Ketones, from dithianes

The preparation of dithianes from enamines by reaction with trimethylene dithiotosylate (propane-1,3-dithiol di-p-toluenesulfonate) has been applied with enamines derived from oholostan 3 one, aceto-acetic ester, and phenylacetone.6 7 Reactions of trimethylene dithiotosylate with hydroxymethylene derivatives of ketones also give rise to dithianes thus the hydroxymethylene derivative of cholest-4-en-3-one can be converted to 2,2-(trimethylenedithio)cholest-4-en-3-one. 1,3-Dithiolanes are obtained in a similar manner by reaction of ethylene dithiotosylate1 with the appropriately activated substrate.5,7... 

New reaction conditions for the odorless transacetalization providing 1,3-dithianes from aldehydes or ketones, as depicted in Scheme 108 (Section 8.11.10.1), have been published <2006S3801, 2007SC993>. 

Dithianes are extremely important compounds in organic synthesis because going from ketone to thioacetal inverts the polarity at the functionalized carbon atom. Aldehydes, as you are well aware, are electrophiles at the C=0 carbon atom, but dithioacetals, through deprotonation to an anion, are nucleophilic at this same atom. 

Dithiolanes and dithianes derived from ketones are more reactive than the aldehyde-based substrates. For electron-rich aromatic compounds the use of 7V-iodosuccinimide instead of A -bromosuccinimide or 1,3-dibromo-5,5-dimethylhydantoin is recommended to avoid ring bro-mination. 

Hydrolytic cleavage of the C-O bond of bicyclic, tetracyclic, and steroidal enolates with HF-SbFs induces their isomerization to the corresponding ketones (Scheme 14.41) [104]. Rearrangement of dienones to aromatic compounds is also promoted by HF-SbFs (Scheme 14.42) [105]. Ring expansion of methyl penicilli-nates is achieved by SbCls to give thiazepine derivatives [106]. 1,3-Dithianes derived from ketones and aldehydes are deprotected with SbCls by means of a single-electron-transfer mechanism [107]. 

The addition of enolates derived from ketones and esters to 2-alkylidene-l,3-dithiane... 

The formation of 1,3-dithianes from hydroxymethylene compounds, which are enol tautomers of j3-keto aldehydes, has been shown to be useful in itself. When followed by desulphurization the net reaction is the decar-bonyladon to the ketone. This has been used to advantage in the formation of the methyl ketone (17) in equation (24). Similarly the methyl ketone (18) was formed from its hydroxymethylene derivative. ... 

For this part, we took guidance from a very well-researched review by Pihko. ° Methods for direct conversion of 87 to 93, that is, treatment with HF pyridine, aq. HF, or HCl, were first investigated. These provided only traces of the cyclized material 93 (Scheme 16). We resorted to a stepwise approach by first unmasking the ketone functionality (i.e., 92) by deprotecting the dithiane 87. Ketone 92 was then bombarded with a variety of acids (e.g., aq. HF, CSA) under a wide variety of conditions only to also afford trace amounts of the target 93 (Scheme 16). 

Other carbanionic groups, such as acetylide ions, and ions derived from a-methylpyridines have also been used as nucleophiles. A particularly useful nucleophile is the methylsulfinyl carbanion (CH3SOCHJ), the conjugate base of DMSO, since the P-keto sulfoxide produced can easily be reduced to a methyl ketone (p. 549). The methylsulfonyl carbanion (CH3SO2CH2 ), the conjugate base of dimethyl sulfone, behaves similarly, and the product can be similarly reduced. Certain carboxylic esters, acyl halides, and DMF acylate 1,3-dithianes (see 10-10. )2008 Qxj(jatjye hydrolysis with NBS or NCS, a-keto aldehydes or a-... 

The procedure for the preparation of a dithiolane from a hydroxy-methylene derivative of a ketone and ethylene dithiotosylate (ethane-1,2-dithiol di-p-toluenesulfonate) can be varied to produce dithianes when the latter reagent is replaced by trimethylene dithiotosylate.8,4 The dithiotosylates also react with enamine derivatives to produce dithiaspiro compounds.4,5... 

An effective and mild electrocatalytic procedure for the deprotection of the 1,3-dithiane group of (68), giving the ketone (67), has been developed by using a small amount of tris(/ -tolyl)amine as a homogeneous electron-transfer catalyst (Scheme 26) [86]. The scope and limitations are discussed in detail [87]. The method can be applied also for oxidative removal of the 4-methoxybenzyl thioether protecting group from poly-cystinyl peptides [88]. 

Dithioketals, especially the cyclic dithiolanes and dithianes, are also useful carbonyl-protecting groups. These can be formed from the corresponding dithiols by Lewis acid-catalyzed reactions. The catalysts that are used include BF3, Mg(03SCF3)2, Zn(03SCF3)2, and LaCl3.100 S-Trimethylsilyl ethers of thiols and dithiols also react with ketones to form dithioketals.101... 

Problem 15.14 Synthesize (a) p-methoxybenzaldehyde from benzene (b) cyclohexylethanal by hydrobora-tion and oxidation (c) phenylacetaldehyde, using 1,3-dithiane (d) phenyl n-propyl ketone from a dithiane (e) cyclohexyl phenyl ketone from PhCOOH and RLi (/) 2-heptanone, using a cuprate ... 

The stoichiometric equivalents of halofluorides have been recently applied to transform alkylene dithioacetals into gcm-difluorides.70-71 Dithioacetals such as 1,3-dithiolanes and 1,3-dithianes arc readily obtained from the corresponding carbonyl compounds by the reaction with ethane-1,2-dithiol or propane-1,3-dithiol in the presence of the complexes boron trifluoride-bis(acetic acid) or boron trifluoride-diethyl ether. Using a two-step procedure, a range of aldehydes and ketones can be converted into gem-difluorides under mild conditions. 

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