Grignard reagents with sulphoxides

TABLE 8. Formation of sulphoxides, R2S=0, from the reaction of Grignard reagents with sulphurous acid derivatives, SOX2... 

Few racemic alkyl p-tolyl sulphoxides were prepared in rather low yields (16—40%) by the reaction of Grignard reagents with mixed anhydrides 108, 109 and compound HO formed in situ from p-toluenesulphinic acid and 3-phthalimidoxy-l,2-benzoisothiazole 1, 1-dioxide167 (equation 59). The mixed anhydrides 109 or 110 when reacted with cyclopen-tene and cyclohexene enamines 111 gave the corresponding a-ketocycloalkyl sulphoxides 112 in low yields (10-41%) along with small amounts of several by-products such as disulphides and thiosulphonates167 (equation 60). 

Strecker153 was also the First to show that diethyl sulphite reacts with two equivalents of Grignard reagent in ether solution to yield symmetrical sulphoxides (equation 50). Bert156... 

Treatment of (—)-(S)-276 with allyl Grignard reagents gives optically active allylic sulphoxides 288. This reaction, however, involves an allylic rearrangement via transition state 289 as evidenced by Mislow and his collaborators362 (equation 160). 

A closely related reaction of (—)-(S)-276 with the Grignard reagents obtained from a-acetylenic halides leads to the formation of mixtures of acetylenic sulphoxides 290 and allenic sulphoxides 291363 (equation 161). The latter compounds are most probably formed via transition state 292, which is analogous to 289. On the other hand, hex-l-ynyl p-tolyl sulphoxide 293 is smoothly prepared from hex-1 -ynylmagnesium bromide and (— )-(S)-276363 (equation 162). 

Gaoni has published197 a novel preparation of 1,3- and 1,4-dienylic sulphoxides in which certain sulpholenes or sulpholanes can be cleaved with two equivalents of a Grignard reagent. The reactions outlined in equation (86) can be classified formally as a double reduction at the sulphur atom. The 1,4-dienylic sulphoxides can be obtained by the same type of reactions, via bicyclo[3.1.0] sulphones, that are accessible from the sulpholenes and dichlorocarbene, followed by dechlorination with LiAlH4197. Yields for all the reactions are poor to modest (26 to 66%). 

Nitrosolysis of camphor ethyl acetal with ethanolic ethyl nitrite in sulphur dioxide yields the orthoester oxime (205) which is rapidly dehydrated by excess acetal to the orthoester nitrile which then reacts with sulphur dioxide to form the ester nitrile and diethyl sulphite.Further papers in this section include the full paper on ozonolysis of silyl ethers (Vol. 5, p. 33), another synthesis of camphor-enol trimethylsilyl ether (cf. Vol. 6, p. 41)/°° the conversion of camphor oxime with Grignard reagents into the corresponding imine with no aziridine formation/° the preparation of (206) by treating bornylene with trichloroacetyl isocyanate/ the oxidation of thiocam-phor to the 5-oxide and alkylation in the presence of thallium(i) ethoxide to a/S-unsaturated sulphoxides/ and the free-radical C-3 alkylation of camphor with alkenes. " ... 

The synthesis of the 3- and 4- pyridyl Grignard reagents (120) and (121) has been achieved by reaction of the corresponding phenyl pyridyl sulphoxide with phenyl magnesium bromide (Scheme 34). The pyridyl Grignards were trapped with aldehydes and ketones, and the... 

Grignard reagents behave similarly,and a thioborane gives an un-symmetrical sulphide with a sulphenate ester. Tris(diethylamino)-phosphine converts cystine derivatives into corresponding lanthionines [NH2 CH(C02H) CH2]2S, 2 and the disulphide formed between penicillin sulphoxide and Bu SH (36 fine s in place of Me at S) forms the ethyl sulphide (36 Et in place of Me at S) by treatment with triethylphosphine. ... 

Keto esters.—Acylimidazolides react readily with Grignard reagents to provide a general method for the synthesis of a-keto-esters yields are variable over a series of 11 examples. /3-hydroxy-esters and ketones, obtained by the aldol condensation, have been oxidized to /3-keto-esters and ketones most efficiently by the Swern procedure using dimethyl sulphoxide and oxalyl chloride. Sulphide contraction of thiopyrrolidines has been shown to be an effective synthesis of /3-keto-esters and nitriles (Scheme 42). ... 

Thietan 1-oxide has been found to react with Grignard reagents to give 2-substituted thiolans in fair yield. This unusual transformation appears to involve reduction of the sulphoxide function to a sulphide, with concomitant a-substitution, followed by a Lewis-acid-catalysed ring-enlargement reaction. 

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