Dithioacetal, olefination reaction

As mentioned in Section 4.2.2.6, dithioacetals can be used in coupling reactions with Grignard reagents in sequences leading to the formation of carbon-carbon single and double bonds. The metal-catalysed reactions depicted here exemplify their uses for olefination reactions, which opened the way to many useful synthetic applications [319],... 

The aldehyde function at C-85 in 25 is unmasked by oxidative hydrolysis of the thioacetal group (I2, NaHCOs) (98 % yield), and the resulting aldehyde 26 is coupled to Z-iodoolefin 10 by a NiCh/CrCH-mediated process to afford a ca. 3 2 mixture of diaste-reoisomeric allylic alcohols 27, epimeric at C-85 (90 % yield). The low stereoselectivity of this coupling reaction is, of course, inconsequential, since the next operation involves oxidation [pyridinium dichromate (PDC)] to the corresponding enone and. olefination with methylene triphenylphosphorane to furnish the desired diene system (70-75% overall yield from dithioacetal 9). Deprotection of the C-77 primary hydroxyl group by mild acid hydrolysis (PPTS, MeOH-ClHhCh), followed by Swem oxidation, then leads to the C77-C115 aldehyde 28 in excellent overall yield. 

The Lewis acid catalyst 53 is now referred to as the Narasaka catalyst. This catalyst can be generated in situ from the reaction of dichlorodiisopropoxy-titanium and a diol chiral ligand derived from tartaric acid. This compound can also catalyze [2+2] cycloaddition reactions with high enantioselectivity. For example, as depicted in Scheme 5-20, in the reaction of alkenes bearing al-kylthio groups (ketene dithioacetals, alkenyl sulfides, and alkynyl sulfides) with electron-deficient olefins, the corresponding cyclobutane or methylenecyclobu-tene derivatives can be obtained in high enantiomeric excess.18... 

It is difficult to obtain cross-coupling products of two different carbonyl compounds by an intermolecular version of the McMurry reaction. Examples that use excess amounts of one carbonyl component are few. "" When one carbonyl component is replaced by a 1,1-dihalo compound or dithioacetal and the alternative is reduced with a low-valent metal such as low-valent titanium or chromium(ii), cross-coupling products, that is, Wittig-type olefins, are produced in high yields. Because the alternative approach is described elsewhere, we concentrate on only its important features here. 

Cyanogen Iodide (ICN) has been used extensively for the cyanation of alkenes and aromatic compounds [12], iodination of aromatic compounds [13], formation of disulfide bonds in peptides [14], conversion of dithioacetals to cyanothioacetals [15], formation of trans-olefins from dialkylvinylboranes [16], lactonization of alkene esters [17], formation of guanidines [18], lactamization [19], formation of a-thioethter nitriles [20], iodocyanation of alkenes [21], conversion of alkynes to alkyl-iodo alkenes [22], cyanation/iodination of P-diketones [23], and formation of alkynyl iodides [24]. The products obtained from the reaction of ICN with MFA in refluxing chloroform were rrans-16-iodo-17-cyanomarcfortine A (14)... 

When thiols are added to substrates susceptible to nucleophilic attack, bases catalyze the reaction and the mechanism is nucleophilic. These substrates may be of the Michael type197 or may be polyhalo olefins or alkynes.169 As with the free-radical mechanism, alkynes can give either vinylic thioethers or dithioacetals ... 

Apart from the addition reaction to electrophilic olefins, the / -carbon atom of 1,1-enediamines can also substitute a,/ -unsaturated compounds carrying a leaving group. Schafer and Gewald129 have shown that 141 and 142 react with 143 to give product 144 in moderate to good yields (equation 54). Ketene dithioacetals derived from an alkyl cyanoacetate and malononitrile behave similarly to 143130. When imine 145 is employed, the reaction results in the formation of 146 (equation 55)129. Apparently displacement of ethoxy group and cyclocondensation by attack on the nitrile moiety are the key steps in the reaction. 

Interestingly, the subsequent reactions of the titanium-alkylidene species 12 obtained from dithioacetals are not limited to carbonyl olefina-tions. When the carbene complex is prepared in the presence of olefins, the latter are smoothly cyclopropanated (Scheme 8 13) [14]. Furthermore, the reaction of symmetrically disubstituted acetylenes with dithioacetals containing a methylene unit provides the corresponding trisubsti-tuted 1,3-dienes 14 in a stereoselective fashion 115]. 

Scheme 8. Reactions of the titanium-alkylidene species 12, prepared from dithioacetals, with olefins and acetylenes.

Dithiolanes, also named five-membered 1,3-dithioacetals or A,3 -acetals, find wide applications in organic synthesis, particularly in protection of carbonyl functions and their reductive conversion to hydrocarbons or olefins. Due to the stability of 1,3-dithiolanes toward various reagents and reaction conditions, they have attained an important position in this area despite the fact that dedithioacetalization to the corresponding carbonyl compounds is sometimes not an easy process. There are three general strategies that can be used for deprotection of 1,3-dithiolanes involving... 

Epoxidation of the olefin occurs with high diastereofacial selectivity to give carbamoyl-oxirane 945. This epoxide is not extremely stable, and is treated directly with methanesulfonic acid to afford the j5-D- a/o-furanoside 946. The stereocenter at C-2 must be inverted to match the configuration of the natural product. This is accomplished by triflate formation followed by an Sn2 reaction with cesium acetate. Hydrolysis of the OAc group furnishes the desired P D-ga/ac o-furanoside (947). 0-Methylation, benzyl group hydrogenolysis, acidic hydrolysis, and dithioacetal formation completes the synthesis of 948 in 11 steps and 5.7% overall yield from 929 [252]. 

Promoted by TiCU, a-oxoketene dithioacetals 281, as a special kind of activated olefin bearing two a,(3-dialkylthio substituents, reacts with aryl aldehydes to afford polyfunctionalized 1,4-pentadienes 283, rather than normal MBH adduct 282 (Scheme 2.155). In addition, a series of a-(l,3-dithiolan-2-yhdene)-p-amino carbonyl derivatives 284, the aza-MBH adducts, were obtained in good to excellent yields from novel one-pot, three-component reaction of a-oxo... 

The formation of a dithioacetal as an intermediate in organic synthesis is not new to most chemists. However, in recent years there has been a continuing improvement in the methods of preparation as well as the subsequent reactions. The early use of the dithioacetal group as a means to reduce carbonyl functions with Raney nickel has been expanded to extensive use as a protecting group, methylene blocking group and as an intermediate in the preparation of complex hydrocarbons, olefins, aldehydes and ketones. 

Reactions.—Asymmetric syntheses involving cr-sulphinyl carbanions have been described, including the preparation of /ff-methoxy-)ff-phenylacetaldehyde via a chiral dithioacetal mono-5-oxide anion " and of lactones, -hydroxy-lactones, and esters such as (i )-mevalonolactone. or-Sulphinyl carbanions are intermediates in the reaction of sulphines with carbanions (thiophilic addition) which can lead ultimately to ketones or olefins - (see also Chap. 3, Pt II, p. 162). 

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