Ketones, methyl vinyl reduction

Other limitations of the reaction are related to the regioselectivity of the aryl radical addition to double bond, which is mainly determined by steric and radical delocalization effects. Thus, methyl vinyl ketone gives the best results, and lower yields are observed when bulky substituents are present in the e-position of the alkene. However, the method represents complete positional selectivity because only the g-adduct radicals give reductive arylation products whereas the a-adduct radicals add to diazonium salts, because of the different nucleophilic character of the alkyl radical adduct. ... 

Reactions of 3- and 4-piperidone-derived enamines with a dienester gave intermediates which could be dehydrogenated to tetrahydroquinolines and tetrahydroisoquinolines (678). The methyl vinyl ketone annelation of pyrrolines was extended to an erythrinan synthesis (679). Perhydrophenan-threnones were obtained from 1-acetylcyclohexene and pyrrolidinocyclo-hexene (680) or alternatively from Birch reduction and cyclization of a 2-pyridyl ethyl ketone intermediate, which was formed by alkylation of an enamine with a 2-vinylpyridine (681). 

Electrochemical reduction of oxazolinium salts 36 gives the anions 37, which add efficiently to alkyl halides or, in the presence of McsSiCl, to methyl acrylate, methyl vinyl ketone, and acrylonitrile. Simple acid hydrolysis then gives the ketone products 38 and 39, and this method is quite general since the starting salts are readily prepared from carboxylic acids, R C02H (87TL4411). 

The Michael addition of cyclic a-nitro ketones to acrolein or methyl vinyl ketone followed by reduction of the carbonyl group and treatment with base results in the ring expansion (Eq. 

Hesse and coworkers have used this strategy for the preparation of various macrolides.173 For example, Michael addition of 2-nitrocyclodecanone methyl vinyl ketone followed by reduction with (5)-alpine-hydride gives the nitrolactone in 72% yield. Radical denitration of the nitrolactone with Bu3SnH gives (+)-(5)-tetradecan-13-olide in 44% yield (Eq... 

The Michael reaction of nitromethane with methyl vinyl ketone and l-decene-3-one followed by reductive cyclization gives two isomeric pyrrolizidines, depending on reduction conditions (Eq. 10.74).117... 

Scheme 22.8 Use of methyl vinyl ketone (MVK) in intermolecular hydrogen-mediated reductive aldol coupling.a)...

As in the reductive ring-opening, titanocene—oxygen bonds have to be protonated. Here, a titanium enolate, which is generated after reductive trapping of an enol radical, has to be protonated, in addition to a simple titanocene alkoxide. As before, 2,4,6-collidine hydrochloride constitutes a suitable acid to achieve catalytic turnover, but here zinc dust turned out to be the reductant of choice [31c], The features of the stoichiometric reaction are preserved under our conditions. Acrylates and acrylonitriles are excellent radical acceptors in these reactions. Methyl vinyl ketone did not yield the desired addition product. Under the standard reaction conditions, a-substituted acceptors are readily tolerated, but (3-substitution gives the products only in low yields. 

Simple synthesis of ( )-17-epiyohimbol (73) has been reported by Mori et al. (214). yV-Benzyloctahydroindolo[2,3-a]quinolizinone (126), prepared according to the procedure of Novdk and Szdntay (97) was coverted to the corresponding pyrrolidine enamine, which was treated with methyl vinyl ketone to give N-benzylyohimbenone (379). Reduction of 379 with sodium in liquid ammonia... 

Mesityl oxide at a mercury cathode in acetate buffer affords a mixture of tail-to-tail and head-to-tail hydrodimers. The initally formed reduction products undergo further reactions so that 32 and 33 are isolated [106, 107, 108]. A low yield of the head-to-head glycol has been isolated from some reactions [109, 110, 111]. The structures of these products were confirmed in 1955 [112], Methyl vinyl ketone yields a mixture of tail-to-tail and head-to-head hydrodimers [113],... 

Some intramolecular aminations of olefins have been reported for solenopsin A (Id) and its isomer (Ic) (389-392). The dimer (200) of methyl vinyl ketone was converted to the ketone (202) by a standard procedure. Borohydride reduction of 202, followed by acid-catalyzed cyclization, yielded an exo/endo (60/40)... 

Condensation (FeCl, ZnClj, HCl) of these amine salts with methyl vinyl ketone produced 4-methylthleno[2,3-/>]thieno[2,3-h]pyridine and 4-methylthieno[3,2-6]thieno[2,3-6]pyridine, respectively , while acetylacetone (ZnClj) afforded the 2,4-dimethyl derivatives. 5-Ethyl-2-formylthieno[2,3-Z>]thiophene (211) and nitromethane by the Knoevenagel method gave 2-/3-nitrovinyI-5-ethylthienol2,3-6]-thiophene (212) (73%) reduction (LAH) of 212 led to the 2-/3-amino-ethyl analog (213) lEq. (69)]. 

Scheme 1.64). The Ag(I)-mediated cyclization afforded dipole 306 for 1,3-dipolar cycloaddition with methyl vinyl ketone to yield adducts 307 and the C(2) epimer as a 1 1 mixture (48%). Hydrogenolytic N—O cleavage and simultaneous intramolecular reductive amination of the pendant ketone of the former dipolarophile afforded a mixture of alcohol 308 and the C(6) epimer. Oxidation to a single ketone was followed by carbonyl removal by conversion to the dithiolane and desulfurization with Raney nickel to afford the target compound 305 (299). By this methodology, a seven-membered nitrone (309) was prepared for a dipolar cycloaddition reaction with Al-methyl maleimide or styrene (301). 

In the case of the electron poor alkenes, results were more varied. Under all conditions examined, reactions with methyl vinyl ketone, acrylonitrile, methacrylonitrile and 4-vinyl pyridine afforded products with IR spectra equivalent to those obtained without the addition of the alkene (side reaction). In the cases of vinyl bromide and chloromethyl styrene, unreacted PCTFE was recovered unchanged. It is speculated that electron transfer to the alkene proceeded in each case. While the product of vinyl bromide reduction was not observed, perhaps because of volatility, one could isolate poly(chloromethylstyrene) in the latter case. 

Organometallics are formed at the cathode if transient radicals produced in reductions react with the active electrode. This occurs as a side reaction in cathodic coupling (Sect. 12.2, Eq. (185)) of carbonyl compounds, e.g., of acetone 3 9 or of activated olefins, e.g., of methyl vinyl ketone 41or acrylonitrile. Furthermore, in cathodic cleavage (Sect. 13.2, Eq. (227) ) of alkyl bromides or iodides organometallics are formed, e.g., ME(CH2CH2CN)2(ME = Pb, Tl, Sn, Hg) 481 bis(p-substituted benzyl)mercury 485 or dicyclopropylmercury 489 ... 

In a more recent study Co(dppe)I2 was used as a catalyst for reductive additions of primary, secondary, and tertiary alkyl bromides or iodides 249 to alkyl acrylates, acrylonitrile, methyl vinyl ketone, or vinylsulfone 248 in an acetonitrile/water mixture using zinc as a stoichiometric reducing agent [305]. The yields of the resulting esters 252 were mostly good. The authors tested radical probes, such as cyclopropylmethyl bromide or 6-bromo-1-hexene (cf. Part 1, Fig. 8). However, the latter did not cyclize, but isomerized during addition, while the former afforded complicated mixtures. On this basis the authors proposed a traditional two-electron mechanism to be operative the results do not, however, exclude a radical-based Co(I) catalytic cycle convincingly (Fig. 61). 

The starting material for the present synthesis was Wieland-Miescher ketone (24), which was converted to the known alcohol (25) by the published procedure [10], Tetrahydropyranylation of alcohol (25) followed by hydroboration-oxidation afforded the alcohol (26), which on oxidation produced ketone (27). Reduction of (27) with metal hydride gave the alcohol (28) (56%). This in cyclohexane solution on irradiation with lead tetraacetate and iodine produced the cyclic ether that was oxidized to obtain the keto-ether (29). Subjection of the keto-ether (29) to three sequential reactions (formylation, Michael addition with methyl vinyl ketone and intramolecular aldol condensation) provided tricyclic ether (30) whose NMR spectrum showed it to be a mixture of C-10 epimers. The completion of the synthesis of pisiferic acid (1) did not require the separation of epimers and thus the tricyclic ether (30) was used for the next step. The conversion of (30) to tricyclic phenol (31) was... 

Reduction of 2,2-dimethyl-cyclohexane-1,3-dione (50) with Baker s yeast gave alcohol (ee 98.3%) whose tetrahydropyranyl derivative on methoxycarbonylation produced (51) quantitatively. Michael addition of (51) with methyl vinyl ketone followed by heating the adduct under reflux with pyrrolidine in benzene yielded (52) in 85% yield as stereoisomeric mixture whose separation presented problems. In order to eliminate the complexity due to a chiral center in tetrahydropyranyl protective group, deprotection of (52) was achieved by treatment with p-toluenesulphonic acid in methanol. The product obtained was a mixture of the lactone (53) and hydroxy ester (54). Probably the stereoisomer of... 

---