Dithioacetals, cyclization

The synthesis of 3-acyl- and 3-aroyl-l,2-benzisoxazoles was accomplished by the desulfurization of (562). The dithioacetal (562) was prepared by the addition of the lithium salt of propenedithioacetal to an isocyanate with subsequent base cyclization (equation 61) (B-79MI41609). 

Nitroketene dithioacetal reacts with anthranilic esters to afford quinolone derivatives, which are converted into diazepinones by reductive cyclization. The review by Kolb covers synthetic application of nitroketene dithioacetal for heterocyclic compounds (see Scheme 10.26).145... 

The a-oxoketene dithioacetal 6.40 is derived from indoxyl (l,2-dihydroindol-3-one), a heterocyclic carbonyl precursor, and its reaction with simple allyl anions will also yield the corresponding Jl-annulation product. Thus when 6.40 was reacted with allyl anions 65 the corresponding carbinol acetals 66 formed insitu underwent smooth BF3.Et20 assisted cyclization to afford the corresponding carbazoles 67 in high yields <99T11563>. 

Another route involves a palladium-copper-catalyzed tandem carbon-carbon formation/cycloaddition sequence (Equation 12) <2005TL8531>. Notably, cycloadditions of azide to the internal alkynes failed under click chemistry reaction conditions <2003DDT1128>. Cyclization under oxidative conditions has been reported from dithioacetal 163 (Equation 13) <1996TL3925>. The formation of 164 as a single diastereoisomer has been explained by stereoelectronic effects. 

The dithiane derivative 60 (Scheme 14) is such a compound, it being made from 2,3 5,6-di-0-isopropylidene-D-mannose by treatment with 2-lithio-l,3-dithiane to give a heptose dithioacetal that was refunctionalized at C-2-C-3 by way of the C-l anion and then converted to the 6,7-epoxide following selective acid-catalyzed cleavage of the 6,7-acetal ring. Treated with n-butyllithium it gives, in 70% yield, the cyclized 61, which is efficiently convertible into validatol 62, a component of validamycin A, by desulfurization with Raney nickel and de-O-protection by use of boron tribromide in dichloromethane [31]. 

Methyl-5-oxo-l,5-dihydro-8-carbamoyl-l,2,4-triazolo[4,3-c]pyrimidines 577 and 578 were prepared by the cyclization of 576 with acetic anhydride and ethyl oxalate, respectively (89PHA604).The 4-methyl-l,2-dihydropyra-zolo[3,4-d]pyrimidine-3,6-dione 579 also was obtained in the latter case, as a consequence of breaking the amide bond and releasing the amine moiety. Coupling ethyl dithioacetate and 5-chloro-4-hydrazinopyrimidine (580) afforded the triazolo[4,3-c]pyrimidine 581 (89H239) (Scheme 114). 

Thus, when the aldopentose diethyl dithioacetals are treated with 1 mole of p-toluenesulfonyl chloride in pyridine, cyclization to form a 2,5-anhy-dride is observed in each instance except in the arabino series, where a 5-O-p-tolylsulfonyl derivative can be isolated. It may be supposed (23) that the energy of activation for the cyclization reaction, being the difference between the ground-state and the transition-state energies, is smaller in those stereoisomers where conformational factors bring 0-2 into close... 

The copper(I)-catalyzed addition of Grignard reagents to P-(alkylthio)-a,p-unsaturated esters is the preferred protocol for substitution of the alkylthio substituent, e.g. (310 - 311),21 while potassium enolates add to a-ketoketene dithioacetals, e.g. (312 — 313), without dialkylation (Scheme 96).218b,c Further, Hanessian reports an expedient synthesis of penam (315) via intramolecular cyclization of the (3-lactam nitroalkene (314), but loss of the methylthio moiety does not occur spontaneously (Scheme 97).219... 

D. ASSEMBLING THE BRIDGED BCDE RING TANDEM CYCLIZATION AND INTRAMOLECULAR ALKYLATION OF A DITHIOACETAL... 

Ring cleavage of a-alkenoyl cyclic ketene dithioacetals by dimsyl sodium generates a thiolate anion and induces an intramolecular Michael cyclization which produces 2,3-dihydrothiopyran-4-ones n good yields (Scheme 218) <2000SL1804, 2007S2115>. 

---