Aldehydes, preparation using 1,3-dithiane

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. ... 

The method ZC3Z + C is used for the preparation of reduced pyrimidines, oxazines and thiazines as well as for dioxanes, dithianes and oxathianes as mentioned above (e.g. 258 — 257, 259 Z, Z = NH, O, S). The Prins reaction yields 1,3-dioxanes (77S661) it involves the acid-catalyzed condensation of alkenes with aldehydes with 1,3-diols as intermediates. 

In particular, 1,3-dithiane prepared from dimethoxymethane (methylal) and pro pane-1,3-dithiol in the presence of boron trifluoride-etherate,237 and 2-alkyl-1,3-dithianes prepared similarly from aldehydes,2383 are important acyl anion equivalents. These and other uses are discussed in Sections 5.7.5, p. 596, and 6.6.1, p. 909. A wide-ranging review of the reversal of polarity of the carbonyl group through the formation of these sulphur-containing reagents has emphasised their value in organic synthesis.2388... 

Dithianes are readily prepared from aldehydes (for an overview, see 1,3-dithianes as protecting group) and offer high stability towards acids and bases. Therefore, use of the S,S-acetal unit is especially useful in multistep synthesis. A crucial step is the hydrolysis of S,S-acetals, the difficulty of which is due to the excellent nucieophilicity of sulfur. 

In the case of tiglic aldehyde (224), dithiane 225 was used, and the resulting 1,3-dihydroxyketone 226 was employed in the preparation of the furopyridine antibiotic 2-epi-CJ-16,170 (Scheme 63)355. 

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). 

The reagent is prepared by the reaction of 1,3-propanedithiol (I cq.) with malondi-aldehyde bisdimethylacetal (Aldrich), in a manner similar to that used for synthesis of 1,3-dithiane. ... 

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). " ... 

There are several procedures available for the preparation of acylsilanes. A general synthesis of acyl silanes is via the dithiane route.Hydrolysis of 2-silyl-l,3-dithianes which leads to acyl silanes can be accomplished with mercury(II) salts. To repress formation of aldehyde by-products, various modifications for the deprotection of silyl dithi-anes have been reported, including the use of HgO-F3B OEt2 or chloramine-T. ... 

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. "... 

C—C Bond formation. s-Trithiane has been used very much like 1,3-dithiane (2, 182-187) in organic synthesis 2-3 hojvever, the carbanion derived from this reagent tends to undergo carbenoid decomposition. Metalated trithiane reacts readily with primary halides to give 2-alkyl-s-trithianes convertible into aldehydes, as shown for a preparation of n-pentadecanal 1... 

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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