Chloral regioselectivity

The Ti(0 Pr)2Cl2/D-DIPT poison has also been used for the Ti(0 Pr)2Cl2/ BINOL-catalyzed asymmetric carbonyl-ene reaction with chloral (Scheme 8.8). With the Ti(0 Pr)4/D-DIPT poison in a 1 3 ratio, both the regioselectivity and the enantioselectivity of the ene product are improved. 

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 cycloaddition of chloral with 3,3-dimethyl-l-butene to form a good yield of oxetanes can be effected with aluminum chloride catalysis (equation 101). This reaction, however, is not regioselective (72GEP2133564). 

Chloral or benzaldehyde in the presence of dehydrated alumina48 and Al(OtBu)3 in the presence of f-BuOOH,49 are oxidizing systems reminiscent of Oppenauer oxidations that can perform regioselective oxidations of secondary alcohols. 

Diazo Compounds. Diazomethane reacts immediately with 1 dissolved in diethyl ether in a regioselective manner to give 2,5-dihydro- 1,3,4-thiadiazole (17) as a relatively stable sohd. This confound is a superior precursor of the reactive thiocarhony 1 5-methylide (8, eq 9) as it smoothly eliminates nitrogen at 45 °C. In the absence of an appropriate interceptor, thiirane 9 is formed. In the presence of electron-deficient dipolarophiles, diverse five-membered spiro-heterocycles (18) are formed via 1,3-dipolar cycloaddition (eq 9).22.23 Representative examples of dipolarophiles leading to 18 in high yield are DMAD, TV phenyl maleinimide, chloral, dimethyl azodicarboxylate, adamantanethione, as well as 1.21... 

The formation of 1,3-oxathiolane with chloral and 1,3-dithio-lanes with cycloaliphatic thioketones occurs regioselectively to yield the sterically less hindered products. On the other hand, aromatic thioketones, e.g., thiobenzophenone or 9/ fluorene-9-thione, intercept 8 to give comparable amounts of both regio-isomeric adducts. Usually, stereoisomeric dipolarophiles such as fumaronitrile and maleonitrile as well as dimethyl fumarate and maleate form 18 in a stereoselective manner. However, in the case of extremely electron-poor dipolarophiles, e.g., dimethyl 1,2-dicyanofumarate or ( )-l,2-bis(trifluoromethyl)ethylene-l,2-dicarbonitrile, non-stereospecific formations of the corresponding tetrahydrothiophenes are described. i- s This result is interpreted in terms of a stepwise reaction mechanism with a zwitterion as the key intermediate. Alternatively, this intermediate can cyclize to form seven-membered ketenimines of type 20. With R = Cp3, this product can be isolated in a crystalline form, whereas in the case of R = CN, stable lactam 21 is obtained only after addition of water (eq 10). 

The intramolecular addition of a hemiacetal hydroxy-group to a neighbouring double bond in the presence of mercuric salts can be used to effect regioselective hydration of the double bond. Thus treatment of (490) with chloral and mercuric trifluoracetate in dry THF, followed by demercuration with sodium borohydride, gave (491) in good yield. The trichloroacetal group may be removed by treatment with a sodium dispersion in dry ether or zinc in refluxing acetic acid. ... 

It is known that reaction of metal phenolates with aldehydes or ketones proceeds in regioselective manner to afford ortho-substituted hydroxyalkylation products. Bigi and coworkers reported the chiral examples of this reaction using chiral aluminum Lewis acid prepared in situ from a chiral alcohol and 1 equivalent diethylaluminum chloride. Thus, after treating phenol with the chiral Lewis acid, the resulting aluminum phenolate is reacted with chloral in toluene as shown in Scheme 6.15... 

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