Dithiane Derivatives

Benzo analogs of 381 were obtained in a Friedel-Crafts reaction from 2,3-dicyano l,4-dithiin-5,6-dicarboxylic acid anhydride and benzene (62MI2), or from 2,3-dichloro-1,4-naphthoquinone and 1,2-dimercaptoethane (67RC1067). Reduction potentials of several quinones were determined (86CC1489). 

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Reaction of the anion derived from the tosyl imide of l,3,S-trithiane with alkyl iodides gives a mixture of the mono- and di- alkylated products, in which anti stereochemistry predominates. The analogous 1,3-dithiane derivative is only monoalkylated <96JCS(P1)313>. 

Dithiin and 1,3-Dithiane Derivatives Thermal and Photochemical Reactions Reactions with Electrophiles Reactions with Nucleophiles... 

The C-H bond-dissociation energies Z>c-h of the acetals 130 and 131, monothioacetal 132, and the dithioacetal 133 (Figure 7) were calculated from experimental reaction kinetic data <2005MI379>. The C-H dissociation energies of the 1,3-dithiane derivative 133 proved to be lowest, followed by the 1,3-oxathiane derivatives 132,... 

The most general approach to the synthesis of acyl silanes is based on hydrolysis of 2-silyl-l,3-dithioacetals, first investigated for 1,3-dithiane derivatives by Brook56 and Corey57 in the late 1960s (Scheme 3). Oxathioacetals and protected hemithioacetals have also been used, and some formyl silanes have been isolated by hydrolysis of dioxa-acetals (vide supra). 

Oxidative hydrolysis of 1,3-ditkiane derivatives. The oxidative cleavage of 1,3-dithiane derivatives to the parent carbonyl compounds can be effected by reaction with Pb02 in aqueous THF in the presence of BF3 etherate or HC104 (equation I).1... 

One of the most direct methods of synthesizing acylsilanes involves deprotonation and silylation of the 1,3-dithiane derivative of an aldehyde. Unmasking the carbonyl group reveals the acylsilane (Figure Si6.4). 

The second synthesis of lasubine II (6) by Narasaka et al. utilizes stereoselective reduction of a /3-hydroxy ketone O-benzyl oxime with lithium aluminum hydride, yielding the corresponding syn-/3-amino alcohol (Scheme 5) 17, 18). The 1,3-dithiane derivative 45 of 3,4-dimethoxybenzaldehyde was converted to 46 in 64% yield via alkylation with 2-bromo-l,l-dimethoxyethane followed by acid hydrolysis. Treatment of the aldol, obtained from condensation of 46 with the kinetic lithium enolate of 5-hexen-2-one, with O-benzylhydroxylamine hy-... 

Interestingly, deprotection (hydrolysis) of the heterocyclic auxiliary exposes a synthetically useful carbonyl group. This is possible in our system since the auxiliary is bonded to the carbonyl group by a carbon atom rather than a heteroatom. Such hydrolyses are well established for 1,3-dithiane derivatives as a result of their ubiquity as synthons for umpolung reactivity of the carbonyl group (Fig. I).5... 

Asymmetric sulfoxidation of2-acyl-1,3-dithianes Preparation of optically pure DiTOX substrates. The preliminary investigations of 1,3-dithiane derivatives as asymmetric building blocks and chiral auxiliaries described in this review... 

Under the optimum reaction conditions, reactions of the 2-stannyl-1,3-dithiane derivatives 16,18,19 with various olefinic compounds were carried out and the results are shown in Table 3. 

Acyclic dithioketals and 1.3-dithianes derived from aromatic ketones give acceptable yields. 

The 1,3-dithianes derived From aromatic ketones give comparable yields in this reaction di-fluorodiphenylmethane is obtained in 49% yield, while bis(4-chlorophenyl)difluoromethane... 

In Scheme 1.3, hexanal on reaction with 1,3-propanedithiol gives the 1,3-dithiane derivative 1.8. A strong base such as u-butyllithium abstracts the proton to give the corresponding 2-lithio-1,3-dithiane 1.9, which reacts with 1-bromopentane to give alkylated product 1.10. Treatment of 1.10 with FIgO and BF3 (boron trifluoride) in aqueous THF (tetrahydrofuran) yields the dipentyl ketone (the corey-seebach reaction ). Thus, dithianyllithium (2-lithio-1,3-dithiane) 1.9 is an acyl anion synthetic equivalent. 

Open chain and cyclic thioacetals 1,3-Dithiolane and 1,3-dithiane derivatives are versatile intermediates in the synthesis and interconversion of monocarbonyl and 1,2-dicarbonyl compounds. Protection of carbonyl groups as their open-chain and cyclic thioacetals is an important method in the synthesis of organic molecules. Thioacetals are stable... 

Acyclic dithioketals and 1.3-dithianes derived from aromatic ketones give acceptable yields. 1,3-Dithiolanes are fluorinated in very low yields. Electron-accepting substituents in the para-position favor fluorination, whereas electron-donating groups lower the yields (Table 13). 

Dithioacetals of aldehydes are sources of carbanions and hence may be used to form new C-C bonds in reactions in which the formerly electron-deficient character of the aldehydic carbon has been reversed. The 1,3-dithianes derived from formaldehyde or a higher aldehyde may be metallated and then alkylated (Scheme 2.27). Hydrolysis of the dithioac-etal is usually carried out in the presence of a thiophilic (sulfur seeking) metal salt such as a mercury salt. The insoluble sulfides cause the equilibrium to move in favour of the parent carbonyl compound. 

Oxidative hydrolysis of 2-aeyl-l -dithiane derivatives. A study of the hydrolysis of 2-acyl-1,3-dithianc derivatives by mercuric chloride (HgCl ) has been published. However, hydrolysis of 2-acyl-l,3-dithianes is slow. In this case use of N-haiosuccini-mide reagents is recommended. Either N-bromo uccinimide or N-chlorosuccinimidc-silver nitrate is suitable for oxidative hydrolysis of 1,3-dithiane derivatives. The N-halosuccinimide reagents are useful for hydrolysis of 2-acyl-1,3-dithianes to 1,2-dicarbonyl compounds. 

In contrast, the unexpected hydrogenolysis of a tertiary alcohol was observed during the desulfurization either of 1,3-dithiane derivatives or of their monosulfoxides, as exemplified in Scheme 3. It is intriguing that even deactivated W-2 Raney Ni did not improve the result, but a low temperature did allow convenient desulfurization with a minimum amount of side product. 

The mechanism of this transformation has been investigated [135, 136]. In the absence of nucleophiles and using carefully dried MeCN, the oxidation step of 1,3-dithiane derivatives corresponds to an EEC process involving one electron per molecule. To rationalize this process, the formation of a dication (XXX +) is suggested, which supposedly exists in equilibrium with a dimer (XXXI) originated by the reaction of XXX with the starting material (XXX) [Eq. (85)] [135]. 

A convenient, electrochemically based procedure for regenerating aldehydes and ketones from their 1,3-dithiane derivatives was developed [137] ... 

The proof given in support of dianion formation does not however seem to be sufficients Nevertheless the single step process is reasonably efficient when primary alkyl halides are used but none of the dialkylated compound is produced with isopropyl iodide and benzyl bromide. 2-(o>-Haloalkyl)-l,3-di-thianes have proved to be valuable precursors of 1,3-dithianes derived from cyclic ketoncs. Haloge-nated 1,3-dithianes have been in turn prepared from 2-lithio-l,3-dithiane and stoichiometric amounts of u-chloro- or bromo-alkyl iodides or with an excess of the corresponding dichloride (Scheme 64, entry c). Use of u-bromoalkyldithianes is often impractical because of the ease with which these compounds are transformed into cyclic sulfonium salts. ... 

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]. 

Carbanions of type (2) or type (4) also react readily with 1,2-oxides to form 1,3-dithiane derivatives of /3-hydroxyaldehydcs (from type 2) or /J-hydroxyketones (from type 4). For example, the carbanion (7) reacts with styrene oxide to give (8) in 70% yield on hydrolysis and dehydration (8) is converted into benzylideneacetone... 

It could be established that the hydrolysis of 1,3-dithianes derived from pc/ra-substi luted acetophenones (4) is promoted by silver ions. Kinetic study using a 10% (v/v) diox-ane/water solvent shows that, when [Ag+] <0.2 mol L 1, the p-NC)2, —Cl, —H and —Me derivatives hydrolyze via rapidly formed 1 Ag+ 1 dithiane complexes, but that the / -McO derivative forms an unreachve 1 1 complex and hydrolyses via a 2 Ag+ 1 dithiane complex. Comparison of the kinetic parameters with those available for analogous open-chain 5,5-acetals reveals that cychzahon leads to a substantial (>104-fold) overall loss of reactivity and that this loss arises both from a lowering of acetal basicity toward Ag+ and from a slower rate of hydrolysis of the 1 1 complex. The imphcations for hydrogen ion-catalyzed hydrolysis of cychc acetals have been discussed, as have the reasons for the lower reactivity of the cychc acetals343. 

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