Keto mesylates

Creary, X. Carbocationic and related processes in reactions of a-keto mesylates and triflates. Acc. Chem. Res. 1985, 18, 3—8. 

Substituted oxazoline-4-carboxamides 134, present in several families of bioactive natural products, have been prepared in an efficient and general one-pot, four-component Ugi condensation of (1-keto mesylates 132, ammonia, carboxylic acids, and isonitriles, leading to intermediate diamides 133. 

Reductive Grob-like fragmentation. Reaction of the mesyloxy alcohol 1 with LiAlHi in refluxing DME gives 2 in almost quantitative yield. The corresponding keto mesylate is also converted into 2 in high yield under the same conditions. This fragmentation was used for a total synthesis of racemic -y-elemene 3. 

Geijerone (465) and y-elemene (466) have both been synthesized by reductive fragmentation of the keto-mesylate (468) which is readily available from the Wieland-Miescher ketone (467). Another synthesis of the key vemolepin... 

One-bond disconnection via Path B leads a symmetrical species of type 4. The strategy introduced in Chapter 6 suggests that making one of the carbons in the disconnected bond an electrophile (place a leaving group on the carbon), and the other a nucleophile (place a carbonyl adjacent to the carbon). After stereochemical considerations (stereoelectronic requirements of an 8 2 reaction), keto mesylate 5 can be proposed as a 1,5-difunctional intermediate that might undergo the required bond construction. 

One-bond disconnection via Path C generates bicyclo[3.3.1]nonane intermediates. Keto-mesylate 7 is a l,5-difimctional intermediate one might convert to twistane via yet a third intramolecular alkylation. This is the pathway pursued by Hamon and Young. ... 

The cyclobutanone (255) reacted with acid to furnish the keto-acid (259). Upon esterification, ketalization and reduction, (259) was converted to the alcohol (260). Mesylation of the alcohol (260) and then treatment of the mesylate with NaN3 in DMSO provided the azide (261). The azide (261) was then transformed to the urethane (262) by reduction and ethyl chloroformate reaction. The urethane (262) was deketalized by acid, nitrosated by N204—NaOAc and decomposed by NaOEt—EtOH to give the ketone (263) 89). The ketone (263) served as a starting material for the synthesis of veatchine (264)90). 

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>. 

Intramolecular cyclization of ally lie stannanes.1 The pyrrolizidine alkaloid isoretronecanol (3) can be synthesized efficiently by cyclization of the mesylate of the hydroxylactam 1 to give 2 stereoselectively. Oxidative cleavage followed by reduction of the keto group gives 3. 

In the event, iodolactonization of the carboxylate salt derived from the ester 458 afforded 459, and subsequent warming of the iodo lactone 459 with aqueous alkali generated an intermediate epoxy acid salt, which suffered sequential nucleophilic opening of the epoxide moiety followed by relactonization on treatment with methanol and boron trifluoride to deliver the methoxy lactone 460. Saponification of the lactone function in 460 followed by esterification of the resulting carboxylate salt with p-bromophenacylbromide in DMF and subsequent mesylation with methanesulfonyl chloride in pyridine provided 461. The diazoketone 462 was prepared from 461 by careful saponification of the ester moiety using powdered potassium hydroxide in THF followed by reaction with thionyl chloride and then excess diazomethane. Completion of the D ring by cyclization of 462 to the keto lactam 463 occurred spontaneously on treatment of 462 with dry hydrogen chloride. 

One remarkable process is the photochemical synthesis of 3,4-dihydro-2H-l,3-oxazin-4-ones from a-sulfonyloxy-(3-keto amides (obtained by coupling of P-keto-carboxylic acids with amines, followed by treatment with an iodanyl mesylate). This allows the regioselective oxidation of less-activated C—H bonds and a C—O bond formation which is unusual for a Norrish-Yang reaction [69]. The formation of a 1,6-0—C biradical has been postulated as an intermediate (Scheme 9.42). 

A most expeditious synthesis of triquinacene was described by Deslongchamps and his co-workers in 1973 (Scheme 58).3S°) This approach comprised degradation of Thiele s acid (363) to diketone 364 and photolysis of this intermediate to give keto aldehyde 365. Aldolization of365 led to construction of the tricyclic nucleus sequential hydride reduction, mesylation, and elimination of this intermediate over alumina efficiently provided 356. 

The hydroxy part of a hydroxy acid can also be activated for macrolactonization. Vedejs et al. [60] applied such a strategy to the synthesis of the macrocychc pyrrolizidine alkaloid monocrotaline 108). Thus, the seco acid derivative 106 was first mesylated with MsCl/EtjN in dichloromethane, and the crude product was added over 3 h to an excess of tetrabutylammonium fluoride trihydrate in acetonitrile at 34 °C to effect ring carboxy deprotection and ring closure to give 107 in 71% yield (Scheme 36). It has been noted that the active intermediate of this kind of lactonization may be an allylic chloride rather than a mesylate [61a], In addition, an intramolecular nucleophilic displacement process of chloride from an a-chloro ketone moiety by a remote carboxylate has been recently reported as an efficient approach to macrocychc keto lactones [61 bj. 

Generally, reaction with diluent and mobile phase is sometimes observed for compounds that contain keto functionalities (gem diol, oxycontin [9], active aldehyde [10], active esters such as mesyl sulfonates [11,12], and enolate intermediates [13]), so protic solvents such as aqueous/methanol should be avoided or derivatizatoin may be required either precolumn or in situ. 

This synthetic project makes provision for the regioselective oxidation of allylic hydroxyl of 13h with Jones s reactant in acetone this reaction provided the keto derivative 13i quantitatively only when we operates with small substrate quantities (few milligrams). Then the hydroxyl at C-4 has been esterified with methanesulfonyl chloride the mesylation reaction has been led in methylene chloride in presence of triethylamine at 0°C and it has brought to the formation of product 131. Then it has been substituted azide for mesyl group by the treatment of mesyl derivative 131 with sodium azide in dimethylformamide at SOX, so obtaining product 13m. 

In the other hand, although with low yields, we have succeeded in obtaining keto derivative 13i, the foUowing substitution of azido group for mesyl group brings to the predominating formation of totally unsaturated product 15, here after the elimination of an acetic add molecule (Scheme R, section B) [55],... 

The enone 3 was further functionalized via tandem reaction by Michael addition of methanol to the conjugate system at C-5, followed by base catalyzed nitromethane addition to the keto function at C-2 and base catalyzed (TMG -tetramethylguanidine) mesylation/elimination with the formation of new a-nitroenone as depicted in Scheme 7. The intermediate a-nitroenone functionalized at C-2 as a conjugate system is indeed an excellent Michael acceptor of reactive nucleophiles, including 1-thio-P-D-glucose. The conjugate addition of this reactive thiol was performed in the same fashion as before (2, 3) with the stereoselective formation of the first representative example of highly functionalized and previously unknown class of C-nitro-5-thiodisaccharide derivatives. 

Fujita and co-workers have converted the diterpenes trichokaurin (88) and enmein (89) into the keto-carboxylic acid (90), which had earlier been transformed into atisine and veatchine. The 1-mesylate of trichokaurin was oxidised to the... 

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