Esters addition to a,/?-unsaturated

The addition to a, -unsaturated esters is usually difficult. However, under appropriate conditions, the 1,4-addition of diorganozincs to enoates is possiblc As mentioned above, Michael-addition reactions can also be catalyzed by Ni(II) salts . The 1,4-addition of functionalized organozinc iodides to enones in the presence of Ni(acac)2, a diamine as ligand and TMSCl provides, after hydrolysis, the Michael adducts in satisfactory yields . 

Conjugate addition to a, -unsaturated esters.1 The unsaturated esters of this phenol undergo ready conjugate addition with a variety of organolithium reagents, with t-butyllithium providing the only exception. The adducts are oxidatively hydrolyzed to carboxylic acids by CAN (10, 162). 

See page 1809, Section 6 for analogous conjugate additions to a,/ -unsaturated, esters and nitriles. 

The ate complex [MgBr]+[Bu2SnBrIH promotes the conjugate addition to a,/ -unsaturated esters (Equation (29)). u The results that non-substituted alkenes are more reactive than the substituted ones indicate an ionic mechanism for this hydrogenation, because the reactivity order is reverse in the radical reactions where the non-substituted unsaturated esters are unreactive.91... 

Treatment of a (2.2.1)-bicyclic amine with BuLi gives a chiral lithium amide that undergoes highly stereoselective Michael additions to a, -unsaturated esters (eq 70). Treatment with A-iodosuccinimide releases the chiral auxiliary as the bornylalde-hyde and furnishes the optically active /3-amino esters. 

Enamine addition to an unsaturated ester, followed by an intramolecular alkylation, provided a facile synthesis of an adamantane bis-/3-ketoester 674). Michael addition of pyrrolidinocycloheptene to other acrylic esters 668) and of other enamines to acrylic acids 675), a chloroacrylonitrile 676), and an unsaturated cyanocarboxamide (577) were reported. 

Closely related to enolate additions to enones is the diastereoselective 1,4-addition of lithium enolates of esters, thioesters and amides to a,/ -unsaturated esters. These reactions provide syn-or ar /-2,3-disubstituted glutarates (pentanedioates). 

The addition of a-amino-substituted lithium enolates to a,/ -unsaturated esters is a diastereoselective route to syn- or anti-glutamic acid derivatives and also to fratw-substituted 5-oxo-2-pyrrolidinecarboxylates. 

Under thermodynamically controlled conditions, using triethylamine as base for the addition of enones to 5 and sodium methoxide in methanol as base for the addition of a,/ -unsaturated esters, the diastereomeric ratios of 6 range from 95 5 to 97 3. The excellent diasteroselectivities are retained in the Michael addition of 5 to -substituted enones and esters, however, modest synjami selectivities are found212,213. 

Palladium-catalyzed bis-silylation of a,/ -unsaturated ketones using bis(disilanyl)dithiane affords seven-membered ring silyl enol ethers in high yields via 1,4-addition (Equation (48)).8,97 Application of this reaction to a,/ -unsaturated esters and nitriles gives five-membered ring 1,2-addition products in good yields (Equation (49)). 

TABLE 9. Asymmetric conjugate addition of organolithium reagents to a,/ -unsaturated esters and imines in the presence of chiral diether hgand 28 or (—)-sparteine (29) ... 

For a Rh-catalyzed asymmetric conjugate addition of arylboronic reagents to a,/)-unsaturated esters, see S. Sakuma, M. Sakai, R. Itooka and N. Miyaura, J. Org. Chem., 65, 5951 (2000) and references cited therein. 

Use of BF3 etherate as catalyst was suggested by the report of Yamamoto and Maruyama4 that -C,H(iCu complexed with BF3 undergoes conjugate addition to a,/ -unsaturated acids and esters, a reaction that has not been observed with R CuLi, even in the presence of BFj etherate. 

The addition of diazomethane to a,/ -unsaturated esters (1), as ethyl acrylate, methyl crotonate and ethyl cinnamate, was investigated by Auwers181 who showed that the primary addition product is a A pyrazoline (2) which rearranges spontaneously to the conjugated A2-pyrazoline (3). 

Michael addition. DABCO is a particularly effective catalyst for Michael addition of /f-keto thiolesters to a,/ -unsaturated esters and ketones. The addition to enones provides an attractive route to 1,5-diketones that can undergo annelation to fused or... 

This reaction can be used to effect conjugate addition of an alkyl group to a,p-unsaturated sulfoxides, which is generally unsatisfactory with RMgBr or R2CuLi. However, nitroalkanes undergo this 1,4-addition in the presence of a base, particularly DBU, and the product can be selectively reduced to the desired sulfoxide. The same conditions can be used to effect conjugate addition to a,/ -unsaturated ketones and esters.10... 

Cerium(IV) ammonium nitrate (CAN) has been reported to catalyse a facile and efficient aza-Michael addition of aromatic and aliphatic amines to a -unsaturated esters in the absence of solvent under ultrasound irradiation.136 a,/l-Unsaturated ketones react in aqueous solutions under these conditions but only with aliphatic (not aromatic) amines.137... 

Y. Stereoselective conjugate addition of an a-sulfmyl carbanion to a,/ -unsaturated esters asymmetric synthesis of cycloalkanecarboxy-lates. Synlett 1997, 449-450. 

Silylene transfer to a -unsaturated esters produces oxasilacyclopentenes and provides a new method for regio- and stereo-selective formation of enolate that can undergo facile and selective Ireland-Claisen rearrangements and aldol addition reactions to provide products with multiple contiguous stereocenters and quaternary carbon centers (Scheme 37). 

The enolate derived from the Schiff base 3 has been added to a,/ -unsaturated esters and ketones with a high level of enantioselectivity. For example, in the presence of 10 mol% lb, the enolate of the glycine derivative 3 was added to cyclohexenone with excellent diastereo-selectivity to give the ketoester 20 with >99% ee (Scheme 7) [15]. Promising results have also been obtained in the Michael additions of malonates to chalcone deriviatives [16], The novel cinchonidinium bromide lg was found to be the most effective catalyst for this transformation, yielding the Michael adduct 21 with 70% ee (Scheme 8). 

Addition reactions of organoboronic acids to electron-deficient alkenes were found to be catalyzed by rhodium(i)931 or dicationic palladium(n) complexes.932,933 The reaction proceeding through the transmetallation to a transition metal has been proved to be a general technique for a wide range of selective carbon-carbon bond formation via 1,4-addition to a,/ -unsaturated ketones, aldehydes, esters, and amides, and the 1,2-addition to aldehydes and imines (Equation (217)).934... 

If cyclization is to be followed by decarboxylation, a cunning plan can be set in motion. Addition of an amine by an S 2 reaction to an a halo-ester followed by conjugate addition to an unsaturated ester gives a substrate for Claisen ester cyclization. 

Michael addition to a, -unsaturated aldehydes The Michael addition of malonic ester and acetoacetic ester to a,0-unsaturated aldehydes can be carried out in moderate yields under phase-transfer conditions with sodium or potassium carbonate as base and benzyltriethylammonium chloride as catalyst (equation I). 

Addition of optically active 1-phenylethylhydroxylamines to a,/ -unsaturated esters proceeds in good yield but with modest diastereoselectivity for the isolated substituted /J-amino acid esters12. Thus, reaction of (S)-l-phenylethylhydroxylamine with methyl 2-methylpropenoate in diethyl ether affords the corresponding conjugate-adduct in 86% yield12. This is subsequent-... 

Intramolecular conjugate-type addition of the anions of A -[(5)-l-phenylethyl]amides 1 to a,/ -unsaturated esters results in the formation of cyclic acetic acid derivatives 231-33. 

There are many examples of Ihe simultaneous addition of fluorine and bromine to a,/ -unsaturated esters.174,1 75-1 99,2 u 241-246-2 52,298... 

The main product in hydrosilation of a,P-unsaturated ketones and aldehydes catalyzed by chloro-platinic acid, platinum on alumina, or metallic nickel is the corresponding silyl enol ether. With nickel catalyst, product distribution is highly dependent on the enone structure. Hydridosilanes add to a, -unsaturated esters, producing the corresponding silyl enolate as well as carbon silylated products. The course of addition depends on substrate structure and the hydridosilane utilized. Thus, triethylsilane undergoes 1,4-addition to methyl acrylate in the presence of chloroplatinic acid, while trichlorosilane with either chloroplatinic acid or Pt/C gives the -silyl ester (Scheme 65). ... 

Treatment with the tertiary amine forms the anions of the carboxylic acids. That of B can do a conjugate addition to the unsaturated ester and form the lactone but the carhoxylate of A cannot react. 

---