Arylalkyl-thioethers

In 2002, Venkataraman published the synthesis of bisaryl- and arylalkyl-thioethers catalyzed by the Cul/neocuproine system [74]. At the same time, using excess ethylene glycol as a ligand, Cul-catalyzed coupUng of aryl iodides with thiols was found to take place at 80 °C [75]. Soon after, N,N-dimethylglycine (L2) (Table 9.15, entry 1) [76] and L-proline (LI) (entry 2) [77] were revealed to be effective for the same transformation. Recently, CuBr/ 3-keto ester (L19) was reported to be able to promote this cross-coupling reaction to afford the corresponding diaryl thioethers at 60-75 °C (entry 3) [27]. 

Metabolites derived by loss of an alkyl or arylalkyl group from ethers [Eq. (4)], thioethers [Eq. (5)], amines [Eq. (6)], and amides [Eq. (7)] represent common biotransformation pathways (R, R" = H, alkyl or aryl). These processes involve oxidation on carbon adjacent to the heteroatom. The intermediates are generally unstable and readily decompose to the corresponding alcohol, thiol, amine, or amide and an aldehyde. Intermediates formed from amides [Eq. (7)] are more stable and may be detected as excreted metabolites. If a secondary carbon atom is adjacent to the heteroatom, then this portion of the molecule is released as a ketone. The heteroatom may also be located in a cyclic structure (e.g., morpholine, piperazine). Two processes have been adopted for amines, namely, N-dealkylation or deamination, that are essentially the same event. In general, which of the two terms applies depends on the... 

This reagent reacts more rapidly with primary than with secondary alcohols. This property has been made use of to transform the primary hydroxy groups of sugars to salts, which then may be converted to halides (Cl, Br, I), azides, amines, thiols, thiocyanates, etc. by reaction with appropriate nucleophiles (eq 10). Arylalkyl ethers and thioethers may also be prepared by appropriate modification of this method. These reactions generally proceed with high stereoselectivity. Thus reaction of chiral 2-octanol with this reagent afforded 2-chlorooctane with complete inversion... 

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