Corey-Seebach procedure

In an extension of the procedure, thiols react with gem-dihaloalkanes (Table 4.4) to produce thioacetals [ 10,20-23] and the reaction can be employed in the Corey-Seebach synthesis of aldehydes and ketones (see ref. 24 and references cited therein), gem-Dichlorocyclopiopanes having an electron-withdrawing group at the 2-position react with thiols to produce the thioacetals [25]. In the corresponding reaction of the thiols with biomochloromethane exclusive nucleophilic substitution of the bromo group by the thiolate anion occurs to yield the chloromethyl thioethers [13, 14] (Table 4.5). 

This method for the preparation of cyclobutanone via oxaspiropentane is an adaptation of that described by Salaiin and Conia. The previously known large-scale preparations of cyclobutanone consist of the reaction of the hazardous diazomethane with ketene, the oxidative degradation or the ozonization in presence of pjrridine of methylenecyclobutane prepared from pentaerythritol, or the recently reported dithiane method of Corey and Seebach, which has the disadvantage of producing an aqueous solution of the highly water-soluble cyclobutanone. A procedure involving the solvolytic cyclization of 3-butyn-l-yl trifluoro-methanesulfonate is described in Org. Syn., 54, 84 (1974). 

We owe to Corey and Seebach [302] an efficient procedure for the generation of phenylthiomethyllithium (PhSCH2Li), opening the way for practical applications. They found that this reagent was produced in about a 97% yield through reaction of equimolar amounts of n-butyllithium, DABCO and thioanisole in THF at 0°C for 45 min. 

The following experimental procedures illustrate the use of these Teagents for the synthesis of the monosulfoxide (2) and monosulfone (3) derived from the useful 1,3-dithiane (1) of Corey and Seebach (they can and have been used in a similar fashion). 

Dithioacetals are important synthons in organic synthesis as acyl-masked reactants. The synthesis carried out by Corey and Seebach [69] is a two-step procedure alkylation with a reactive iodo electrophile followed by monomethyla-tion of disulfide [Eq. (36)]. 

As an example, the methyl group in thioanisole can be metalated using n-butyllithium to produce phenylthiomethyllithium by contrast, anisole under the same conditions is metalated at an ortho position. This reaction has been of little practical use in synthesis since the maximum yield of the lithium intermediate is only about 35%. However, Corey and Seebach (23) recently developed an excellent procedure for generating phenylthiomethyllithium in essentially quantitative yield by reaction between equimolar amounts of thioanisole, n-butyllithium, and DABCO in tetrahydrofuran at 0°C. 

Seebach D, Corey EJ (1975) J Org Chem 40 231. A general procedure for the alkylation of 2-lithiated 1,3-dithianes is given. In our opinion the reaction times mentioned in this paper can be shortened considerably compare Seebach D, Beck AK (1971) Org Syntheses 51 76... 

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