A-Methylene esters

Dipolar cycloadditions of ( -phenyl-/V-methylnitrone (585) to Baylis-Hillman adducts such as ( 3-hydroxy-a-methylene esters) (608-610) proceed with complete regioselectivity in good yields to afford the corresponding diastere-omeric 3,5,5-trisubstituted isoxazolines (611-613) (Scheme 2.269). Attack by the dipole in (585) from the less sterically hindered side of dipolarophiles (608-610) affords C-3/C-5 cis isoxazolidines (611a,b-613a,b) as the major products (780). 

Aggarwal and coworkers have studied the electrophilic behavior of enantiomerically pure N-p-toluenesulfinimines and N-tert-butanesulfinimines in the asymmetric Baylis-Hillman reaction with methyl acrylate with and without Lewis acids [26], In the presence of In(OTf)3 good yields and high diastereoselectivities have been achieved providing an effective route to /i-amino-a-methylene esters. 

Radical-mediated reaction of 7-hydroxy or 7-alkoxy-a-methylene ester (21) with iso-Prl in the presence of MgBr2 gives the yyrc-adduct (22a) predominantly via the intermediate [V] as shown in eq. 10.11. The same chelation-controlled radical 1,3-stereo... 

The same method can he used to convert a-nitro esters into a-methylene esters, except that the hydroxymethylation step is catalyzed with sodium hydroxide rather than triphen-ylphosphine. 

The cyclocondensation of 1,2-diketones, reactive a-methylene esters and hydrazines leads, in its simplest form as a one-pot reaction, to pyridazin-3(2//)-ones 11 (Schmidt-Druey synthesis) ... 

In another study, Eisera et al. studied the same nitrone, 130, in 1,3-dipolar cycloadditions to j8-hydroxy-a-methylene esters 150 under thermal heating or microwave... 

A -aIlyl- 3-amino-a-methylene esters were produced in good yields and enantiose-lectivities using 20 mol% of commercially available quinidine (Scheme 11.39). Further potential of the method could be inferred from the ring-closing metathesis (RCM) of adducts, using Zhan 1-B catalyst (5 mol%), to yield enantioenriched 2,5-dihydropyrroles without loss of optical purity. 

The crade rearrangement product was directly subjected to elimination giving rise to the a-methylene ester 211. Although a number of steps are involved in the transformation 213 214, the entire operation may be conducted in a single flask. 

The homolog methyl 2-chloro-2-phenylthiopropanoate (7) can be used in similar reactions (eqs 7-9), but the oxidative desulfurization takes place towards the methyl group, giving the a-methylene ester (8) when R is not hydrogen (eq 9). ... 

A number of new routes to a-methylene esters (121) have been developed (see also ref. 110). Perhaps the simplest involves the treatment of malonic acid half-esters with formaldehyde in pyridine containing piperidine. Yields are ca. 80%. A somewhat less efficient scheme utilizes a reaction between silyl keten acetals and chloromethyl methyl ether followed by pyrolytic removal of methanol (160 °C, KHS04). Esters (121) can also be obtained in 31—83% yield by alkylation of the Diels-Alder adduct of dimethylfulvene and methyl acrylate followed by a retro-Diels-Alder reaction. " ... 

The Bayliss-Hillman reaction is commonly used for the coupling of Michael acceptors with aldehydes to give /3-hydroxy-a-methylene esters/ketones/nitriles. The use of imines in place of aldehydes provides entry to the corresponding /3-amino products. Examples of the asymmetric Bayliss-Hillman reaction with imines are very rare. Aggarwal and co-workers have shown that indium(III) triflate in combination with 3-hydroxyquinuclidine (3-HQD) catalyzes the reaction of enantiomerically pure N-p-toluenesulfinimine with methyl acrylate in an asymmetric Bayliss-Hillman reaction (eq 15). Higher diastereoselectivity was observed in the reaction of A-tert-butanesulfinimines, however, the yields were much poorer. ... 

The acylpalladium complex formed from acyl halides undergoes intramolecular alkene insertion. 2,5-Hexadienoyl chloride (894) is converted into phenol in its attempted Rosenmund reduction[759]. The reaction is explained by the oxidative addition, intramolecular alkene insertion to generate 895, and / -elimination. Chloroformate will be a useful compound for the preparation of a, /3-unsaturated esters if its oxidative addition and alkene insertion are possible. An intramolecular version is known, namely homoallylic chloroformates are converted into a-methylene-7-butyrolactones in moderate yields[760]. As another example, the homoallylic chloroformamide 896 is converted into the q-methylene- -butyrolactams 897 and 898[761]. An intermolecular version of alkene insertion into acyl chlorides is known only with bridgehead acid chlorides. Adamantanecarbonyl chloride (899) reacts with acrylonitrile to give the unsaturated ketone 900[762],... 

KNOEVENAGEL OOEBNER STOBBE Condensation Base catalyzed aldol condensation of aldehydes or ketones with an activated methylene group of a malonic ester (Knoevenagel Doebner) or a succinic ester (Stobbe)... 

Androst-4-ene-3,l 1,17-trionehas been converted into several 3,17-dienamine derivatives which, on reduction with LiAlH4 followed by removal of the protecting groups, give 11 jS-hydroxyandrost-4-ene-3,17-dione. An unsaturated 3-ketone has also been protected as an enamine in the LiAlH4 reduction of a 21-ester group a further example is the conversion of 7-methylene-5a-an-drostane-3,17-dione into the 3-pyrrolidine enamine followed by reduction of the 17-ketone by Li[OC(CH3)3]3 AlH. ... 

Condensation between carboxylic esters and aldehydes or ketones Addition of a-metalated esters to ketones Oxidation of methylene to OH, O2CR, or OR... 

C20H29O2 54024-7 7-S) see Desogestrel a-methylene-4-nitrobenzeneacetic acid methyl ester (CJ0H9NO4 28042-27-5) see Alminoprofen a-methylene-2-(phcnylmethyl)benzeneacetic acid ethyl ester... 

The aldehyde group of laevulinic aldehyde reacted preferentially with the ester phosphorane (38), while the 2-acetyl groups of the benzofurans (39) were selectively methylenated with methylenetriphenylphosphorane. The aldehyde group was protected as the dimethylacetal in the synthesis of the steroidal a-methylene-aldehyde (40). 

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