Ketones 3-butenylation

The distinction between Pd and Rh catalysts was also verified for diazoketone 190. In this case, the carbonyl ylide was trapped by intramolecular [3+2] cycloaddition to the C=C bond195. Decomposition of bis-diazoketone 191 in the presence of CuCl P(OEt)3 or Rh2(OAc)4 led to the pentacyclic ketone 192 most remarkably, one diazoketone unit reacted by cyclopropanation, the second one by carbonyl ylide formation 194). With [(r 3-C3H5)PdCl]2, a non-separable mixture containing mostly polymers was obtained, although bis-diazoketones with one or two allyl side chains instead of the butenyl groups underwent successful twofold cyclopropanation 196). 

These transformations were applied to develop a new promising method for synthesis of various bridged polycyclic systems66, viz. ketones 160 and 161. Tropone reacts with butenyl magnesium bromide (—78 °C, 75%) to form a mixture of 2-(3-butenyl)dihydrotropones 158 and 159, the pyrolysis of which (200-210 °C, neat or in heptane solution) leads to 60% total yield of the isomeric homoprotoadamantenones 160 and 161 and the tricyclic ketone 162 in a ratio of 58 18 24, respectively (equation 49)66. 

Catalytic asymmetric methylation of 6,7-dichloro-5-methoxy-2-phenyl-l-indanone with methyl chloride in 50% sodium hydroxide/toluene using M-(p-trifluoro-methylbenzyDcinchoninium bromide as chiral phase transfer catalyst produces (S)-(+)-6,7-dichloro-5-methoxy-2-methyl-2--phenyl-l-indanone in 94% ee and 95% yield. Under similar conditions, via an asymmetric modification of the Robinson annulation enqploying 1,3-dichloro-2-butene (Wichterle reagent) as a methyl vinyl ketone surrogate, 6,7 dichloro-5-methoxy 2-propyl-l-indanone is alkylated to (S)-(+)-6,7-dichloro-2-(3-chloro-2-butenyl)-2,3 dihydroxy-5-methoxy-2-propyl-l-inden-l-one in 92% ee and 99% yield. Kinetic and mechanistic studies provide evidence for an intermediate dimeric catalyst species and subsequent formation of a tight ion pair between catalyst and substrate. 

The stereoselectivity of addition to aldehydes and ketones has been of considerable interest.111 112 With benzaldehyde, the addition of 2-butenylstannanes catalyzed by BF3 gives the syn isomer, irrespective of the stereochemistry of the butenyl group.113... 

The Dauben-Walker approach has yielded the smallest and most strained fenestrane known to date Following the intramolecular Wadsworth-Enunons cyclization of 443 which also epimerizes the butenyl sidechain to the more stable exo configuration, intramolecular photocycloaddition was smoothly accomplished to provide 444. Wolff-ELishner reduction of this ketone afforded the Cj-symmetric hydrocarbon 445. Application of the photochemical Wolff rearrangement to a-diazo ketone 446 p,ve 447. 

An intramolecular cycloaddition of the tetradecatrienyl nitroethyl ether 263 was used in the synthesis of the 14-membered bicyclic precursor 265 of crassin acetate 266, a cembrane lactone possessing antibiotic and antineoplastic activity (332). Nitro compound 263 was obtained from farnesyl acetate (262) in several steps and was then treated with phenyl isocyanate and triethylamine to give the tricyclic isoxazoline 264 (Scheme 6.98). Conversion to ketone 265 was accomplished by hydrogenation of the cycloadduct with Raney Ni and boric acid followed by acetylation (332). In this case, the isoxazoline derived from a 3-butenyl nitroethyl ether moiety served to produce a 3-methylenetetrahydropyran moiety (332). 

For the general condensation reaction of secondary amines with ketones to yield enamines, pyrrolidine, piperidine, or morpholine is generally used. The rate of enamine formation depends on the basicity of the secondary amine and the steric environment of the carbonyl group [12a, b, 29], Pyrrolidine, which is more basic, usually reacts faster than morpholine. The investigation of piperazine, a disecondary amine, has only been reported recently by Benzing [45, 46] and Sandler [41]. Surprisingly, the reaction of excess -butyraldehyde with piperazine in tetrahydrofuran at — 20°C to 0°C gave mainly AM-butenyl-piperazine [41] (see Eq. 13). 

One approach to tetrahydropyridinones is the Lewis acid mediated hetero-Diels-Alder reaction of electron-rich dienes with polystyrene-bound imines (Entries 3 and 4, Table 15.23). The Ugi reaction of 5-oxo carboxylic acids and primary amines with support-bound isonitriles has been used to prepare piperidinones on insoluble supports (Entry 5, Table 15.23). Entry 6 in Table 15.23 is an example of the preparation of a 4-piperidinone by amine-induced 3-elimination of a resin-bound sulfinate followed by Michael addition of the amine to the newly generated divinyl ketone. The intramolecular Pauson-Khand reaction of propargyl(3-butenyl)amines, which yields cyclopenta[c]pyridin-6-ones, is depicted in Table 12.4. 

In fact, the role of copper and oxygen in the Wacker Process is certainly more complicated than indicated in equations (151) and (152) and in Scheme 10, and could be similar to that previously discussed for the rhodium/copper-catalyzed ketonization of terminal alkenes. Hosokawa and coworkers have recently studied the Wacker-type asymmetric intramolecular oxidative cyclization of irons-2-(2-butenyl)phenol (132) by 02 in the presence of (+)-(3,2,10-i -pinene)palladium(II) acetate (133) and Cu(OAc)2 (equation 156).413 It has been shown that the chiral pinanyl ligand is retained by palladium throughout the reaction, and therefore it is suggested that the active catalyst consists of copper and palladium linked by an acetate bridge. The role of copper would be to act as an oxygen carrier capable of rapidly reoxidizing palladium hydride into a hydroperoxide species (equation 157).413 Such a process is also likely to occur in the palladium-catalyzed acetoxylation of alkenes (see Section 61.3.4.3). 

The 1,5-diketone 26 is prepared by 3-butenylation of ketone, followed by the Pd-catalyzed oxidation of 25 and annulated to form cyclohexenone 27 [18]. In this method, the 3-butenyl group is the masked methyl vinyl ketone. The 3-butenyl group attached to the B ring of the baccatin skeleton 28 was oxidized to the methyl ketone 29 in 98% yield, whereas the corresponding allyl group was oxidized to aldehyde [35]. 

Allyl -phenylvinyl ether 4 <175 — 7-Butenyl phenyl ketone 71% 10... 

Acyldihydrocodeinones (146) were made in a similar manner. The 8/3-(trans-1 -oxo-2-butenyl)- and 8/3-benzoyl derivatives were prepared from protected acyl lithium cuprates, and the 8/3-methylcarbonyl- (146) from the lithium bis(a-ethoxyvinyl) cuprate with codeinone, followed by mild hydrolysis of the intermediate, 147. Preparation of 8/3-t-alcohols may be achieved from 147 after reduction of the ring carbonyl, treatment with an appropriate alkyl lithium to 148, and oxidation back to a ketone, 149. 

Dicarbonyl compounds can be prepared by the reactitHi of kemnes with 3-butenyl halide as a Q component, following oxidation of the terminal double bond. A modified method for 3-butenylation of ketones by the palladium-catalyzed reaction of 4-acetoxy-2-butenylmethyl carbonate with ketones, followed by the palladium-catalyzed reaction of ammoiuum formate was reported (Scheme 15). ... 

In this synthesis of 1,5-dicaibonyl compounds, 3-butenyl halide is behaving as a madced 3-oxobutyl reagent, and can be used as an equivalent of metiiyl vinyl ketone. These reactirais offer new anellation methods. Also 1,4-addition of the allyl group to enones, followed by oxidatitm. offers a conveiuent synthetic method for 1,5-diketone preparation. Lewis acid promoted Nfichael addition of allylsilane (48) to a,p-unsaturated ketones, followed by the palladium-catalyzed oxidation, affods 1,5-diketones (Scheme 17). 3... 

In the simplest example, Michael addition to the enone (67) of the cyclohexanone enamine and aldol condensation yielded 4-(3-butenyl)-3-oxo-A -octalin (69). Tbe terminal double bond was oxidized to the ketone (70) by PdCli/CuCl/Oz, and subsequent aldol condensation leads to the tricyclic ketone (71 Scheme 21 ... 

Methyl-2-eyclopentenones. Enol silyl ethers of 3-butenyl methyl ketones such as 1 and 3 are cyclized exclusively to 2-cyclopentenones (2,4) in the presence of palladium(II) acetate (1 equiv.) at room temperature with deposition of Pd(0). 

Keton + Cl — COOallyl) 6-Allyl-2-methyl-l-oxo- E18, 1048 (Keton + Cl-COOallyl) (Allyloxy-methylen)- E1S/1, 168 ( -CHN2 + Keton/R-OH) ( /Z)-2-(2-Butenyl)-l-oxo- E18, 1062 (Decarboxylier.)... 

Acetoxy-f)WM-5-methyl-4-(3-methyl-2-butenyl)-3-oxo- E15/1, 78 (Keton + R-COOH)... 

The more sterically demanding (7) -2-butenyl)Fp cycloadds to diethyl methylenemalonate to give adduct (8) as a mixture of stereoisomers (equation 5). In this case the poor stereoselectivity may be due to the fact that the starting butenyl complex is a mixture of cis and trans isomers. Formation of the bicyclic ketone (9) ftom the reaction of (Tri -2-methallyl)Fp and 2-ethoxycarbonylcyclopentenone suggests that alkyl substituents can also be tolerated at C-2 of the (allyl)Fp unit (equation 6). The corresponding (t) -2-methoxyallyl)Fp fails to produce any cycloadduct with 2-ethoxycarbonylcyclohexenone or 2-cyclo-... 

For instance, that an isomerization followed by decarboxylation is the most probable process involved in the transformation of keto ester XIX into ketone XX is suggested, on the one hand, by the fact that the four-carbon chain of the butenyl ester is present in the product ketone on the same position occupied by the carboxylate unit in XIX. On the other hand, the empirical formulas indicate the departure of one carbon and two oxygen atoms, in ail probability belonging to carbon dioxide. 

Gomtsyan, A. Org. Lett. 2000, 2, 11. For a reaction with methyl esters with an excess of vinylmagnesium halide and a copper catalyst to give a 3-butenyl ketone by a similar acyl substitution-Michael addition route, see Hansford, K.A. Dettwiler, J.E. Lubell, W.D. Org. Lett. 2003, 5, 4887. Gomtsyan, A. Koenig, R.J. Lee, C.-H. J. Org. Chem. 2001, 66, 3613. 

Tsuji, J., Shimizu, I., Yamamoto, K. Convenient general synthetic method for 1,4- and 1,5-diketones by palladium catalyzed oxidation of a-allyl and a-3-butenyl ketones. Tetrahedron Lett. 1976, 2975-2976. 

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