Thiolactone synthesis

Scheme 6. Photo-induced bridging of bis(thiolactones) synthesis of dithiatopazine (31), the first stable 1,2-dithietane.

The conversion of a thiolactone to a cyclic ether can also be used as a key step in the synthesis of functionalized, stereochemically complex oxacycles (see 64—>66, Scheme 13). Nucleophilic addition of the indicated higher order cuprate reagent to the C-S double bond in thiolactone 64 furnishes a tetrahedral thiolate ion which undergoes smooth conversion to didehydrooxepane 65 upon treatment with 1,4-diiodobutane and the non-nucleophilic base 1,2,2,6,6-pentamethylpiperidine (pempidine).27 Regio- and diastereoselective hydroboration of 65 then gives alcohol 66 in 89 % yield after oxidative workup. Versatile vinylstannanes can also be accessed from thiolactones.28 For example, treatment of bis(thiolactone) 67 with... 

Scheme 13. Synthesis of cyclic ethers from thiolactones.

Nucleophilic attack by an amino group on the carbonyl function of a /3-thiolactone forms the basis for a novel peptide synthesis, as illustrated by the preparation of (63) (64RCR493). Amines undergo Michael addition to the carbon-carbon double bond of thiete 1,1-dioxide (61) (62JA399). 

Only a limited number of examples are known of applications of thietanes in organic synthesis. Prominent among these examples would be electrophilic ring opening reactions leading to polyfunctional sulfur compounds (33)-(37), utilization of 3-thietanones (55) and metal complexes (87) derived therefrom as oxyallyl zwitterion equivalents in cycloaddition reactions, synthesis of dipeptide (63) with a /3-thiolactone, Raney nickel desulfurization of thietanes (e.g. 120 cf. Table 7) as a route to gem-dimethyl compounds, and desulfurization of thietanes (e.g. 17) in the synthesis of cyclopropanes (also see Table 7). 

Thiepane (35) has been synthesized by an intramolecular radical addition of the thiyl radical (equation 59) which was generated by photolysis of a thiol (71TL2025). Similarly, C—S bond formation has been achieved (equation 60) by an intramolecular condensation of 6-mercaptohexanoic acid to give the thiolactone, thiepan-2-one (135) (64MI51700). A Dieckmann-type base-catalyzed cyclization of a diester precursor followed by acid-catalyzed hydrolysis and decarboxylation has been used in the synthesis of thiepan-3-one (41) as indicated in equation (61) (52JA917). 

These methods parallel the synthesis just described for the five-membered rings. As indicated in structures (42)—(49), standard reactions of aliphatic chemistry can be extended to the preparation of piperidines, tetrahydropyrans and pentamethylene sulfides (44 Z = N, O, S) glutarimides, glutaric anhydrides and glutaric thioanhydrides (46 Z = N, O, S) and 8-lactams, 8-lactones and 8-thiolactones (49 Z = N, O, S). 

Similar absolute asymmetric synthesis was demonstrated in the solid-state photoreaction of A-(P,y-unsaturated carbonyl)thiocarbamate 41. [27] Achiral 0-methyl AT-(2.2-dmeth ibut-3-enoyl)-iV-phenylthiocarbarnate 41 crystallized in chiral space group P2i, and irradiation of these crystals gave optically active thiolactone in 10-31% ee. A plausible mechanism for the formation of 42 is rationalized on the basis that photolysis of 41 undergoes [2 + 2] cyclization to thietane and is subsequently followed by rearrangement to thiolactone 42. 

An intramolecular Heck-carbonylation/cyclization of the vinyl iodide 881 provides the 5,6-dihydropyran-2-one 882 during a total synthesis of manoalide (Equation 354) <1997CC1139>. The reaction of but-3-yn-l-ol with diaryl sulfides and carbon monoxide in the presence of a palladium(O) catalyst leads to a novel thiolactonization and hence arylthiosubstituted 5,6-dihydropyran-2-one 883 (Equation 355). Similar results are obtained with diaryl diselenides (Equation 355) <1997JOC8361>. Hydrozirconation of O-protected homopropargylic alcohols followed by carbonyla-tion and quenching with iodine provides a simple route to 5,6-dihydropyran-2-ones <1998TA949>. 

The 4,5-threo-thiobutenolide 91 thus obtained was then reduced and shortened by one carbon atom to arrive at aldehyde 92 onto which a highly stereoselective cyclopentane-forming annulation was performed via a TBSOTf/DIPEA-promoted silylative protocol. In the event, a major 2,3-cA-configured bicycle educt 94 was isolated in a 82% yield, accompanied by only 7% of fram-isomer 93. Completion of the synthesis entailed the reductive cleavage of the thiolactone bond within 93 and 94, followed by acidic deprotection, giving l-deoxy-l-thio-4a-carba-[ -D-... 

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