Ethyl mesyl derivative

Pankova and Tichy prepared all four stereoisomeric 4-rerr-butyl-2-aminomethyl-l-cyclohexanols and cyclized them with ethyl benzimidate to hexahydro-l,3-benzoxazines 158-161 (74CCC1447). From the A-acyl O-mesylate derivatives 162 and 163 on thermal cyclization or thionyl chloride treatment, ring closure occurred with inversion and resulted in 158 and 159 (74CCC1447). 

S)-( — )-Methyloxirane (40) is available in multigram quantities from L-ethyl lactate by initial reduction of the ester to ( S)-( + )-propane-l,2-diol (36). Conversion of the primary alcohol to a suitable leaving group provides intermediates 38 or 39, which afford the epoxide (96% ee) upon treatment with base [14,15] (Scheme 5). Oxirane 40 is also accessible from O-EE-protected ethyl lactate (see Section 1.4.4). (i )-( + )-methyloxirane can be similarly synthesized from L-ethyl lactate via its O-tosyl (Section 1.2.2.1) or 0-mesyl derivative (Section 1.2.2.2). 

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). 

The reaction of 5-[2-(iV,./V-dimethylamino)ethyl]-l,2,4-oxadiazole with methyl iodide forms the quaternary ammonium salt 170 (Scheme 22), which undergoes elimination in the presence of base (diisopropylethylamine (DIEA), TEA, l,8-diazabicyclo[4.3.0]undec-7-ene, etc.) to form an intermediate 5-vinyl-l,2,4-oxadiazole 171, which undergoes in situ Michael addition with nucleophiles to furnish the Michael adducts 172. As an example, also shown in Scheme 22, 3-hydroxy-pyrrolidine allows the synthesis of compound 172a in 97% yield. Mesylation followed by deprotonation of the 1,2,4-oxadiazole methylene at C-5 enables Sn2 displacement of the mesylate to give the 5-azabicycloheptyl derivative 173, which is a potent muscarinic agonist <1996JOC3228>. 

Figure 4.10 Selected ion-monitoring chromatograms of the thiocyanate and isothiocyanate derivatives of methyl, ethyl and isopropyl mesylates (final concentrations 0.25 pg/ml). Reproduced from [60] by permission of the Royal Society of Chemistry.

An efficient synthesis of ( )-quebrachamine is based on the construction of a suitable precursor via ring cleavage of an a-diketone monothioketal (810) (80JCS(P1)457). This monothioketal, available from 4-ethoxycarbonylcyclohexanone ethylene ketal, was fragmented to the dithianyl half ester (811) with sodium hydride in the presence of water. Reaction of (811) with tryptamine and DCC provided an amide which was converted to the stereoisomeric lactams (812) on hydrolysis of the dithiane function. Reduction of either the a- or /3-ethyl isomer with lithium aluminum hydride followed by conversion of the derived amino alcohol to its mesylate produced the amorphous quaternary salt (813). On reduction with sodium in liquid ammonia, the isomeric salts provided ( )-quebrachamine (814 Scheme 190). 

The 4,6-anhydro derivative 93 has been reportedly prepared from ethyl 2,3-dideoxy-o -D-t/zreo-hex-2-enopyranoside by mesylation at C-6 to give 92 and action of base 354 in a similar way a 4,6-anhydro-a-D-galactopyranosyl component was built into a nonreducing disaccharide.355... 

At about the same time, a synthesis of leukotriene-A, also termed SRS-A ( slow reacting substance of anaphylaxis ), which made use of the Wittig olefmation was described77). The ylide of 100 is reacted with ethyl 5-formyl-2,4-pentadienoate 101 to give the ( , , Z, Z)- tetraenoic ester 102. Reduction and mesylation of 102, subsequent conversion into the sulfonium salt, and treatment of the latter with a base yields a sulfonium ylide which is reacted with methyl 4-formylbutanoate 69 to the epoxy-tetraenoic ester 103. After separation of the cis-epoxide by HPLC, 103 was treated with the S-trimethylsilyl derivative of glutathione dimethyl ester N-trifluoroacet-amide. The diastereomeric products thus obtained were separated by means of HPLC and hydrolyzed to 104 77) (Scheme 18). 

Dihydroxylation of the stilbene double bond in the trans isomers of Combretastatin A-1 and A-4 produced diols which by treatment with boron trifluoride in ethyl ether [44] or with trifluoroacetic acid [17] resulted in pinacolic rearrangement to produce an aldehyde. The aldehyde was converted in a variety of derivatives, as illustrated in the Scheme 20, via the following reaction sequence reduction with sodium borohydride to primary alcohol which was derivatized to the corresponding mesylate or tosylate, substitution with sodium azide and final reduction to amine with lithium aluminum hydride. Alternatively the aldehyde was converted to oxime which was catalitically hydrogenated to amine [17]. 

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