Cyclic thioethers, synthesis

Although sodium sulphide reacts readily with haloalkanes [2] and activated aryl halides (see Chapter 2) [e.g. 3-5] in the presence of a quaternary ammonium catalyst to form symmetrical thioethers (Table 4.1), a major side reaction results in the formation of disulphides owing to the oxidation of the intermediate thiols under the basic conditions. Consequently, little use has been made of this procedure for the synthesis of thioethers [3, 6], but the corresponding reaction of the a,(0-dihaloalkanes to yield cyclic thioethers has proved to be a valuable procedure for the synthesis of thietanes [7] (Table 4.2). The ring closure with the secondary dihaloalkanes is considerably more difficult to effect than is the reaction of the primary dihaloalkanes. 1,3-Dihydrobenzo[c]thiophene (89%) is produced in the reaction of 1,2-bis(bromomethyl)benzene with sodium sulphide (Scheme 4.1) [8]. The direct... 

A superior and relatively versatile procedure for the synthesis of unsymmetrical dialkyl thioethers, which avoids the unattractive direct use of thiols, utilizes the stable l-alkylthioethaniminium halides, which are readily obtained from thioacet-amidc [32] (Scheme 4.4). The reaction has also been used for the synthesis of alkyl aryl thioethers from activated aryl halides [33], but it cannot be used for the synthesis of cyclic thioethers, as polymeric sulphides are formed from a,co-dihaloalkanes. A similar sequence to that which leads to the thioethers has been used for the synthesis of S-alkyl thioesters [34] (see 4.1.26). 

Shift of sulfonium ylide has been applied in organic synthesis as a useful methodology for carbene insertion into a G-S bond. This reaction has been particularly applied in the synthesis of cyclic thioethers, as shown in Equation (19)." " ... 

This reaction is representative of the synthesis of cyclic thioethers from acyclic dithiols mediated by caesium carbonate in DMF. 

An example in which a portion of the cysteine carbon chain is incorporated directly is one of the proposed routes for biotin synthesis by microorganisms. An acyl coenzyme A derivative of pimelic acid condenses with cysteine, eliminating COg. Reaction with carbamyl phosphate leads to the formation of an ureido ring system. The thiol then forms a cyclic thioether by addition to a double bond resulting from dehydration. 

In this synthesis, our procedure for the preparation of 1,5,9-trithiacyclodode-cane 12S3 from the strained cyclic thioether known as thietane (SCH2CH2CH2) is described [see Eqs. (1) and (2)]. 

In this synthesis, a convenient procedure for the preparation of heptacarbonyl-disulfidodimanganese, Mn2(CO)7( i-S2), from the acetonitrile derivative of Mn2(CO)io and the strained cyclic thioether known as thiirane (SCH2CH2), which serves as a source of sulfur, is described. 

Conversion of Thioketones to Ketones. Thioketones generated by a Norrish-type photofragmentation of a sulfenyl acetophenone are trapped in situ by [3 + 2] dipolar cycloaddition with a silyl nitronate (eq 10). Fluoride treatment of the resulting heterocycle produces the ketone. This transformation is compatible with a variety of functional groups and has been used as part of a synthetic manipulation in which an a-acyl cyclic thioether is converted stereoselectively, with ring enlargement, to a ketolactone (methynolide synthesis). ... 

A wide variety of /3-lactams are available by these routes because of the range of substituents possible in either the ketene or its equivalent substituted acetic acid derivative. Considerable diversity in imine structure is also possible. In addition to simple Schiff bases, imino esters and thioethers, amidines, cyclic imines and conjugated imines such as cinnamy-lidineaniline have found wide application in the synthesis of functionalized /3-lactams. A-Acylhydrazones can be used, but phenylhydrazones and O-alkyloximes do not give /3-lactams. These /3-lactam forming reactions give both cis and /raMS-azetidin-2-ones some control over stereochemistry can, however, be exercised by choice of reactants and conditions. 

Cyclizations of alkenic amines and imines using organoiron complexes to generate bicyclic 3-lactams are discussed in Chapter 3.1 of this volume. Examples of heterocyclizations of alkenic NA/-dialkylamine and pyridine derivatives to form cyclic quaternary ammonium salts are cited in the Staninets review.Ic A cyclization of an enol thioether has been used to generate a thiazolidine intermediate used in cephalosporin synthesis (equation 131).262... 

This methodology was extended to the synthesis of various sulfur heterocycles. Thiols and thioacetates can participate in such reactions giving cyclic (phenylseleno)thioethers. Selected examples are shown25b. 

Trost, B. M., Vaultier, M., Santiago, M. L. Thionium ions as carbonyl substitutes. Synthesis of cyclic imino thioethers and lactams. J. Am. Chem. Soc. 1980,102, 7929-7932. 

A one-pot variation of the thioether generation, applicable to the formation of cyclic sulfones, involves reaction of a dihalide (or halide equivalent) with a divalent sulfide, such as sodium sulfide. This methodology was used in the synthesis of conduritols, whereby sodium sulfide reacted with diepoxy stereoisomers 13 in a one-step thioether formation fScheme 8.5). The resulting thiapane isomers 14 were separated (HPLC) and then individually methylated and oxidized with m-CPBA to a set of isomeric sulfones, 15. 

Alternatively, for the synthesis of cyclic products, the thioether or sulfone can act as a tether, enabling an alternative reaction to serve as a cyclization step (Scheme 8.17bl. If this intramolecular reaction is not orthogonal to alkene reactivity, such separation of the RBR from its predecessor steps is essential. This strategic advantage of the RBR has been underutilized in synthesis. 

Thioethers. A mixture of diphenyl sulfoxide and HMPA treated with SmL in THF under N2 at 20 for 1 min, diluted with hexane, and filtered through Florisil - diphenyl sulfide. Y 94%. The method can also be used for the rapid deoxygenation of sulfones (which may be viewed as protected thioethers). E Diphenyl sulfone under the same conditions - diphenyl sulfide. Y 93%. Esters remained intact and, in some cases, sulfoxides were selectively reduced in the presence of ketones. F.e. inch formation of cyclic tert. amines from N-oxides, tert. phosphines from phosphine oxides, and distannanes from distannoxanes, s. Y. Handa et al., J. Chem. Soc. Chem. Commun. 1989, 298-9 review of synthesis and use of polysulfoxides s. V.A. Nikonov, G.V. Leplyanin, Sulfur Reports 9, 1-23 (1989). 

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