2-benzyl-1,3-dithiane

Intermediate 10 must now be molded into a form suitable for coupling with the anion derived from dithiane 9. To this end, a che-moselective reduction of the benzyl ester grouping in 10 with excess sodium borohydride in methanol takes place smoothly and provides primary alcohol 14. Treatment of 14 with methanesulfonyl chloride and triethylamine affords a primary mesylate which is subsequently converted into iodide 15 with sodium iodide in acetone. Exposure of 15 to tert-butyldimethylsilyl chloride and triethylamine accomplishes protection of the /Mactam nitrogen and leads to the formation of 8. Starting from L-aspartic acid (12), the overall yield of 8 is approximately 50%, and it is noteworthy that this reaction sequence can be performed on a molar scale. 

The regeneration of carbonyl compounds from 1,3-dithianes can be achieved using potassium hydrogen persulfate, Oxone , supported on wet alumina <96SL767> and by periodic acid under non-aqueous conditions <96TL4331>. The deprotection of benzyl substituted 1,3-dithianes can be achieved using the one electron oxidant [Fe(phen)3](PF6)3 <96SL315>. 

Several lithium reagents have been found to convert pyridine to 2,2 -bipyr-idines in satisfactory yield. Following from the formation of 2,2 -bipyridines from 2-lithiopyridines, it has been found that 2-benzyl-2-lithio-1,3-dithiane forms 2,2 -bipyridine in 30-75% yield when refluxed with pyridine in tetrahydrofuran, " and related compounds behave similarly. Lithium diisopropylamide with pyridine in ether affords up to 50% 2,2 -... 

Another convenient method for the preparation of functionalized cyclobutanol derivatives is by treatment of 1,2-diphenylethylene acetals containing a 1,3-dithiane moiety in the y-position, e.g. 14c. with butyllithium. The isolation of 2,2-(propane-l,3-diyldisulfanyl)cyclobutanol (15c) together with benzyl phenyl ketone in 90 and 92 % yield, respectively, indicates that the reaction mechanism should involve the intramolecular attack of the metalated dithiane on the acetal carbon atom with concomitant hydride shift at the acetal group.15... 

This is another example of umpolung (see 0-95) 1478 the normally electrophilic carbon of the aldehyde is made to behave as a nucleophile. The reaction can be applied to the unsubstituted dithiane (R = H) and one or two alkyl groups can be introduced, so a wide variety of aldehydes and ketones can be made starting with formaldehyde.1504 R may be primary or secondary alkyl or benzylic. Iodides give the best results. The reaction has been used to close rings.1505 A similar synthesis of aldehydes can be performed starting with ethyl ethyl-thiomethyl sulfoxide EtSOCH2SEt.1506... 

M. Funabashi and J. Yoshimura, Branched chain sugars. Part 14. Synthesis of new branched-chain cyclitols having myo- or scyllo-, and muco-configuration from 3-< -benzyl-5,6-dideoxy-5-C-(l,3-dithian 2-yl)-6-nitro-L-idofuranose and D-glucofuranose, J. Chem. Soc. Perkin Trans, p. 1425 (1979). 

An interesting application of the 3-methoxybenzoin-based photolabile linker has been described in which the dithiane, ( )-(3- 2-(l,3-dithian-2-yl)-l-[(9-fluorenylmethoxy-carbonyl)oxy]-2-phenylethyl)benzyl)oxy] acetic acid (126, Scheme 33), a transiently masked form of the caging moiety, is incorporated into a peptide chain generated by solid-phase synthesis. 248 ... 

More reactive anions such as the 2-lithio-l,3-dithiane derivatives, phenyllithium and r-butyllithium do not require a special solvent and proceed in high yield in THF. While HMPA is known to suppress the migratory insertion to CO in anionic complexes,127 it does not deter the CO insertion in these cases no example of direct alkylation is reported. The only electrophile which adds without CO insertion is the proton, as discussed above. Good alkylating agents (primary iodides and triflates, ally bromide, benzyl... 

Purposely, as models for copolymers, the cis/trans-isomers of 2,5-disubstituted 1,3-dithianes (cf. Scheme 22) were synthesized and confor-mationally studied (02CEJ1546). The conformational equilibrium in the trans isomers always arranges the benzyl and the thienyl groups in the... 

The second synthesis of lasubine II (6) by Narasaka et al. utilizes stereoselective reduction of a /3-hydroxy ketone O-benzyl oxime with lithium aluminum hydride, yielding the corresponding syn-/3-amino alcohol (Scheme 5) 17, 18). The 1,3-dithiane derivative 45 of 3,4-dimethoxybenzaldehyde was converted to 46 in 64% yield via alkylation with 2-bromo-l,l-dimethoxyethane followed by acid hydrolysis. Treatment of the aldol, obtained from condensation of 46 with the kinetic lithium enolate of 5-hexen-2-one, with O-benzylhydroxylamine hy-... 

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... 

In a synthesis of Epothilones A and B, Danishefsky and co-workers used a triphenylsilyl ether to protect a hindered secondary alcohol in a long sequence that included DDQ deprotection of a benzyl ether, dithiane hydrolysis, dimethyl acetal hydrolysis with p-toluenesulfonic acid in dioxane-H20 (5 1) at 50 °CT... 

Single carbons can be added as cyanide using Acetone Cyanohydrin, " diethylaluminum cyanide (eq 6), or Lithium Cyanide or as methyl groups using an organocuprate (eq 7). A single carbon may be added with dithiane salts and an example of addition of a substituted 1,3-Dithiane to O-benzyl glycidol is shown in eq 8. ... 

With Methyl Iodide. Dichloroethyl sulphide reacts with methyl or benzyl iodide, forming the corresponding sulphonium salt. For instance, with methyl iodide, dithiane methiodide is formed ... 

---