Tosylate reductive removal

These key intermediate is accessible from triacetyl-D-glucal 38 in a large-scale adaptable 5-step sequence in an overall yield of 30 % conversion of 38 into hexenoside 39 according to a known two-step procedure (55), tosylation to the chloro-tosylate 40, since the chloride ions formed during the reaction in situ displace the activated allylic tosyloxy function, and, finally, the consecutive reductive removal of tosyloxy- and chloro groups 40 -> 35 (56,57) ... 

In the previous subsection, it was shown that the Ferrier reaction offers an opportunity to convert glycal derivatives into unsaturated sugar derivatives, which have an isolated double bond between C(2) and C(3). The Tipson-Cohcn reaction is another important reaction for the introduction of isolated double bonds.29 In this procedure, a cis or tram diols are converted into disulfonates (mesylates or tosylates) which are reductively eliminated with sodium iodide and zinc in refluxing DMF (Scheme 3.6a). In this reaction, the C(3) sulfonate is substituted by an iodide, which then is reductively removed by zinc with concomitant elimination of the second sulfonate moiety, introducing a double bond. Stereoelectronic effects make nucleophilic substitutions at C(3) more favourable than similar reactions at C(2) (see Section 3.2.3). Probably, the elimination proceeds through a boat conformation. In this case, the iodide and tosylate are in a syn relation. In most cases, E2 elimination proceeds via a transition state involving an anti orientation. Nevertheless, syn elimination becomes the dominant mode of reaction when structural features prohibit an anti orientation. 

The form in which these entities are supplied varies according to the reagent used. Lithium aluminium hydride provides the proton and electrons simultaneously by donating a hydride ion (H") in a reductive process probably analogous to a normal Sn3 substitution. No systematic study of such reactions appears to have been made in the steroid field, although there are numerous examples of reductive removal of halide and tosylate groups for preparative purposes. 

Reduction of alkyl halides and tosylates. - Reduction with sodium cyanoborohydride in HMPT provides a rapid and selective removal of iodo. bromo, and tosyloxy groups in high yield. Thus 1-iododecane can be reduced in thi.s way to n-deeane in... 

Desulfonylation. Various sulfonyl groups are reductively removed by Mg/MeOH. These include alkenyl sulfones, alkyl tosylates, and A -Boc-arenesulfonamides (p-toluenesulfonhydrazides, V-tosylaziridines ). But when the V-tosylaziridine contains an electron-withdrawing group, ring cleavage to give p-(V-tosylamino) derivatives takes precedence to detosylation. ... 

Regioselective tosylation of the primary free alcoholic function of 113, followed by reductive removal of the tosylate, Swem oxidation of secondary free alcoholic function and reductive cleavage of the ether bond of the tetrahydrofiirane ring, gave the required norbomanone 110. 

The tosyl group can be reductively removed from the 1-tosylazetidine. 

Tosylation of 754 affords tosyloxy acetal 758. Reductive removal of the tosylate furnishes a methyl derivative (91%), and subsequent hydrogenolytic cleavage of the acetal gives (R)-l,3-butanediol (759) in 87% yield [164]. 

The allylic alcohol was subjected to an Eschenmoser-Claisen rearrangement with dimethylacetamide dimethylacetal to introduce the C14 substituent in a stereoselective manner. Reduction of the amide to the corresponding aldehyde with phenyl silane in the presence of Ti(0/Pr)4 was followed by an acid-promoted closure of the C-ring of codeine. In order to prevent N-oxidation, the amine was converted to the corresponding tosylamide, via debenzylation and treatment with tosyl chloride, before the allylic alcohol was introduced by the reaction of the alkene with selenium dioxide (65). The stereochemistry of the C6 hydroxy functionality was corrected by applying the well-known oxidation/reduction protocol [46, 60] before the benzylic double bond was reductively removed under Birch conditions. Codeine (2) was obtained in 17 steps with an overall yield of approximately 0.6%. 

In order to remove the primary hydroxy group, the protected triol 24 was acet-ylated and treated with pyridinium tosylate to yield the monoester 25. Selective tosylation of the primary hydroxy group followed by Finkelstein exchange for iodine yielded the iodo derivative 26 which was transformed into the protected cyclohexene diol 27 by reductive removal of the iodine with tributyltin hydride followed by protection of the tertiary hydroxy group with dihydopyran. After removal of the benzoyl group by alkaline saponification the resulting allylic alcohol was oxidised to the desired enone 28 with pyridinium chlorochromate in buffered solution (ref. 16). 

Another convenient procedure for the reductive removal of the mesylate or tosylate group is through reaction with a Nal/Zn system The iodide intermediate which is formed in the reaction is reduced to the alkane with zinc powder. Following this procedure 2-octyl tosylate could be reduced to n-octane in high yield (equation... 

Several methods for the reduction of allylic functional groups have been reported. Although some of these are derivative of earlier procedures, useful improvements and modifications are noteworthy. For example, combination of [Pd(PhaP)4] with lithium triethylborohydride provides an effective system for the reductive removal of allylic ethers, sulphides, sulphones, selenides, and t-butyl-dimethylsilyl ethers. Many of these functional groups, of course, are not readily removed by other methods. Furthermore, this combination gives good to excellent maintenance of the regio- and stereo-integrity of the allylic double bonds. In a similar fashion, 2-tosyl homoallyl alcohols can be easily desulphonylated to... 

The synthesis of aldehyde 212 started with an Evans alkylation of the known acylated oxazolidinone 215 with allyl iodide 216 to form the corresponding alkylated product 217 as a single diastereoisomer in 81% yield (Scheme 2.88) [118]. Reductive removal of the chiral auxiliary followed by tosylation of the resulting primary alcohol, cyanide substitution, and reduction with DIBAL... 

Dialkylation of an amine or sulfonamide with a 1,3-dihalide provides a further route to azetidines <79CRV33l, 64HC( 19-2)88 5). Examples of this approach are the formation of N-tosylazetidine from tosylamide and l-bromo-3-chloropropane and the formation of N-alkylazetidinyl esters (36). The latter reaction works well except for R=Me the former provides a useful route to azetidine since the tosyl group can be removed by reductive methods. 

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