Sulfur-centered Nucleophiles

One of the earliest useful methods for asymmetric opening of meso-epoxides with sulfur-centered nucleophiles was reported by Yamashita and Mukaiyama, who employed a heterogeneous zinc tartrate catalyst (Scheme 7.10) [20]. Epoxides other than cydohexene oxide were not investigated, and the enantioselectivity depended strongly on the identity of the thiol. 

Without question, the most significant advance in the use of sulfur-centered nucleophiles was made by Shibasaki, who discovered that 10 mol% of a novel gallium-lithium-bis(binaphthoxide) complex 5 could catalyze the addition of tert-butylthiol to various cyclic and acyclic meso-epoxides with excellent enantioselectiv-ities and in good yields (Scheme 7.11) [21], This work builds on Shibasaki s broader studies of heterobimetallic complexes, in which dual activation of both the electrophile and the nucleophile is invoked [22]. This method has been applied to an efficient asymmetric synthesis of the prostaglandin core through an oxidation/ elimination sequence (Scheme 7.12). 

Jacobsen demonstrated that the (salen)Cr system used to effect intermolecular, cooperative asymmetric azidolysis of meso-epoxides (Schemes 7.3 and 7.5) could be applied to sulfur-centered nucleophiles (Scheme 7.13). In order to overcome moderate enantioselectivity (<60% ee), a dithiol nucleophile was employed as part of a double resolution strategy in which the minor enantiomer of the monoaddition product reacts preferentially to form the meso- bis-addition product, thereby increasing the ee of the C2-symmetric bis-addition product. Enantiopure 1,2-mer-capto alcohols (>99% ee) were obtained from the meso-epoxide in ca. 50% overall yield by a burdensome (though effective) multistep sequence, [23]. 

Stereoselective Michael additions of carbon-, nitrogen-, oxygen-, and sulfur-centered nucleophiles to 6,7-dehydro-5-oxoindolizidine have been reported <2006JOC6630>. 

The reactivity of sulfur-centered nucleophiles such as thiourea anion [46] and thioacetate anion [17] in photoinduced SRN1 reaction has been reported as a one-pot, two-step method for the synthesis of several sulfur-aromatic compounds from moderate to good yields. Without isolation, the ArS ions obtained by the aromatic substitution are quenched with Mel to yield ArSMe in a one-pot procedure, together with Ar2S in variable yields, from an SRN1 between ArS- and aryl radicals (Scheme 10.3). 

Schmidt, L.C., Argiiello, J.E. and Penenory, A.B. (2007) Nature of the chain propagation in the photostimulated reaction of 1-bromonaphthalene with sulfur centered nucleophiles. Journal of Organic Chemistry, 72, 2936-2944. 

Kieltsch, I., Eisenberger, P. and Togni, A. (2007) Mild electrophilic trifluoromethylation of carbon- and sulfur-centered nucleophiles by a hypervalent iodine(III)-CF3 reagent. Angew. Chem. Int. Ed., 46, 754-757. 

A one-pot oxidative conjugate addition of sulfur-centered nucleophiles to MBH adducts has been developed by Yadav et The reaction involves... 

In 1982, a new reaction was reported by Tamura and Ono namely, allylic nitro compounds undergo replacement of the nitro group by various nucleophiles in the presence of a palladium (0) catalyst.17a b 18a b The details of these reactions are discussed in Ref. 2b here, only some typical examples are presented. Carbon, sulfur, nitrogen, and phosphorous centered nucleophiles replace the nitro groups at the allylic positions. The reaction of allylic nitro compounds with triphenylphosphine is applied to the highly stereoselective olefination of aldehydes (Eqs. 7.15-7.18).19... 

This section surveys the most important reactions of chiral organo-sulfur compounds. Some of these were touched on in the previous sections. For the sake of convenience, a variety of reactions occurring at the chiral sulfur center are divided into three main types of reactions racemization, nucleophilic substitution reactions, and electrophilic reactions. 

Perfluorotetramethylene sulflmides are synthesized by the reaction of lithium amide and pnmary amines with (perfluorotetramethylene)sulfur difluonde [7(5] (equation 13) (Table 6) The products can be oxidized with m-chloroperoxybenzoic acid to the corresponding sulfoximides (equation 13) or can be treated with chlorine or bromine to yield N-halo derivatives [76] The reaction of CF3SF3=NCF3 with nucleophiles takes place by attack of the nucleophile at the positive sulfur center [17] (equation 14)... 

One of the most useful and widely used applications in the synthesis of natural product derivatives relies on the efficient photoaddition of RS-H onto a double bond (a reaction known as thiol-ene coupling) [55], The reaction exploits the weakness of the S—H bond that can be cleaved homolytically under irradiation (atca. 254nm). The electrophilic sulfur-centered radical attacks a nucleophilic double bond, thus starting a radical chain reaction. 

Moreover, N-sulfinyl oxazolidinones have been shown to be good intermediates for the synthesis of chiral sulfinate esters and sulfinamides with excellent ee. In all cases, the absolute configuration of the sulfoxide obtained is in agreement with the fact that nucleophilic displacement occurs with inversion of configuration at the sulfur center in the starting /V-sulfinyl oxazolidinone. 

Some intramolecular additions to thiopyrylium ions involving sulfur as nucleophilic center have been reported in Sections IV,B,1 and 2. 

C-Sn [148] and C-Si [121, 149] bond cleavage has developed into a versatile synthetic method for adding functionality a to nitrogen, oxygen and sulfur centers. C-Si bond cleavage is known to be induced by nucleophiles such as pyridine [150] and methanol, and stereoselectivities have been interpreted as indicating that C-Si bonds can even be attacked by a double bond system [151]. 

A sulfur center in oligomeric or polymeric elemental sulfur as well as in sulfur compounds (especially those with catenated sulfur chains) can be attacked by electrophiles and nucleophiles. By far the most important electrophilic attack is the reaction of sulfur with oxygen (also the oxidation of sulfur compounds with oxidation states below -1-6, e.g., H2S or SO2). Despite the complicated and not fully understood mechanism as well as the economic importance (formation of H2SO4), those reactions of sulfur with oxygen are beyond the scope of this section. 

There are several efficient methods available for the synthesis of homochiral sulfoxides [3], such as asymmetric oxidation, optical resolution (chemical or bio-catalytic) and nucleophilic substitution on chiral sulfinates (the Andersen synthesis). The asymmetric oxidation process, in particular, has received much attention recently. The first practical example of asymmetric oxidation based on a modified Sharpless epoxidation reagent was first reported by Kagan [4] and Modena [5] independently. With further improvement on the oxidant and the chiral ligand, chiral sulfoxides of >95% ee can be routinely prepared by these asymmetric oxidation methods. Nonetheless, of these methods, the Andersen synthesis [6] is still one of the most widely used and reliable synthetic route to homochiral sulfoxides. Clean inversion takes place at the stereogenic sulfur center of the sulfinate in the Andersen synthesis. Therefore, the key advantage of the Andersen approach is that the absolute configuration of the resulting sulfoxide is well defined provided the absolute stereochemistry of the sulfinate is known. 

---