Ketones, preparation using 1,3-dithiane

Ketone, aralkyl, selective a-bromina-tion of,53, 111 Ketone, heptyl phenyl, 53,78 Ketones, preparation using 1,3-dithiane, 50,74 51,80... 

The intramolecular carbonyl addition of a lithiated dithiane to a ketone was used in the synthesis of ro-caglamide, an anticancer compound, in 64% yield. a-Hydroxy ketcxies having fungicidal activity were prepared from die reaction of lidiiated 2-alkyldi-thianes with 3-pyridyl ketones. ... 

RSSiMe3 [R = Me, Et, (-CH2-)3], Zn, Et20, 0-25°, 70-95% yield. This method is satisfactory for a variety of aldehydes and ketones and is also suitable for the preparation of 1,3-dithianes. Methacrolein gives the product of Michael addition rather than the thioacetal. The less hindered of two ketones is readily protected using this methodology. ... 

Thioacetals and thioketals have significant synthetic potential for use in organic chemistry but are often neglected because of their unpleasant odor. A polymeric reagent for the preparation of ketones via 1,3-dithianes has been reported using... 

The lithiation of y-chloro acetal 175 with lithium and a catalytic amount of naphthalene (4%) allowed the preparation of the intermediate 176, which can be considered as a masked lithium homoenolate, and was used for the preparation of the hydroxy ketone 179 through the hydroxy acetal 177 and dithiane 178 using known chemistry (Scheme 62)" . 

One hydrolytic method that is useful for the preparation of ketones is the hydrolysis of dithianes. 1.3-Dithiane can be alkylated by treatment with butyl lithium followed by an alkylating agent. The two sulfurs flanking the acetal carbon acidify the protons on that carbon such that butyl lithium can remove one giving a sulfur-stabilized anion. This anion reacts with alkyl halides or sulfonates to give alkylated products. This sequence can be repeated to give a bis-alkylated product. Hydrolysis then yields a ketone. Ditliioacetals are much more resistant to hydrolysis than acetals and thus Hg2+ is often used to promote efficient hydrolysis. 

Some of the problems associated with the synthesis of a-dicarbonyl starting materials have been alleviated by the use of propane-1,3-dithiol, which reacts with aldehydes to give cyclic thioacetals. With butyllithium the resulting stable dithiane anions (134) can be transformed into a-diketones or a-hydroxy ketones (Scheme 73). A further approach to such compounds is found in the reaction of a-ketonitrate esters with sodium acetate (Scheme 73), while aryl a-diketones are also available from a-ketoanils (prepared from the cyanide-ion-catalyzed transformation of aromatic aldimines) (70AHC(12)103). 

Thioacetals, prepared from the corresponding ketones, have also been reduced to alkenes using moderately active Raney nickel as the desulfurization agent (Scheme 37). This form of Raney nickel does not reduce the newly formed alkene or react with other isolated carbon-carbon double bonds. Note that under these conditions the saturated hydrocarbon often observed in Raney nickel desulfurizations is not formed. Similar conditions have been used for the conversion of cyclodecanone to cyclodecene. While thioacetals have also served as intermediates in the analogous conversion of enones into dienes, a mixture of diene products is obtained. For instance, dithiane generation from 17p-hydroxy-A -androsten-3-one, followed by desulfurization affords a 4 1 mixture of 17P-hydroxy-A -androstadiene and 17P-hy-droxy-A -androstadiene, respectively. ... 

The reaction of aldehydes or ketones with thiols, usually with a Lewis acid catalyst, leads to dithioacetals or dithioketals. The most common catalyst used is probably boron trifluoride etherate (BF3 OEt2). Similarly reactions that use 1,2-ethanedithiol or 1,3-propanedithiolleadto 1,3-dithiolanes, such as 18 or l,3-dithianes. " Dithioa-cetals can also be prepared from aldehydes or ketones by treatment with thiols in the presence of TiCU, SiCU, LiBp4, AKOTfls, with a disulfide RSSR (R = alkyl or aryl), or with methylthiotrimethylsilane (MeSSiMe3). " ... 

The procedure described here is an example of the use of the dithiane method for the preparation of ketones. The reactions appear to be general, and the yields are satisfactory. The dithiane method can be successfully applied to the synthesis of rings containing up to seven carbon atoms with a slight modi-fication of the procedure above. The synthesis of larger rings may require high dilution methods. ... 

Reaction of lithiodithianes with acyl chlorides, esters or nitriles leads to the formation of 1,2-dicarbonyl compounds in which one of the carbonyl groups is protected as the thioacetal. 476.243.244 Optically active amino ketones of type (69) are inepared via acyl on of dithiane with an oxazoline-prote ed (S)-serine methyl ester (Sch e 41). Optically active (S)-2-alkoxy-l-(l,3-dithian-2-yl)-l-propanenantioselective synthesis of (-)-trachelanthic acid. Enantioselective synthesis of L-glyceraldehyde involves the acylation of a dithiane glycolic acid derivative followed by bakers yeast mediated reduction. ... 

HS(CH2) SH, BFs-EtjO, CHjClj, 25°C, 12h, high yield, n -- l n -- 3 In cx,P-unsaturated ketones the olehn does not migrate to the P,y-position as occurs when an ethylene ketal is prepared." Aldehydes are selectively protected in the presence of ketones, except when large steric factors disfavor the aldehyde group, as in the example below. A TBDMS group is not stable to these conditions. Oxazolidines are converted to the dithiane in 70% yield under these conditions, but the use of methanesulfonic acid as a catalyst is equally effective. "... 

Silica gel treated with thionyl chloride has been found to be an efficient thioacetalization catalyst for the preparation of both dithianes and dithiolanes. Ketones require considerably more vigorous conditions allowing the use of the system for the selective... 

B.ii. Acyl Anion Equivalents. The most common umpolung equivalent is that for acyl anion 339, and dithianes 344 are the most common reagent used for this purpose. Dithiane 344 is prepared from an aldehyde, but ketones are also precursors (sec. 7.3.B.ii). Removal of the hydrogen adjacent to the sulfur requires a base such as n-butyllithium and the product is a-lithiodithiane (345). The acidity of this hydrogen is largely... 

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