Aldehydes 1.3- oxathiolanes

The most commonly used protected derivatives of aldehydes and ketones are 1,3-dioxolanes and 1,3-oxathiolanes. They are obtained from the carbonyl compounds and 1,2-ethanediol or 2-mercaptoethanol, respectively, in aprotic solvents and in the presence of catalysts, e.g. BF, (L.F. Fieser, 1954 G.E. Wilson, Jr., 1968), and water scavengers, e.g. orthoesters (P. Doyle. 1965). Acid-catalyzed exchange dioxolanation with dioxolanes of low boiling ketones, e.g. acetone, which are distilled during the reaction, can also be applied (H. J. Dauben, Jr., 1954). Selective monoketalization of diketones is often used with good success (C. Mercier, 1973). Even from diketones with two keto groups of very similar reactivity monoketals may be obtained by repeated acid-catalyzed equilibration (W.S. Johnson, 1962 A.G. Hortmann, 1969). Most aldehydes are easily converted into acetals. The ketalization of ketones is more difficult for sterical reasons and often requires long reaction times at elevated temperatures. a, -Unsaturated ketones react more slowly than saturated ketones. 2-Mercaptoethanol is more reactive than 1,2-ethanediol (J. Romo, 1951 C. Djerassi, 1952 G.E. Wilson, Jr., 1968). 

A somewhat similar method to that mentioned above involves alkylation of 4,4-dimethyl-1,3-oxathiolane 5,5-dioxide 32 at the 2 position followed by FVP at 400°C, which results in fragmentation with loss of SO2 and isobutene to give the aldehydes 33. Other electrophiles that may be used include aldehydes, ketones, and McsSiCl, making this a convenient formyl anion equivalent (79TL3375). 

Smaller aldehydes form cyclic acetal-type oligomers readily in aqueous conditions.60 Diols and polyols also form cyclic acetals with various aldehydes readily in water, which has been applied in the extraction of polyhydroxy compounds from dilute aqueous solutions.61 E in water was found to be an efficient catalyst for chemoselective protection of aliphatic and aromatic aldehydes with HSCH2CH2OH to give 1,3-oxathiolane acetals under mild conditions (Eq. 5.7).62... 

Other valuable substrates for the domino Knoevenagel/hetero-Diels-Alder reaction are chiral oxathiolanes such as 2-778, which are easily accessible by condensation of 2-thioacetic acid and a ketone in the presence ofpTsOH, followed by oxidation with hydrogen peroxide [390]. As described by Tietze and coworkers, the Knoevenagel condensation of 2-778 with aldehydes as 2-777 can be performed in... 

For preparative purposes, the reaction of thiocarbonyl ylides with carbonyl compounds can be considered as an alternative method for the synthesis of 1,3-oxathiolanes. Aromatic aldehydes, chloral, glyoxalates, mesoxalates, pyruvates as well as their 3,3,3-trifluoro analogues are good intercepting reagents for thioketone (5)-methylides (36,111,130,163). All of these [3 + 2] cycloadditions occur in a regioselective manner to produce products of type 123 and 124. 

The desUylation strategy has been used for the cycloaddition of the parent thiocarbonyl yhde la with aldehydes and reactive ketones. The product obtained using A-methyl-3-oxoindolinone as the trapping agent corresponds to the spiro-cyclic compound 125 (168). Thioketene (5)-methylide (127) was reported to react with aromatic aldehydes and some ketones to furnish 2-methylene-substituted 1,3-oxathiolanes (128) (51) (Scheme 5.42). 

Oxathiolane 3,3-dioxide (332) metallates in its 2-position to yield an anion which reacts with various electrophiles (alkyl halides and carbonyl compounds) to give substituted oxathiolanes (333) in good to excellent yield (79TL3375). Pyrolysis of these alkylated products affords the corresponding aldehydes or 2-hydroxyaldehydes in addition to sulfur dioxide and isobutylene (Scheme 71). The oxathiolane (332) thus becomes another member of the already burgeoning class of carbonyl anion equivalents. 

Oxathiolanes (11) are formed from aldehydes and ketones by reaction with 2-mercaptoethanol (HS-CH2-CH2OH) in the presence of, for example, zinc chloride-sodium acetate in dioxane solution at room temperature,139 or boron trifluoride-etherate.140 They are more stable to an acidic medium than the 1,3-dithianes, and therefore may be the protective group of choice in certain instances. 

Oxathiolane 2,2-dioxide undergoes metallation with n-butyllithium as expected at the 3-position (81JOC101). The anion may be alkylated with alkyl halides or carbonyl compounds. The isomeric 1,3-oxathiolane 3,3-dioxides also undergo metallation ortho to the sulfone and, when the 4-position is blocked, metallation at the 2-position may be used as an efficient conversion of alkyl halides into aldehydes as shown in Scheme 22 (79TL3375). 

Dithio ane 1,3-Dithiane 1,3-Oxathiolane Acyclic and cyclic acetals are stable to base but removed with acid. Aliphatic aldehydes are more reactive than aromatic aldehydes, which in turn are more reactive than ketones. 

Comprehensive review chapters on 1,3-oxathiolium salts <02MI35> and 1,3-oxaselenolium salts <02MI93> have appeared. Scandium triflate has been introduced as an efficient catalyst for reaction of aldehydes with mercaptoethanol to form 2-substitued 1,3-oxathiolanes <03S2503>. Protection of a-mercaptocarboxylic acids is readily achieved by... 

Renunal of ethylene hemithioacetal and -ketal protecting group, 1,3-Oxathiolanes when treated with chloramine-T in water or ethanol under mild conditions give the corresponding aldehydes or ketones in good yields. For example, 1,4-oxathiaspiro-[4.4]nonane (1) affords cyclopentanone (2) in 91 % yield when treated with chloramine-T in 85 % CHjOH-HjO at 25° for 2 min. 

Isocyanides react with 2-phthalimidosulfanylphenols to give 2-imino-l,3-benzoxathioles (Equation 63) <2003S662>, and water-soluble 4-imino-l,3-oxathiolane derivatives have been formed by reaction with diiodo-methane followed by a silver or lead salt (Equation 64) <2005S2946>. A convenient route to oxathiolanes from 2-hydroxyalkyl /t-butyl sulfides and aldehydes has appeared (Equation 65) <2006T931>. 

Other approaches to the key carbonyl ylide intermediates are also effective and Sml2 treatment of an a-iodo silyl ether in the presence of an aldehyde also gives the dioxolane product (Equation 78) <1996JA3533>. Similarly, desilylation of 219 gave an intermediate that added to carbonyl compounds to give dioxolanes and to thioketones to give oxathiolanes (Scheme 21) <1996SL234>. 

Efficient deprotection of thioketals to the corresponding ketones can be induced by photosensitized single electron transfer to n-acceptors such as 9,10-dicyanoanthracene. Similar reactions are observed for oxathiolanes, but the method is unsatisfactory for protected aldehydes. 

The fluoride ion-catalyzed addition of alkoxymethylthiomethylsilanes to aldehydes followed by acid-catalyzed cyclization affords 1,3-oxathiolanes (Scheme 10.220)... 

From an aldehyde, acetal or ketal HS(CH2) SH, CH2CI2, NBS, rt, 57-91% yield. This method was also used to prepare oxathiolanes. 

Ytterbium triflate in an ionic liquid is an efficient catalyst for reaction of aldehydes and ketones with mercaptoethanol to form 2-substituted 1,3-oxathiolanes <04SL2785> and K-10 montmorillonite has been used for the same reaction where it shows selectivity for aldehydes over ketones <04SL1592>. The compound 76 has been used to introduce a mercapto acid unit into peptide analogues <04S1088> and the diastereoselectivity of addition of the anion of 77 to carbonyl compounds has been examined <03JHC979>. 

A three-component expeditious synthesis of 3,6-diaryl-5-mercaptoperhydro-2-thioxo-l,3-thiazin-5-ones from 2-methyl-2-phenyl-l,3-oxathiolan-5-one, an aromatic aldehyde, and an N-aryldithiocarbamic acid has recently appeared [194]. The synthesis is diastereoselective and involves tandem Knoevenagel, Michael, and ring transformation reactions occurring under solvent-free MW irradiation conditions in a single pot (Scheme 8.81). 

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