1.3- Dithiane, 2-methoxy

The pivotal step in this sequence is an electrophilic substitution on indole. Although the use of l,3-dithian-2-yl carbanions is well documented, it has been shown only recently that 1,3-dithian-2-yl carbenium ions can be used in a Priedel-Crafts type reaction. This was accomplished initially using 2-methoxy-l,3-dithiane [1,3-Dithiane, 2-methoxy-] or 2-metlioxy-l,3-dithiolane [1,3-Dithiolane, 2-methoxy-] and titanium tetrachloride [Titanate(l —), tetrachloro-] as the Lewis acid catalyst.9 2-Substituted lysergic acid derivatives and 3-substituted indoles have been prepared under these conditions, but the method is limited in scope by the difficulties of preparing substituted 2-methoxy-1,3-dithianes. l,3-Dithian-2-yl carbenium ions have also been prepared by protonation of ketene dithioacetals with trifluoroacetic acid,10 but this reaction cannot be used to introduce 1,3-dithiane moieties into indole. 

C7H4IO2 88-67-5) see Chlorprothixene laS-laR (l , 3S ),p/f, 8S ]]-a-(4-iodo-l-methoxy-3-methylbutyl)-P-niethoxy-g-methyl-l,3-dithiane-2-butanol (C, .H7 IOjS2 118246-96 ) see Tacrolimus... 

Sauriol-Lord and St-Jacques (64) have studied 2,4-benzodithiepin 78 and the substituted derivatives 79-82 (Fig. 14). They found that these compounds exist in the chair form 39 (0=S) (Fig. 8), except for the derivative 82 where 13% of the twist-boat 40 (0=S) was detected. The fact that essentially only the chair form was observed in these compounds would simply be due to the long C - S bonds which attenuate the effects of steric repulsions in conformer 39 (0 =S). This is in accord with the fact that in contrast to 2-methoxy-l,3-dioxane which exists as a 7 3 mixture of equatorial conformer 83 and axial conformer 84, 2-methoxy-l,3-dithiane has been found to exist solely in the axial form 85. 

Dichloropyrazine gave 2-chloro-6-[m-methoxy-a, a-(trimethylenedithio)-benzyl]pyrazine (196), the acetal of an acylpyrazine [2-(m-methoxyphenyl)-1,3-dithiane anion (made in situ), 2-Me—THF, -100 — 20°C 14%].1482 2-Chloropyrazine gave several Ni or Pd complexes.566,581 Also other examples.374,882... 

H3C—CHC1 —CHC1 — COOR + 2,5-(OH)2— 1,4-dithian] 2-Formyl-5-methoxy- E3, 121... 

Sainsbury and co-workers (121) have synthesized several ellipticine dimers tethered through the C-5 methyl group (333) (Scheme 53) or the C-9 position (334). The 9-methoxy derivative of 333 was also prepared. The nitrile 329 was available from the Sainsbury ellipticine synthesis (122) and was transformed into the alkaloid 17-oxoellipticine (148). A clever maneuver was to add nitric acid to protonate the pyridine nitrogen of 330. This precluded A-oxide formation during dithiane hydrolysis. Reductive amination in two steps afforded the amine 332. Coupling with adipic acid gave the target bisellipticine 333. 

Our own investigations involved 5-methoxy- and 5-methylthio-1,3-dithianes (Scheme 5, X S, Y=0 or S) the corresponding 1,3-dioxanes had been studied previously (17). 

---