Vinyl mesylates

Alkenylation of cyclopentenone with the alkenylstannane 719 has been used for the introduction of an a,>-chain into a prostaglandin derivative[590]. Even the vinyl mesylate (methanesulfonate) 720 can be used for coupling with alkenylstannanes[59l]. 

The is-olefin was prepared as a trans-amide bond replacement. A number of compounds incorporating substituents to mimic both natural and unnatural amino acid sidechains were prepared by adapting chemistry developed by Ibuka for the synthesis of Zs-olefin peptide isosteres (see Scheme l).40,41 The key step involved anti-SN2 displacement of vinyl mesylate 8 by boron trifluoride-activated cuprate addition. Compounds containing butyl, propyl, and benzyl substituents at the allylic positions to mimic the aj and sidechains produced potent FTase inhibitors (Table 4). 

Unlike their fully halogenated analogues, halogenated ketones and aldehydes containing one or more a-hydrogens gave the vinyl mesylate esters (equation 136) under similar reaction conditions227,223. 

Aryl and vinyl mesylate behave silimilarly [54]. The reaction has been used for the synthesis of 10,11-dihydroleukotriene B4 and related metabolites [55,56]. 

Dioxepanes 63 were hydrolyzed with aqueous hydrochloric acid to the starting diol. A thionyl chloride promoted ring-opening of dioxepane 63 to intermediate 64 has been reported. When treated with base, compound 64 can be transformed into vinylic ether 65 in 58% yield (81ZOR1047) (Scheme 31). 3-Methylfurazan-4-acetic acid was converted to the vinyl derivative 66 via an esterification, reduction, mesylation, and base elimination sequence (81JHC1247) (Scheme 31). 

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>. 

A nucleophilic attack at an allene system of the type of 417 was described for the first time by Cainelli et al. [172], namely at 444 with the chloride ion as the nucleophile (Scheme 6.91). After the treatment of the mesylate 443 with triethylamine in the presence of lithium, sodium or tetrabutylammonium chloride, mixtures of the vinyl chlorides 445 and 447 were isolated in high yields. Since the reaction did not proceed in the absence of triethylamine, the first step should be a /3-elimination of methanesulfonic acid from 443 to generate 444, which would accept a chloride ion at the central allene carbon atom. A proton transfer to either allyl terminus of the anion thus formed (446) would lead to the products 445 and 447. 

Alkenyl-1,2,5-oxadiazoles have received little attention but can be prepared by the normal substituent group manipulations thus mesylation of )5-hydroxyethylfurazans followed by treatment with DBU affords the vinyl compound <81JHC1247>. 

Metallation of 3,4-dimethyl-l,2,5-thiadiazole (55) to the anion (56) was accomplished with the use of a nonnucleophilic base, lithium diisopropylamide <82JHC1247>. Nucleophilic attack at sulfur resulted in an alkyllithium reagent <70CJC2006>. The lithiomethyl derivative (56) was carboxylated to (57) with carbon dioxide and converted to the vinyl derivative (58) via an esterification, reduction, mesylation, and base elimination sequence (Scheme 12). 

The 2-formyl-ip-methylcarbapenem 62 has been obtained in five steps from a readily available P-lactam in 23-26% overall yield <98MI1294>. Suzuki-Miyaura cross-coupling of aiylboronic acids and vinyl triflates is a convenient route to 2-aiylcarbapenems on a small scale but may present problems on a large scale. Vinyl phosphates, mesylates or tosylates are convenient alternatives to triflates <9981471>. Radical cyclizations of readily available enyne-2-azetidinones (e.g., 63) with a tin hydride, RjSnH, provides a route to the... 

Addition to allylic mesylates.6 Conjugate addition of organocyanocuprates to acyclic allylic mesylates substituted at the P-position with a chiral sulfoxide group involves an SN2 -substitution with high Z/E stereoselectivity and high asymmetric induction. This reaction provides a route to chiral trisubstituted vinyl sulfoxides. 

ICD mediated the addition of aryl methylbenzenesulfonamides, such as 105, to ethyl or methyl vinyl ketones in MeCN DMF (1 1) mixtures at a lower temperature (—30 °C) [95a]. The reaction afforded products with (R) absolute configuration (Table 5.13). Of note, this situation was opposite to that observed in the related aza-MBH reaction with acrylonitrile with acryl aldehyde or with acrylates. Related N-mesyl or N-SES-protected imine afforded similar results. 

Treatment of 2-azido-3-hydroxy-l,4-diones 68 with mesyl chloride in the presence of base affords 5-substituted 3-acylisoxazoles 71, probably through vinyl azide 69 and nitrene 70 intermediates (Scheme 42) <2002EJ03055>. In a similar way, thermolysis of 3-azido-2-halopropenones gave 4-haloisoxazoles in high yields <2002S605, CHEC-III (4.03.9.1.3)426>. 

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