Selective mesylation

N-Mesylation. Selective mesylation with 1 in DMF at room temperature has been demonstrated. A primary amino group undergoes mesylation in preference to a secondary amine. Only Al-mesylation of amino alcohols with this reagent is achieved. 

The apphcation of bimolecular, nucleophilic substitution (S ) reactions to sucrose sulfonates has led to a number of deoxhalogeno derivatives. Selective displacement reactions of tosyl (79,85), mesyl (86), and tripsyl (84,87) derivatives of sucrose with different nucleophiles have been reported. The order of reactivity of the sulfonate groups in sucrose toward reaction has been found to be 6 > 6 > 4 > 1. ... 

The use of potassium hydrogen carbonate for the cyclization of thiocyan-atohydrin mesylates containing alkali-sensitive groups has been reported, but the selectivity for thiirane formation is reduced. ... 

The syntheses were effected by selective mesylation of one or two hydroxyl groups and displacement of each mesyloxy group by an azido group, which was reduced to amino. Although attempted SN2 displacement of cyclohexane substituents is often unsuccessful, the powerfully nucleophilic azide ion is usually able to displace an alkylsulfonoxy group, and this route has been exploited in several recent cyclitol syntheses. 

In view of the unexpected effects of the C-2 and C-3 substituents on the reaction of C-4 sulfonates, it is worthwhile to point out the observations made with some 2,3-dideoxy derivatives. Treatment of ethyl 2,3-dideoxy-4,6-di-0-methylsulfonyl-D-ert/ hro-hexopyranoside (40) with sodium iodide and acetone at 115°C. caused the displacement of the C-6 mesylate group selectively to give 41. Catalytic hydrogenation then gave the corresponding ethyl 4-0-methylsulfonyl-2,3,6-trideoxy- -D-en/ /iro-hexoside in good overall yield (83%) (72). 

Hydrogenolysis of the C-7 benzyl ether, followed sequentially by selective triethylsilylation of the newly liberated C-7 hydroxyl and mesylation of the C-5 secondary hydroxyl, provides compound 34 in 60% overall yield (see 33—>34, Scheme 6). On the basis of Potier s studies,35 it was hoped that the C 20 hydroxyl group,... 

Deoxy-3 -fluorothymidine (813), a selective inhibitor of DNA synthesis, was prepared " in moderate yields from 3 -0-mesyl- or 3, 5 -di-O-mesyl-thymidine, through 2,3 -anhydro-1 -(2-deoxy- -D-t/2reopentofur-anosyl)thymine (808), by treatment with hydrogen fluoride (0.1% HF in l,4-dioxane-AlF3, 3.764 hf in DMF-AlFj, or 10% HF in DMF ),... 

The objective in selecting the reaction conditions for a preparative nucleophilic substitution is to enhance the mutual reactivity of the leaving group and nucleophile so that the desired substitution occurs at a convenient rate and with minimal competition from other possible reactions. The generalized order of leaving-group reactivity RSOj" I- > BF > CF pertains for most Sw2 processes. (See Section 4.2.3 of Part A for more complete data.) Mesylates, tosylates, iodides, and bromides are all widely used in synthesis. Chlorides usually react rather slowly, except in especially reactive systems, such as allyl and benzyl. 

Reduction of ketone 85 with NaBkLt in THF formed the a-alcohol selectively (98, >23 1 dr, 55 % yield) which was then protected as the mesylate... 

R2Cu(CN)Li2 reaction with vie-epoxy mesylatesA higher-order cuprate reacts selectively with the epoxide group of the epoxy mesylate 1 to provide 2 with inversion at C3. Ring closure of 2 furnishes the epoxide 3, which reacts with a second equivalent of the higher-order cuprate to furnish meso-4, with inversion at both C, and C3. This two-step reaction provides a route to acyclic alcohols with useful stereocontrol at both adjacent centers. 

D-Ribonolactone is a convenient source of chiral cyclopentenones, acyclic structures, and oxacyclic systems, useful intermediates for the synthesis of biologically important molecules. Cyclopentenones derived from ribono-lactone have been employed for the synthesis of prostanoids and carbocyclic nucleosides. The cyclopentenone 280 was synthesized (265) from 2,3-0-cyclohexylidene-D-ribono-1,4-lactone (16b) by a threestep synthesis that involves successive periodate oxidation, glycosylation of the lactol with 2-propanol to give 279, and treatment of 279 with lithium dimethyl methyl-phosphonate. The enantiomer of 280 was prepared from D-mannose by converting it to the corresponding lactone, which was selectively protected at HO-2, HO-3 by acetalization. Likewise, the isopropylidene derivative 282 was obtained (266) via the intermediate unsaturated lactone 281, prepared from 16a. Reduction of 281 with di-tert-butoxy lithium aluminum hydride, followed by mesylation, gave 282. 

Due to its reliability, the SN2 substitution is often used in applications which require the highly enantioselective formation of the allene for example, Brummond et al. [19g] prepared the yneallene 19 (a starting material for intramolecular allenic Pauson-Khand cycloadditions) through the anti-selective SN2 substitution of the chiral propargylic mesylate 18 with a suitable magnesium cuprate (Scheme 2.6). 

Reductions of propargyl bromides, mesylates and phosphates using LiAlH4, NaBH4 and LiBHEt3 as reductants were reported however, the selectivity towards allenic products was generally low [49, 50],... 

The application of this method to trifluoromethyl analogues has been reported [116]. Trifluoromethylpropargylic mesylates undergo highly selective conversion to allenylzinc reagents, which add in situ to aldehydes producing the expected anti homopropargyl alcohols (Eqs. 9.136 and 9.137). 

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