Keto esters unsaturated

The chiral BOX-copper(II) complexes are effective catalysts for enantioselective cycloaddition reactions of a,/ -unsaturated acyl phosphonates [48] and a,/ -unsaturated keto esters [38b, 49]. 

The Michael reaction occurs with a variety of a,/3-unsaturated carbonyl compounds, not just conjugated ketones. Unsaturated aldehydes, esters, thio-esters, nitriles, amides, and nitro compounds can all act as the electrophilic acceptor component in Michael reactions (Table 23.1). Similarly, a variety of different donors can be used, including /3-diketones, /3-keto esters, malonic esters, /3-keto nitriles, and nitro compounds. 

Unsaturated -Keto Esters, (3-Diketones, and a /3-Keto Sulfoxide Prepared by Selenoxide Elimination... 

The diketones (178 n = 0, 2, 4, 6, or 7) reacted normally with the phosphonate anion (179) to give unsaturated keto-esters. " However,... 

In the early 1990s, Burk introduced a new series of efficient chiral bisphospholane ligands BPE and DuPhos.55,55a-55c The invention of these ligands has expanded the scope of substrates in Rh-catalyzed enantioselective hydrogenation. For example, with Rh-DuPhos or Rh-BPE as catalysts, extremely high efficiencies have been observed in the asymmetric hydrogenation of a-(acylamino)acrylic acids, enamides, enol acetates, /3-keto esters, unsaturated carboxylic acids, and itaconic acids. 

Bicyclic y-lactones,7 These lactones can be obtained by intramolecular reductive cyclization of unsaturated keto esters with Sml2 in THF-HMPT. Example ... 

More complicated substrates such as some dienones and trienediones, required multi-stage syntheses. For example, the unsaturated keto-ester 6 was synthesised via sequential Wittig reactions, (Scheme 7). 

Further research on intramolecular photocyclization of amino enones and amino ketones based on electron transfer has been made by Kraus and Chen [228]. In analogy to the earlier results of Roth and El Raie [229], Kraus and Chen obtain the cyclopropanol derivative 286 as single stereoisomer by direct irradiation of 285. Photolysis of the amino enone 287 does not lead to a three-membered ring product, but only to pyrrolidine 288. The irradiation of the unsaturated keto ester 289 results in the even more unexpected formation of a nine-membered ring product 290. Such remote photocyclizations have rarely been described so far. 

A similar type of acid-catalyzed condensation of aldehydes with 4-methylene-2-oxetanone (diketene), giving 4-oxo-6-methyl-l,3-dioxins, has been patented (73GEP2149650). However, other work has established that <5-hydroxy-/3-keto acids or unsaturated keto acids are formed as the principal products (equation 24) (78CPB3877, 78CL409). The latter reaction probably involves electrophilic attack of the protonated aldehyde on the nucleophilic exocyclic methylene carbon atom of the diketone. A closely related reaction of acetals with diketene, catalyzed by titanium tetrachloride, gives the corresponding <5-alkoxy-/3-keto esters (74CL1189). 

A novel entry to decahydrocyclopentacyclooctene derivatives via the intramolecular photocycloaddition of fused a,/3-unsaturated y-lactones has been developed (80CC1011). Irradiation of the butenolide (153) in acetone solution gave both the fused and bridged photoadducts (154) and (155) (2-3 1). The major adduct was hydrolyzed, oxidized and esterified to afford (156). Reductive cleavage of the unsaturated keto ester (156) with lithium in ammonia afforded a five-component mixture of a,/3- and /3,y-unsaturated esters. Equilibration with 0.1M sodium methoxide in methanol converted the mixture into a single a,j8-unsaturated ester (157 Scheme 34). This annelative two-carbon ring expansion method may find application in the synthesis of ophiobolin and ceroplastol sesterterpenes. 

The same sequence applied to a silyl enol ether of an ester results in a 1,5-unsaturated aldehydo ester (from 1), or a 1,5-unsaturated keto ester (from 2).2... 

In the alternate and unsuccessful approach to haemanthidine (382), which entailed the construction of the D ring prior to the functionalization of the C ring, the ester 458 was converted to the unsaturated keto lactam 468 by a straightforward route analogous with the one discussed above for the transformation of 461 to 463. The carbonyl group at C-6 was then reduced with sodium borohydride to alleviate concern over its reactivity, but epoxidation of the double bond at C-2 and C-3 of 469 afforded a mixture of diastereomeric a- and (3-epoxides. Owing to the lack of stereoselectivity in this crucial step, this route was abandoned (202). 

Walphos (138), developed by Sturm at the University of Vienna and optimized at Solvias, is derived from the Ugi amine 54.174175 Walphos can be electronically fine-tuned as various phosphine groups are introduced in separate steps of the synthesis. Walphos catalysts have been used to reduce enamide esters to a-amino esters, P-keto esters, a,P-unsaturated carboxylic acids, and itaconate esters with enantioselectivities >90%.176... 

For the enantioselective hetero Diels-Alder reaction, very similar bis(oxazoline) complexes proved to be highly efficient [28]. The conversion of several unsaturated keto-esters 59 with ethyl-vinyl ether 60 gave cycloaddition products 61 in 97-99% ee. 

Although the Michael addition of metal ynolates to a,/ -unsaturated carbonyl compounds is expected to give six-membered cycloadducts, 1,2-addition to carbonyl groups usually precedes 1,4-addition. The cycloaddition of the lithium-aluminum ate complex of silyl-substimted ynolate 112 with ethyl benzylideneacetoacetate (113), which is doubly activated by the ester and keto functions, gives the y-lactone 114 via a [4 4- 2] type cycloaddition (equation 46). Diethyl benzylidenemalonate (115) affords the uncyclized ketene 116 by reaction with 112 (equation 47). This could be taken as evidence for a stepwise mechanism for equation 46. ... 

Unsaturated keto esters obtained by the Knoevenagel condensation have been selectively hydrogenated in good yields with Raney nickel catalyst at room temperature and 45 atm. to saturated keto esters, e.g., ethyl a-heptylacetoacetate (97%) from ethyl a-heptylideneacetoacetate. ... 

This reagent readily reduces esters in toluene, hexanes, THF or CH2CI2 solutions, etc. The reaction is especially useful for the preparation of allylic alcohols from a,3-unsaturated esters. 3-Keto esters have been selectively reduced to 3-hydroxy ketones via ketone enolate formation and AIH3 reduction. 

The oxidation of unsaturated esters to unsaturated keto esters is accomplished with chromium trioxide in acetic acid and acetic anhydride. Methyl 2-nonenoate is thus converted in benzene solution at 0-20 °C into methyl 4-keto-2-nonenoate in 86% yield [553],... 

Valuable applications of this principle have been described by Paquette for the synthesis of topologically spheric molecules. Coates used this reductive fragmentation for the synthesis of bicy-clo[6.3.0]undecenecarboxylates, compounds which bear a structural resemblance to the a-b rings of the fusicoccin and ophiobolane natural products. Reduction of the unsaturated keto ester (164) affords an isomeric mixture of esters, the equilibration of which effects conversion to the single ester (165 Scheme 56). 

---