivity and high asymmetric induction. This reaction provides a route to chiral trisubstituted vinyl sulfoxides. 

Sulfilimines and sulfoximines are useful synthetic building blocks for chiral ligands and pseudopeptides. Compared to other preparation methods, the direct imination of corresponding sulfides and sulfoxides is a more convenient and straightforward synthetic route. 

The development of new and efficient routes to chiral nonracemic sulfoxides with high enantiomeric purity has been a subject of constant interest over the last two... 

The purpose of this article is to present recent developments in the preparation of optically pure sulfoxides using both methods, mainly from 1990 to the present. Emphasis has been given to the bibliographic impact of each method. An application section is included after each route, especially in the case of variation in the Andersen methodology, where important advances have been achieved. It is not the aim of this article to review the chemistry of chiral sulfoxides—several excellent review articles have appeared on this subject, from the seminal review by Solladie19 in 1981 to other recent reviews.20 The literature has been surveyed up to January 1999. The preparation and utilization of chiral sulfoxides in asymmetric synthesis have been the subject of valuable comprehensive as well as specialized accounts which should be consulted for details and considered as complementary to this article. 

Major interest has been expressed in the synthesis of chiral sulfoxides since the early 1980s, when it was discovered that chiral sulfoxides are efficient chiral auxiliaries that are able to bring about important asymmetric transformations [22]. Sulfoxides are also constituents of important drugs (e.g., omeprazole (Losec , Priso-lec )) [23]. There is a plethora of routes of access to enantioenriched sulfoxides, and many involve metal-catalyzed asymmetric oxidations [24]. Examples of ruthenium metal-based syntheses of sulfoxides are scarce, presumably due to the tendency of sulfur atoms to bind irreversibly to a ruthenium center. Schenk et al. reported a dia-stereoselective oxidation of Lewis acidic Ru-coordinated thioethers with dimethyl-dioxirane (DMD) (Scheme 10.16) [25[. Coordination of the prochiral thioether to the metal is followed by diastereoselective oxygen transfer from DMD in high yield. The... 

Use of the chiral carbon pool for cyclopentenone preparation is also known. The fungal metabolite terrein [88] was selectively monoacetylated and then reduced with chromous chloride to enone [89]. Acetylation and olefin cleavage with ruthenium tetroxide aiwi sodium periodate led to aldehyde [90], which was readily decarbonylated to [65] (51). An alternative route (52) began with the less common S,S-tartaric acid [91], converted in four steps to diiodide [92]. Dialkylation of methyl methylthiomethyl sulfoxide with [92] gave the cyclopentane derivative [93]. Treatment of [93]... 

Hoffmann has used an isomerization of readily available aryl vinyl sulfoxides, which can be obtained in optically active form, to study the possibility of generating optically active allyl alcohols by employing chirality transfer from sulfur to carbon. While this synthetic route (Scheme 18) to allylic alcohols generally works well and gives good yields, the optical yields which could be obtained are only satisfactory in some cases, e.g. (/ )-(Z)-sulfoxide (13) gave the (S)-(+)-octenol (14) with greater than 80% optical purity, whereas the (/ )-( 5-isomer (15) yielded only 29% of the (f )-(-)-enantiomer (16 Scheme 19). 

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