Esters organozinc derivatives

All alkyl halides used in the couplings were primary, although some of them were branched or had an ester functionality. Some of the dialkylzincs had a functional group without affecting the outcome of the reaction. For example, organozinc derivative 302 with a silyl enol ether group reacted with alkyl iodide 303, affording the desired product 304 in 65% yield (Scheme 153). 

One of the most recent developments in the field of Ni-catalyzed reactions of alkyl halides with organozinc derivatives is a study of Terao et al.411 They reported the use of three additives in the couplings 1,3-butadiene, N,N-bis(penta-2,4-dienyl)benzylamine 308a, and 2,2-bis(penta-2,4-dienyl)malonic acid dimethyl ester 308b. Addition of tetraene 308b to the reaction mixtures significantly increased the product yields (Scheme 157). The remarkable effect of these additives was explained by the formation of the bis-7r-allylic complex 309 as the key intermediate (Scheme 158). 

An enantioselective synthesis of ferrocenyl-modified alanines 91 and 93 was also reported.163 In this case, an organozinc derivative of serine 90 was coupled to iodoferrocene 89 or 1,1 -diiodoferrocene 92 using a palladium catalyst [Pd2(dba)3] to give the Boc-ferrocenyl-L-ala-nine methyl esters 91 and 93 in 60 and 64% yield, respectively (Scheme 26). 

Reformatskii reaction. Condensation of carbonyl compounds with organozinc derivatives of a-halo esters to yield (i-hydroxy esters. 

The organozinc compound first formed is unstable therefore the reaction is carried out in such a way that the carbonyl compound to be added to the ester is present during formation of the organozinc derivative. The primary products are the /3-hydroxy esters, as illustrated (a hydracrylic ester from... 

Besides the aldol reaction to form y0-hydroxyketone, 1,3-Dipolar Cycloaddition can also form similar molecules. In addition to the Mukaiyama Aldol Reaction, the following are also similar or closely related to the aldol reaction the Claisen-Schmidt Condensation (the aldol reaction between benzaldehyde and an aliphatic aldehyde or ketone in the presence of relatively strong bases to form an o, )0-unsaturated aldehyde or ketone), the Henry Reaction (base-catalyzed addition of nitroalkane to aldehydes or ketones), the Ivanov Reaction (the addition of enediolates or aryl acetic acid to electrophiles, especially carbonyl compounds), the Knoevenagel Reaction (the condensation of aldehydes or ketones with acidic methylene compounds in the presence of amine or ammonia), the Reformatsky Reaction (the condensation of aldehydes or ketones with organozinc derivatives of of-halo-esters), and the Robinson Annulation Reaction (the condensation of ketone cyclohexanone with methyl vinyl ketone or its equivalent to form bicyclic compounds). 

Condensation of aldehydes or ketones with organozinc derivatives of oc-halo esters to yield (3-hydroxy esters ... 

The carbonyl substrate 3 to be reacted with the organozinc compound 2 can be an aldehyde or ketone that may contain additional functional groups. With a vinylogous halo ester—i.e. a y-halocrotyl ester—the corresponding y-crotylzinc derivative is formed. 

The benzotriazole derivatives 111, obtained from benzotriazole, ethyl glyoxylate and secondary amines (diethylamine, pyrrolidine, piperidine or morpholine), furnish the amino esters 112 by the action of organozinc reagents R2ZnX (R2 = Me, Bu, PhCH2 or Ph)120. 

In several of the previously described methods the anion of the three-carbon fragments was added to an a-amino aldehyde to construct a C—C bond between the C3 and C4 atoms of the 1-hydroxyethylene isostere. However, Sakurai et al.[27l used an add chloride instead of an a-amino aldehyde. They synthesized 6-phthalimido-y-oxo esters by a palladium-catalyzed reaction between acid chlorides and organozinc reagents derived from p-iodo esters. Then, the oxo esters were converted into the y-lactone precursors. 

The intramolecular Wurtz-type coupling of dihaloorganic compounds with use of metallic zinc is a classical synthetic route to cyclic compounds. For example, cyclopropane derivatives can be prepared from 1,3-dihalo-propanes (29, 189a, 248, 451), and cyclobutane derivatives from 1,4-dihalobutanes (71). These reactions presumably proceed via the intermediate formation of organozinc compounds. The reaction of diethylzinc with esters of a,a -dibrominated aliphatic dicarboxylic acids leads to the... 

Zinc-copper couples are used in reactions of a Zn derivative of an a-bromoester with an aldehyde or ketone, or even with a-chloroalkyl esters , and in reactions of CH2I2 and Zn in cyclopropane formation from alkenes, CH2I2 and Zn. In the CH2l2-Zn-Cu reactions the organozinc trapped by MejSnX is IZnCH2l, whereas in the CH2l2-Zn dust-MejAl reaction the trapped species is (IZn)2CH2-... 

The acylation of organozinc reagents derived from dialkyl 1-bromo-1,1-difluoromethylphosphonates with acyl chlorides proceeds smoothly at room temperature to afford the desired products in moderate to good yields (60-77%, Scheme 3.75). Esters, lactones, and triflates did not react at all, even at Although these zinc and cadmium reagents appear to have similar reactivities,... 

The most recent publication in the field of catalytic asymmetric alkylation of nitrones with organozinc reagents has documented the use of bis-alkoxides derived from (R, R)-tartaric acid esters as new chiral catalysts for this reaction (Scheme 19) [40]. Ukaji, Inomata and co-workers were interested in further improving their own method for practical use especially in regard of catalyst availability. Both enantiomers of tartaric acid esters 41 are readily available. 

Cure and Gaudemar5 report that yields in the Reformatsky reaction are generally improved if the reaction is carried out in two steps. First, the a-bromo ester (1) is converted into an organozinc bromide (2) by reaction with zinc in pure and dry dimethoxymethane.6 This derivative is apparently formed in almost quantitative yield. The aldehyde or ketone is then added at 0°. The /3-hydroxy ester is obtained in about 60-90% yield. 

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