Pyridyl sulfoxides

Demailly and coworkers195 found that the asymmetric induction increased markedly when optically active methyl pyridyl sulfoxide was treated with an aldehyde. They also synthesized (S)-chroman-2-carboxylaldehyde 152, which is the cyclic ring part of a-tocopherol, by aldol-type condensation of the optically active lithium salt of a,/3-unsaturated sulfoxide. Although the diastereomeric ratio of allylic alcohol 151 formed from lithium salt 149 and 150 was not determined, the reaction of 149 with salicylaldehyde gave the diastereomeric alcohol in a ratio of 28 72196. 

Coupling Reactions of Pyridyl Sulfoxide with PhMgBr... 

In the reactions of 2-pyridyl sulfoxides with Grignard reagents (71CC649), benzylic groups tended to couple preferentially with the p-... 

Heterocyclic amines have also been used as phase transfer catalysts. However, because these amines quaternize easily, the question is whether the operative catalyst is the tertiary amine or the quaternary ammonium salt formed in situ Furukawa et al.286 have shown that a methyl 2-pyridyl sulfoxide may be used as a phase transfer catalyst and promote substitution reactions between lithium chloride or sodium cyanide and benzyl bromide. According to the authors, the catalyst behaves as a cation complexer and not as a quaternary ammonium salt formed in situ by a Menschutkin reaction. 

The adducts resulting from Diels-Alder reaction of pyridyl sulfoxides with furan have been used in the synthesis of a number of natural products. Thus, a new procedure for the total synthesis of optically actives C-nucleosides was reported by Koizumi et al. [38], who prepared D-showdomycin (19) and (D)-3,4-0-isopropylidene-2,5-anhidroallose (20) from the endo(t) 18a adduct (Scheme 10). (-i-)-Methyl 5-epishikimate (21) [39] and pentaacetyl- -D-mannopyranose (22) [40] were also obtained starting from endo(t) 18a (Scheme 10), the cleavage of the oxygenated bridge being the key step of these transformations. 

The introduction of an electron-withdrawing group (N02 or CF3) at the pyridine ring of 2-pyridyl sulfoxides enhances the dienophilic reactivity. The results obtained from racemic dienophiles ( )-14, ( )-25, and ( )-26 with furan are shown in Scheme 12 [41]. The reactions took place with moderate endo/exo selectivity in all cases but the 7r-facial selectivity was quite high (for both endo and exo approaches) when substituted pyridines 25 and 26 were used as dienophiles. 

Suitable cryptands have been used to increase greatly the rates of reactions where F , Br , P, OAc, and CN are nucleophiles." Certain compounds that are not cryptands can act in a similar manner. One example is the podand tris(3,6-dioxaheptyl)amine (103), also called TDA-1." Another, not related to the crown ethers, is the pyridyl sulfoxide 104." " ... 

Tandem condensation of chiral a-alkoxy aldehydes with the anion of allyl 2-pyridyl sulfoxide and (MeO)3P-promoted desulfurization of the resulting a-adduct provide ( )-alkoxydiols. llie major stereochemical path in their preparation may be accounted for by the Felkin- ih (nonchelation control) model (Scheme 19). ... 

Another synthetic strategy that produces substituted bipyridines in moderate to high yields involves coupling of pyridyl sulfoxides with pyridyl Grignard reagents (Scheme 3).44,45... 

In the case of the reaction of the benzyl (4-pyridyl)sulfoxide (53) with phenylmagnesium bromide, a similar reaction of ligand coupling took place easily to lead to 4-benzylpyridine (54)72... 

Better yields of the ligand coupling product were obtained when the reaction was performed on the more sterically hindered 4-(3-substituted pyridyl)sulfoxide derivatives (146) or (147)91... 

In contrast to 2-pyridyl sulfoxide, both 3- and 4-pyridyl p-tolyl (or phenyl) sulfoxides were found exclusively to undergo the ligand-exchange reactions to eliminate stereospecifically 3- and 4-pyridyl Grignard reagents and phenyl p-tolyl sulfoxide. The optical activity of phenyl p-tolyl sulfoxide indicated that the stereochemistry had been completely inverted. The resulting 3- and 4-PyMgBr... 

Table 4. Ligand coupling and exchange reactions of phenyl pyridyl sulfoxides with PhMgBr ...

As an extension to the ligand-coupling reactions, cross-coupling reactions using various phenyl pyridyl sulfoxides with pyridyl Grignard reagents were carried out, and the results are shown in Scheme 22 and Table 5 [58]. 

The various cross-coupled biheteroaryls thus obtained are shown in Table 4. These results suggest that the reactivity of pyridyl sulfoxides and PyMgBr is in the following order, namely, 2-Py>4-Py 3-Py. This cross-coupling reaction is a convenient procedure for providing numerous unsymmetrical biheteroarylic compounds. 

Table 5. Cross-coupling reactions of pyridyl grignard reactions and pyridyl sulfoxides ...

In the absence of groups with high migratory aptitude, the reaction takes another course. Simple alkyl 2-pyridyl sulfoxides react with phenyl-... 

The enantioselective reduction of acylpyridines has been improved by the addition of trimethoxyborane to the oxazaborolidine reagent <97SL273, 97T12405>. An alkyl pyridyl sulfoxide is resolved by complexation with a chiral host compound derived from tartaric acid <97TA2505>. 

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