1,3-Oxathiane lithiation

The synthesis of the 2-acyloxathianes 3 makes use of the fact that for stereoelectronic reasons1, electrophilic attack on conformationally locked 2-lithiated oxathianes 1 leads exclusively to equatorially substituted products 2. A subsequent oxidation step completes the synthesis. 

The 1,3-oxathiane 8, derived from (5)-l,2,4-butanetriol, is lithiated to form the equatorial anion 9, which adds benzaldehyde with high induced but moderate simple diastereoselectivity (4 1) to form the alcohols 10 and 1117. The selectivity is enhanced to 7 1 by metal exchange by means of magnesium bromide. Deprotection affords (5)-2-hydroxy-l,2-diphenylethanone with 75% ee. It is expected that the method could be extended to aliphatic aldehydes. 

Oxathiane dioxides lithiated 641 synthesis of 638, 647 Oxathiane oxides, synthesis of 352 Oxathiolane oxides, synthesis of 241 Oxaziridines 72, 254, 826 as optically active oxidizing agents 291 Oxazolidinones 826 Oxazolines 619, 788... 

Eliel s oxathiane auxiliary was used for stereoselective transformations and has been reviewed in part <2003H(60)1477>. As expected, reaction of the lithiated auxiliary with acetaldehyde gave the addition product with low stereoselectivity at the side-chain stereocenter <1997M201>. Better stereocontrol was observed, when methyl Grignard reagent was added to 2-acyl-l,3-oxathiane <2000JCCS63>. Reaction of 2-vinyl-l,3-oxathiane with 1,1-diphenylethene, mediated by TiCU, afforded dihydrothiopyrans in 82% yield, albeit with low enantioselectivity (Scheme 84) <2003T1859>. 

The lithiation of 1,3-oxathiane (296) takes place with s-BuLi at —78 °C to give 2-lithio-1,3-oxathiane (315), an analogue of 2-lithio-l,3-dithiane (161), but with lower stability487. This intermediate reacts with different electrophiles, such as alkyl halides, carbonyl compounds, benzonitrile, dimethyl disulfide, dimethyl diselenide, trimethylplumbyl acetate and trimethylsilyl, germyl and stannyl chlorides488,489. However, further deprotection of 2-substituted 1,3-oxathianes has not been reported yet. 

Reactions subsequent to lithiation at C-2 of the 1,3-oxathianes derived from 5-hydroxy-1-tetralone 45 <03EJO337> and from myrtenal 46 <03JOC6619> result in the equatorial product. 

We found that PhSCH2OCH3 can be lithiated completely within 45 min at temperatures between —40 and — 45 °C using n-BuLi in THF and hexane. Subsequent functionalizations gave high yields. When during the lithiation or derivatization reaction the temperature was allowed to rise above — 20 °C, however, reduced or low yields of impure products were obtained. Since reactions with most electrophiles can be completed within 1 to 2 hours at temperatures below — 40 °C, the lower stability of PhSCH(Li)OCH3 is not a serious drawback in syntheses performed on a small or moderate scale. Problems may arise if first an alkyl chain is introduced and the methyne proton in the product PhSCH(Alkyl)OCH3 is to be replaced by lithium. 1,3-Oxathiane has been incidentally used as a substrate for lithiation-functionalization reactions [4]. 

Whereas thioanisole, CH3SPh, is reported to give a mixture of ring-metallated and side-chain-metallated products upon interaction with butyllithium, the 0,S-acetal CH3OCH2SPh is lithiated only on the methylene carbon atom by BuLi in THF or sec-BuLi-TMEDA in THF [1-3]. Analogous metallations have been realized with 1,3-oxathiane [4]. The obtained lithium compounds have a limited thermal stability [5], so functionalizations with alkyl halides and epoxides, which are usually less fast than reactions with other electrophiles , give reduced yields. The 0,S-acetal PhSCH2OCH3 can be lithiated in a reasonable time with butyllithium in a THF-hexane mixture but the temperature has to be kept below — 40 °C to prevent decomposition of the lithiated intermediate into PhSLi and other (unidentified) products [5],... 

The question of the extent to which oxygen stabilises a negative charge has been studied within the context of S-stabilised systems. Although 1,3-oxathiane (98) is deprotonated at C-2, a mode of reactivity that has been impressively exploited by Eliel, the corresponding sulphone (99) undergoes lithiation exclusively at C-4 ... 

The j -BuLi-(—)-sparteine combination is widely used in enan-tioinductive organic reactions. 4.H7-i22 Benzylic asymmetric alkylation may thus be achieved by subsequent treatment with alkyl halides, alkyl tosylates, and allyl tosylates 1,3-Oxathiane derivatives shown in eq 50 may be lithiated and quenched with electrophiles. An interesting aspect of this reaction is the equatorial stereoselectivity, which is independent of the size of the electrophile introduced. ... 

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