Enol mesylate

The copper-promoted oxidative addition process reported by Merck [183] on the vinylic bromides 321 gave rise, unexpectedly, to rearranged isopenem products, whose correct structures were independently determined at Sankyo s [184] and Schering s [117]. The S-C4 cleavage promoted by the reaction conditions was not the sole cause of insuccess, since carbacephems, but not carbapenems, could be synthesized by this route [185]. Similarly, intramolecular vinylic substitution of enol mesylate or phosphate 322a, b by the azetidinone nitrogen could not be achieved [84b]. 

Penams constitute a convenient starting material when R is methyl. Kamiya disulfides 149 were converted to the enol mesylates 150 (O3, then MsCl/TEA), which underwent chlorinolysis to generate a mixture of the required chloro-mesylates 331 and the undesired p-chloro epimers. Unfortunately, the latter prevailed (Rj = R2 = H) or were the exclusive product (R = PhCH2CONH, R2 = H), so that biologically inactive (5S)-2-methylpenems were predominantly or exclusively obtained [191, 192]. 

Though vinylic substitution of enol mesylates by external nucleophiles occurs with relative ease, this reaction could not be reproduced intramolecularly for the synthesis of penems. Attempted generation of mercaptane-mesylate 371 from benzothiazolyldithio-, acetyldithio-, and tritylthioazetidinone precursors gave only decomposition products [29b, 203]. Likewise, several attempts to achieve intramolecular Michael addition of mercaptane-butenoates (125, R = H) have been unsuccessful [204]. 

Intramolecular reactions between donor and acceptor centres in fused ring systems provide a general route to bridged polycyclic systems. The cts-decalone mesylate given below contains two d -centres adjacent to the carbonyl function and one a -centre. Treatment of this compound with base leads to reversible enolate formation, and the C-3 carbanion substitutes the mesylate on C-7 (J. Gauthier, 1967 A. Belanger, 1968). 

The Pd-catalyzed elimination of the mesylate 909 at an anomeric center, although it is a saturated pseudo-halide, under mild conditions is explained by the facile oxidative addition to the mesylate C—O bond, followed by elimination of /3-hydrogen to give the enol ether 910[767],... 

UV spectra of a variety of 1 -alkyl-1 //-1-benzazepines,20,21 3//-l-benzazepines,20 l-acyl-l//-l-benzazepines,1 3,22,23 3-acyl-3//-3-benzazepines,22-23 3-alkyl-37/-3-benzazepines and their cations in concentrated sulfuric acid,24,25 and 3-mesyl-3//-3-bcnzazepine,2ft have been recorded. A comparison of the UV spectra of 3-alkyl-l, 5-dihydroxy-3//-3-benzazepinc-2,4-dicarboxylates and their bis-O-methyl ethers supports an enol rather than an amide structure for these derivatives.14... 

The literature preparation (11) of the two-ring analog of strigol (2-RAS) involved reacting the sodium enolate (XIX) with the mesylate (XX) to form 2-RAS (XXI). In our work we found it very difficult to prepare and purify the mesylate. Low yields of 2-RAS contaminated with XVIII resulted. 

In our experience, better results were obtained using the method of Cassady and Howie (17) than by the mesylate route. Thus the sodium enolate (XIX) is reacted with the bromobutenolide (XIV) in acetonitrile to form the 2-RAS (XXI) in 50-60% crude yields which after column chromatography provided 20-30% of XXI. Similar yields were obtained when tetrahydrofuran (THF) was used as the solvent,... 

This finding is also in agreement with another three-component Michael/aldol addition reaction reported by Shibasaki and coworkers [14]. Here, as a catalyst the chiral AlLibis[(S)-binaphthoxide] complex (ALB) (2-37) was used. Such hetero-bimetallic compounds show both Bronsted basicity and Lewis acidity, and can catalyze aldol [15] and Michael/aldol [14, 16] processes. Reaction of cyclopentenone 2-29b, aldehyde 2-35, and dibenzyl methylmalonate (2-36) at r.t. in the presence of 5 mol% of 2-37 led to 3-hydroxy ketones 2-38 as a mixture of diastereomers in 84% yield. Transformation of 2-38 by a mesylation/elimination sequence afforded 2-39 with 92 % ee recrystallization gave enantiopure 2-39, which was used in the synthesis of ll-deoxy-PGFla (2-40) (Scheme 2.8). The transition states 2-41 and 2-42 illustrate the stereochemical result (Scheme 2.9). The coordination of the enone to the aluminum not only results in its activation, but also fixes its position for the Michael addition, as demonstrated in TS-2-41. It is of importance that the following aldol reaction of 2-42 is faster than a protonation of the enolate moiety. 

A new formal synthesis of ( )-zizaene (136) via the fragmentation reaction is a typical example 45,46). When the enol acetate (132) was irradiated, the isolable photoadduct (133) was formed together with other isomers. Reduction and mesylation of which afforded the mesylate (134). Then, fragmentation reaction would yield an epimeric mixture of the alkenone (755) in the presence of NaOH in aqueous dioxane at 60 °C, thus formulated a total synthesis of (+)-zizaene (136) 45-46). 

Alternatively, the triazole intermediate may be assembled via a 1,3-dipolar cycloaddition of the enol and mesyl azide ... 

A departure from the catechol pattern of the natural neurotransmitters was achieved following application of the fact that arylsulfonamido hydrogens are nearly as acidic as phenolic OH groups. Nitration of -benzyloxyacetophenone gave 18 which was reduced to 29 with Raney nickel and hydrazine, and in turn reacted with mesyl chloride to give sulfonamide 20. Methanesulfonate 20 was then transformed to soteT-enol (21), a clinically useful bronchodilator, in the... 

The synthesis of l,3-oxazin-4-ones of type 464 is the first example of the formation of a C-O bond in the course of the Norrish-Yang reaction. Upon treatment with 1-hydroxy-l-phenyl-A -iodanyl mesylate, /3-keto amide 460 was converted to the corresponding a-mesyloxy-/3-keto amide 461 in excellent yield. On ultraviolet (UV) irradiation (A>300nm) of 461, 5-hydrogen transfer to the excited carbonyl group occurred and the diradical 462 thus formed underwent MsOH elimination to enolate diradical 463, cyclization of which resulted in formation of 3-methyl-6-phenyl-3,4-dihydro-277-l,3-oxazin-4-one 464 (Scheme 89) <2001S1258>. 

The 12-step synthesis of imatinib mesylate (1) in the manufacturing process was accomplished by Novartis in an astonishingly short time. The synthesis began with a condensation reaction between 6 and ethyl formate. Deprotonation of the methyl group on 3-acetylpyndine (6) using freshly prepared sodium methoxide afforded an enolate. Condensation of the enolate with ethyl formate was followed by exchange with to produce 3-dimethylamino-l-(3-pyridyl)-2-propen-l-one (7). could be prepared from the condensation of 6 and N,N-... 

In the second step the enol ether introduced with GrignanI reagent 16 is converted into an aldehyde function. For this purpose the secondary alcohol prepared in the first step is mesylated and thus transformed into a good leaving group. 

Methyleneeyclopentane annelation (9,454-455). The mesylate (2) of 1 has been usedasan electrophilic equivalent of trimethylenemethane for methyleneeyclopentane annelation of a cyclopentanone in a synthesis of coriolin (7).2 Thus, reaction of the enolate of 4, a protected equivalent of 3, reacts with 2 to give 5, which after oxidation to the disulfone is cyclized by fluoride ion to the tricyclic methyleneeyclopentane derivative 6. The product is converted into 7 by several known transformations. 

Alternatively, diltiazem (30) has been prepared using the Evans auxiliary derivative 31 derived from L-valine (Scheme 23.7).55 After dehydration of the adduct from the condensation of 31 with anisaldehyde through the mesylate, the enol ether was formed with a Z E ratio of 4 1. This imide was then treated with 2-aminothiophenol in the presence of 0.1 equiv. 2-aminothiophenoxide with no change in the isomer ratio. The auxiliary was removed with trimethylaluminum, with concomitant formation of the lactam. After separation by crystallization, the correct diastereoisomer was converted to diltiazem in >99%ee. 

The first step is a Ferrier mercuration9 reaction on the enol ether double bond, which initiates ring-opening of the pyranoside to form 13 (Scheme 11.5). An intramolecular aldol addition reaction then ensues to give 14. After 0-mesylation, 15 undergoes an Elcb elimination reaction via enolate 16. 

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