Lithiated dithioacetals

Acyl-lithiums and their Equivalents. Details have appeared of the preparation of di-isopropylcarbamoyl-lithium (LiCONPr a) by reaction of di-isopropylformamide with t-butyl-lithium. Lithiated dithioacetals, particularly those derived from dithians, continue to be popular. Alkylations of such species have been important reactions in syntheses of 25-hydroxycholesterol, pyrenophorin and vermiculin," and several chain-elongated sugars. 2-(3,3-Dialkoxypropyl)-l,3-dithians may be converted via their lithiated derivatives into protected 2-hydroxycycIobutanone derivatives (Scheme 1), themselves potential synthons for 1,4-diketones and cyclopentenones. ... 

Mukaiyama reported the conjugate addition of a-dithioalkylcuprates to 2-enones (73-94% yields) for the synthesis of 1,4-diketones, and the reaction was exploited in a synthesis of(+)-dihydrojasmone [141]. Few reports on a-thioalkylcuprates have appeared since then. Cuprates formed from lithiated ketene dithioacetals and... 

The most popular method for generation of a-thio-carbanion (migration terminus) is direct lithiation (deprotonation) with alkyllithium or lithium amide. These deprotonation methods are widely applicable to various substrates, not only benzyl or allyl sulfides , but also dithioacetals 142 which form 143 (equation 83), and a phosphonate substituted system 144 which gives 145 (equation 84). ... 

Dithioacetals (see also dithianes and dithiolanes) alkylation of 98 as acyl anion equivalents 75 carbanions of 87,97-102 cleavage of 14-18,98,102 desulfurization of 78 metal-catalysed coupling 127 reaction with Grignard reagents 127 reductive lithiation of 89 synthesis of 12-19,97-102 Dithioacids synthesis of 40... 

Oxidation of a thioacetal at one of the sulfur atoms offers some useful features. After formation of the carbaniun and addition to an electrophilic partner, the hydrolysis is easier than for dithioacetals and can be made with dilute sulfuric or perchloric acid. Moreover, the addition of a lithiated carbanion derived from these species to enones occurs in a 1,4 rather than a 1,2 manner (the usual way for less stabilized more reactive thiocarbanions). The chemistry of these thioacetal monoxides was developed in the 1970s mainly by Ogura and Tsuchihashi [287-290] and by Schlessinger and co-workers [291-293], Two examples of application are given. 

The use of reductive lithiation to prepare a carbanion from a dithioacetal is due to Cohen [311] ... 

The simple reductive lithiation and quench of dithioacetals means that a-functionalised - and in particular, a-silylated sulfides are very easy to prepare. Cohen has exploited this in a number of ways for example, a ketenedithioacetal 70 can be used to generate an a-lithiovinylsilane 71 if a silyl halide is used as the electrophile in the first step.85... 

Lithiosilanes derived from cyclopropane dithiocetals add to aldehydes to give precursors for Peterson olefinations - one of the best ways of making alkylidene cyclopropanes. In the example below, the lithiated allyl sulfide 72 adds cleanly to a ketene dithioacetal to give cyclopropane 73. Successive reductive lithiations give silane 74 and then a mixture of... 

Methyl glyoxylate dithioacetal 292, after lithiation, reacted with a protected D-mannitol triflate in the presence of HMPA. This methodology has been applied to the synthesis of 3-deoxy-D-manno-2-octulosonic acid (KDO)462. A related ethyl glyoxylate dithioacetal 293 gave conjugate addition to different Michael acceptors, such as a,fi-unsaturated esters, lactones and lactams463,464. 

The high diastereoselectivity attending the spirocyclisation of ketene dithioacetals provides an effective means for controlling the stereochemistry of a methyl substituent at the a-position on a 6-lactone ring,244 The method was applied to the synthesis of the polyether antibiotic Salinomycin [Scheme 2.120].242 Condensation of the methyl ketone 120 1 with the lithiated l,3-dithian-2-yl-phospho-nic acid diethyl ester 120.2 gave the ketene dithioacetal 1203 in 76% yield. After hydrolysis of the two benzoate ester groups, cyclisation of diol 120.4 was... 

A highly useful twofold reaction of silyl dithioacetals with epoxides was described by Tietze and coworkers (Scheme 2.107) [249]. Treatment of 2.2equiv. of enan-tiopure epoxides 2-463 with lithiated silyldithiane 2-458b in the presence of a crown ether led to 2-467 after aqueous work-up. It can be assumed that by attack of the lithium compound 2-462 at the sterically less-hindered side of the epoxide 2-463, the alkoxide 2-464 is formed which in a subsequent Brook rearrangement produces the lithium dithioacetal 2-465. This reacts again with an epoxide to give 2-466 and furthermore 2-467. Treatment with NaF then leads to the diol 2-468 which can be converted into the dihydroxy ketones 2-469 and the corresponding 1,3,5-triols, respectively. 

The dithiane-derived anion can be generated by the action of Bu°U in THF at -78 C or with complex bases NaNH2-RONa at room temperature. Lithiated dithiane can also be prepared in situ by sonica-tion of n-butyl chloride with lithium in the presence of dithiane. Dithioacetals or ketals are resistant to acidic or basic hydrolysis. Regeneration of the carbonyl group from the dithioketal sometimes presents difficulties but can be carried out by hydrolysis in polar solvents (acetone, alcohols, acetonitrile) in the presence of metallic ions such as Hg , Cu, Ag, 71 177 qj j m ise Alternatively, alkylative hy lysis... 

Among various strategies towards ulosonic acids various acylation reactions are often used. They involve alditol derivatives as convenient substrates, and diverse acyl anion equivalents. Here belongs the synthesis of KDO, developed by Shiba et al. [84], By reaction of the triflate 67 with the lithiated 68, eight carbon atoms compound 69 was obtained (Scheme 17). Removal of O-acetyl residue with subsequent NBS promoted oxidative hydrolysis of the dithioacetal moiety resulted in the formation of KDO derivative 70. 

More recently, a strategy based on the reaction of l,2-anhydro-3,4 5,6-di-O-isopropylidene-D-mannitol (74) with the lithiated silyl dithioacetal has been reported [87]. As a result, the alcohol 75 was formed which under acylation with methyl chloroformate furnished carbonate 76 (Scheme 19), converted further to the lactone 77. Direct transformation of dithioacetal 77 into the corresponding ketone failed, despite the different methods used [88]. It succeeded in two steps procedure, involving its conversion into dimethylketal, followed by hydrolysis [89], to afford 78, being the known precursor of KDO [90]. 

The displacement of primary iodides in some carbohydrate derivatives by lithiated 2-trimethylsilyl-l,3-dithiane followed by hydrolysis of the dithioacetal has allowed the synthesis of some acylsilanes (e.g. 21 from 20), and a review on the oxidation of the carbon-silicon bond has included a number of carbohydrate examples. ... 

Monosaccharides. - 1.1.1 Acyclic Compounds. A new route to 2-deoxypentose dialkyl dithioacetals 2 involved opening of the L-ascorbic add-derived epoxide 1 with lithiated formaldehyde dialkyl dithioacetals. Standard protecting group manipulations converted 2 (R = Bu ) to the 4-mesylate 3. ... 

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