2-acyl-1,3-dithiane

The value of 2-acyl-1,3-dithiane 1-oxides in stereocontrolled syntheses has been extended to the enantioselective formation of (3-hydroxy-y-ketoesters through ester enolate aldol reactions <00JOC6027>. 

The 3 + 2-cycloaddition of nitrile oxides to 2-crotyl-l,3-dithiane 1-oxides produces exclusively 5-acyldihydroisoxazoles.92 Lewis acid addition to 1,3-dipole cycloaddition reactions of mesityl nitrile oxide with a, /i-unsaturated 2-acyl-1,3-dithiane 1-oxides can reverse the sense of induced stereoselectivity.93 The 1,3-dipolar cycloaddition of 4-t-butylbenzonitrile oxide with 6A-acrylainido-6A-deoxy-/i-cyclodextrin (68) in aqueous solution favours the formation of the 4-substituted isoxazoline (69) rather than the 5-substituted regioisomer (Scheme 24).94 Tandem intramolecular cycloadditions of silyl nitronate, synthons of nitrile oxides, yield functionalized hydrofurans.95... 

Transition states for reduction according to our usual model of chelation-controlled 2-acyl 1,3-dithiane 1-oxide reactivity, together with steric approach control were proposed to rationalize the high levels of observed stereoselectivity. Previous work by Solladie suggests that ketone reduction by the DIBAL/ZnCl2 system does indeed involve such chelated transition states.15... 

While such transition-state models have helped us to rationalize the patterns of selectivity observed in other reactions of 2-acyl- 1,3-dithiane 1-oxide substrates, such clear trends are not found in conjugate addition reactions (Table 3). One simple explanation for the poorer levels of stereoselectivity may be bond rotation within the acyl substituent, allowing the enone moiety to attain conformations other than those shown in 17 and 18. 

TL 24 2009 (1983) (0-keto ester) 25 1241 (fi-diketones to /J-hydroxy ketones), 4623 (3-oxo glutarate and adipate esters), 5083 (a-sulfenyl-/J-keto esters) (1984) 26 101 (/J-keto esters), 771 (a-PhS ketone), 4213 (/J-keto esters) (1985) 27 565 (/J-diketones to /J-hydroxy ketones), 1915 (a-keto esters) 2091 (/J-keto esters), 2657 (/J-keto esters), 3547 (2-acyl- 1,3-dithianes 2-acylthiazoles), 4737 (a-chloro ketones), 4817 (a-PhSOj ketone), 5275 (/J-keto esters and amides), 5281 (/ -keto esters), 5397 (a-chloro ketone, /J-keto ester), 5405 (/J-keto thio- and dithioesters) (1986) 28 2709 (/ -chloro-a-keto ester), 3189 (/J-keto ester) (1987) 29 4769 (3- and 4-nitro ketones), 4865 (/J-keto ester), 6167 (5-acetyl-2-isoxazolines) (1988) 30 2707 (yS-keto ester), 3701, 5705 (/J-keto ester) (1989) 31 1159 (/J-keto ester), 1615 (/J-keto ester), 1811, 3631 (/J-keto esters), 4025 (a-hydroxy ketone), 4195 (2-acyl-2-alkenoate ester), 5575 (y- and 5-keto sulfones), 7463 (/J-diketone to /f-hydroxy ketone)... 

Acyl-1,3-dithianes are available by the nucleophilic thioacetalisation of ketones bearing an enolisable methylene group with 1,3-propylene bis(p-tolue-nethiolsulfonate) (mp 73 °C).187 The reaction was first applied in the Woodward-Barton synthesis of Lanosterol188 and has since been adapted to some useful synthetic procedures. For example, reaction of the enamine 94,1 [Scheme 2.94] with 13-propylene bis(/ -toluenethiolsulfonate) afforded the 2-acyl-1.3-dithiane 942 after hydrolysis of the enamine. The ability of the dithiane to sta-... 

The diastereoselective electrophilic amination of ketone enolates in 2-substituted 2-acyl-1,3-dithiane 1-oxides 19 with di-/m-butyl azodicarboxylate (DBAD) was reported recently21. The un/i-isomcr, anti-19, led to the major isomer anti-20, while. vyn-19 gave predominantly. 9171-20. 

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. 

Triketone mono-dithioacetals, 5-diketones prepared from 2-acyl-1,3-dithianes (Section... 

Figure 2 Conformation of enolate of 2-acyl-1,3-dithiane 1-oxide.

The route is based upon an acylation-oxidation-deacylation sequence, with commercially available, inexpensive 1,3-dithiane employed as the starting material. 2-Acyl-1,3-dithianes have proved to be particularly effective substrates for asymmetric oxidation in our hands,7,9,11,12 and as 2-(2,2-dimethylpropanoyl)-1,3-dithiane undergoes this asymmetric oxidation most efficiently (ca. 90% ee), it was chosen as the intermediate. 

Diastereoselective additions. The pounds exert stereodirecting effects on i the diastereoselectivity observed in the i serine orthoester and 2-acyl-1,3-dithian control. 

Diastereoselective additions. The y-substituents of allenyl carbonyl compounds exert stereodirecting effects on the Grignard reaction. On the other hand, the diastereoselectivity observed in the reactions of the aldehydes derived from a serine orthoester and 2-acyl-1,3-dithiane 1-oxides can be attributed to chelation control. 

The most expedient access to mono-dithioacetals of 3-cyclohexene-l,2-diones is by union of 2-acyl-1,3-dithianes with enones and subsequent aldolization, with the first step assisted by ZnC. ... 

Oxidative hydrolysis of an ethylene dithioketal. Cain and Welling report that the method of Corey and Erickson (4,216) for oxidative hydrolysis of 2-acyl-1,3-dithianes is also useful for unmasking of ethylene dithioketals. Thus treatment of the bisethylene dithioketal (1) with 4 eq. of NBS in 10% aqueous acetone at 0° for 20 min. selectively removes the less hindered ethylene dithioketal group at C to give (2) in 80% yield. Removal of the ethylene dithioketal group at C2 with Raney nickel requires reflux in ethanol and is accompanied by reduction of the carbonyl group. 

Oxidative hydrolysis of 1,3-dithianes using N-halosuccinimides has been extensively investigated . The yields were consistently high when using N-bromosucdnimide (NBS), usually in acetonitrile. Unlike earlier methods 2-acyl-1,3-dithianes were efficiently hydrolysed to 1,2-dicarbonyl compounds. For example, 1-phenyl-1,2-propanedione was prepared in quantitative yield from the 2-benzoyl-2-methyl-l,3-dithiane (equation 14). Silver salts often aid the reaction, but it has been noted that NBS in the... 

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