Sulfur tethers

Pericas and Jeong demonstrated independently that sulfur-tethered substrates, when subjected to the PKR conditions, afforded the desired bicyclic products. The sulfur tether is removed cleanly by Pummerer reaction after oxidation of sulfur to sulfoxide or 1,4-addition of bisalkyl cuprate followed by hydrogenolysis of sulfide with Raney nickel. It is worth mentioning that the regioselectivity regarding the acetylene part is opposite to that of the intermolecular version (Equation (30)). 

With tethering technology, immobilized Rh(DiPFc) catalyst, a veiy selective hydrogenation catalyst was developed by Engelhard (26) and Chirotech (27). Rh(DiPFc)(COD)BF4 is one of most interesting homogeneous catalysts due to its chemo-selectivity and sulfur tolerant behavior. The anchored complex y-... 

Scheme 6.186) [347]. The condensation of O-allylic and O-propargylic salicylalde-hydes with a-amino esters was carried out either in the absence of a solvent or - if both components were solids - in a minimal volume of xylene. All reactions performed under microwave conditions rapidly proceeded to completion within a few minutes and typically provided higher yields compared to the corresponding thermal protocols. In the case of intramolecular alkene cycloadditions, mixtures of hexa-hydrochromeno[4,3-b]pyrrole diastereoisomers were obtained, whereas transformations involving alkyne tethers provided chromeno[4,3-b]pyrroles directly after in situ oxidation with elemental sulfur (Scheme 6.186). Independent work by Pospisil and Potacek involved very similar transformations under strictly solvent-free conditions [348]. 

The effect of the complexation is to stabilize the persulfoxide, PS. This stabilization can potentially manifest itself in a more rapid rate of formation, or alternatively, in suppression of physical quenching (kq in Fig. 25). Evidence that the latter phenomenon is of paramount importance was provided by examination of a series of sulfides with tethered olefinic linkages.96 In these cases the enhancement of reaction at the sulfur at the expense of the ene reaction at the olefinic linkages could be quantitatively predicted based upon the assumption that kq — 0. 

In the case of PEMs, the situation is more complicated because the sulfonate counter-ions (in the case of a PEM such as Nafion ) are bound to the polymer chain and are thus relatively immobile, in contrast to the free counter-ion in a small molecule acid such as sulfuric or acetic acid. Tethering of the sulfonate group can be considered to be an impediment to the mobility of the proton as it traverses the membrane. Proton mobility is also affected by the effective mean-free path of connectivity of the conduction pathway as shown in Figure 3.2. In situation (a), the increased number of dead ends and tortuosity of the aqueous domains through which proton transport occurs over the situation in (b) leads to lower overall mobility. This has been demonstrated by Kreuer and will be discussed later in this section. 

The understanding of the reactivity made possible the development of the rhodium catalyzed [4-+2+-2] carbocydization reaction as outlined in Tab. 12.9. This study demon strated that nitrogen-, sulfur-, and oxygen-tethered enynes furnish the desired cycload... 

One of the important challenges in modern synthetic and pharmaceutical chemistry is to design and develop efficient, clean, and fast routes to obtain architectural molecules from simple starting materials [102, 103]. The ewdo-selective cydoisome-rization (Scheme 4.13a) of terminal alkynes tethered to alcohols, nitrogen, and sulfur nudeophiles is one of the interesting transformations widely utilized in effident syntheses of antiviral nucleosides [104, 105], polycyclic ethers [106], and oligosac-... 

The stereochemical outcome of such cycloadditions may be altered by substituents attached to the nitrile oxide-olefin linker. Hassner and co-workers (75,240,253-255) and Kurth and co-workers (256) examined the influence of a stereogenic center a to the dipole in the cycloaddition of alkene-tethered nitrile oxides that feature a sulfur or oxygen atom within the connecting chain (Table 6.13). As expected, the diastereofacial selectivity is increased in the presence of fragments with increasing steric demand. Cycloadditions of thioethers show lower... 

This finding is rooted in the DMSO promoter and Krafft s demonstration that a suitably positioned sulfur moiety tethered to the PK precursor increases the reaction efficiency. The reaction conditions with these promoters generally require much higher reaction temperatures than that with oxidative promoters, and complete the reaction in substantially shorter periods to give high chemical yields. Moreover, the sulfur additive promotes the intermolecular PKR with even unstrained and less reactive olefins. A prominent example is the reaction between phenylacetylene and cycloheptene (Equation (3)). ... 

The intramolecular thermal [5+2] cycloaddition of 3-alkoxy-4-pyrones with sulfur- (e.g., 416) or silicon- (e.g., 419) tethered alkenes has been shown to occur with complete regio- and stereochemical control to give adducts 417 and 421, respectively. The adducts can be converted by reduction and oxidation, respectively, to the bicyclic products 418 and 421 (Scheme 69) <1993JOC5585>. It should be noted that this thermal [5+2] cycloaddition has not been realized in a bimolecular mode <1977JOC3976>. This methodology serves as an alternative to the reaction of electron-deficient alkenes with pyrone-derived 4-methoxy-3-oxidopyrylium ylides <1992TL2115>. 

Intramolecular displacement of halide ions has also been observed in several appropriately substituted complexes. For example, the thiophene unit tethered to the cyclopentadienyl ring in complex 40 can be induced to displace the chloride and form the sulfur-bound ruthenium cation 41 shown in Eq. (47) (49). 

A general problem in the synthesis of steroid compounds is the construction of a dikctone with 5/6 (raws-fused rings and a quaternary carbon atom at the ring junction. Tethering can solve this problem, and we will present two strategies—one using a lactone derived from an iodolactonization reaction, and one using a sulfur atom. 

An even more versatile tether is a sulfur atom, which can be removed completely with Raney nickel met R. neynickel in < ha r 4... 

In this second synthesis of the problematic steroid trans ring junction, the idea is to make the five-membered ring by a Claisen ester condensation and to direct the stereochemistry by tethering the cis groups with a sulfur atom. We can represent this easily in disconnection terms (Chapter 31). The cis-carbons to be joined through sulfur are shown in black. 

The expected hexacarbonyl dicobalt complex was formed when the al-kyne and dicobalt octacarbonyl were stirred in CH2C12 (73 —> 74). If the same reaction was performed in the presence of ten equivalents of NMO, the novel pentacarbonyl complex could be isolated (73->75). On dissociation of the CO ligand, accelerated by the addition of NMO, the sulfur atom is able to coordinate to the vacant site creating a stable complex. Treatment of the complex with CO resulted in regeneration of the hexacarbonyl complex and, unlike the isolated alkene-pentacarbonyldicobalt-alkyne species 68, heating of the pentacarbonyl complex 75 led to the formation of the desired cyclopentenone. A similar sulfur stabilised intermediate was isolated by Pericas and co-workers while investigating tethered chiral auxiliaries in the PK reaction.87,88... 

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