Keto esters 3,2 -cycloaddition

In the presence of a double bond at a suitable position, the CO insertion is followed by alkene insertion. In the intramolecular reaction of 552, different products, 553 and 554, are obtained by the use of diflerent catalytic spe-cies[408,409]. Pd(dba)2 in the absence of Ph,P affords 554. PdCl2(Ph3P)3 affords the spiro p-keto ester 553. The carbonylation of o-methallylbenzyl chloride (555) produced the benzoannulated enol lactone 556 by CO, alkene. and CO insertions. In addition, the cyclobutanone derivative 558 was obtained as a byproduct via the cycloaddition of the ketene intermediate 557[4I0]. Another type of intramolecular enone formation is used for the formation of the heterocyclic compounds 559[4l I]. The carbonylation of the I-iodo-1,4-diene 560 produces the cyclopentenone 561 by CO. alkene. and CO insertions[409,4l2]. 

The stereochemistry of the product formed in the cycloaddition reaction depends on the approach of the substrate. There are two different approaches by which the reaction can proceed - endo and exo. For the reaction of e.g., a / , y-un-saturated a-keto ester with an ethyl vinyl ether there are four possible approaches... 

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]. 

Our development of the catalytic enantioselective inverse electron-demand cycloaddition reaction [49], which was followed by related papers by Evans et al. [38, 48], focused in the initial phase on the reaction of mainly / , y-unsaturated a-keto esters 53 with ethyl vinyl ether 46a and 2,3-dihydrofuran 50a (Scheme 4.34). 

Cycloaddition of 2-cyanoalk-2-enones with several conjugated dienes proceeded under zinc chloride catalysis.636 Zinc halides have also shown reactivity with phenylacetylenes.637 Zinc chloride is an effective Lewis acid catalyst in the Diels Alder reactions of the keto esters and the effects on stereochemistry of catalysts used have been examined.638... 

Combinatorial solution-phase cycloadditions of (1Z,4R, 5R )-4-benzoylamino-5-phenylpyrazolidin-3-on-l-azomethine imines 320 to 3-keto esters afforded a library of 26 highly pure bicyclic pyrazolidinones 713 in 6-89% yields and in 14-100% de. Most of the products were isolated as mixtures of the major (13, 23, 3/ , 5/ , 6/ )-epimers 713 and the minor (1R, 2A, 3R, 5R, 6R )-epimers 714 (Scheme 113). Epimerization of these cycloadducts at the anomeric position in solution was confirmed by H NMR spectroscopy <2007MI717>. 

Evans et al. (219, 220) examined the use of electron-poor heterodienes as partners in cycloadditions with electron-rich alkenes under copper catalysis. In particular, a,p-unsaturated acylphosphonates and keto-esters afford hetero-Diels-Alder adducts in high selectivities when treated with enol ethers in the presence of catalysts 269c and 269d. 

The meso-ionic 1,3-oxazol-S-ones show an incredible array of cycloaddition reactions. Reference has already been made to the cycloaddition reactions of the derivative 50, which are interpreted as involving cycloaddition to the valence tautomer 51. In addition, an extremely comprehensive study of the 1,3-dipolar cycloaddition reactions of meso-ionic l,3-oxazol-5-ones (66) has been undertaken by Huisgen and his co-workers. The 1,3-dipolarophiles that have been examined include alkenes, alkynes, aldehydes, a-keto esters, a-diketones, thiobenzophenone, thiono esters, carbon oxysulfide, carbon disulfide, nitriles, nitro-, nitroso-, and azo-compounds, and cyclopropane and cyclobutene derivatives. In these reactions the l,3-oxazol-5-ones (66)... 

Pyranone 127 reacts with alkenes in the presence of cerium ammonium nitrate via a cyclization reaction that leads to the formation of furo[2,3-3]- and furo[3,2-f]-pyranones in moderate yields (Equation 60). This reaction can be extended to the synthesis of furoquinolinones <1999H(51)2881>. Dihydropyran 128, with either / -diketones or /3-keto esters, undergoes cycloaddition reactions promoted by ceric ammonium nitrate to generate furo[2,3-3]pyrans in good yields (Equation 61) <1996T12495>. 

A recent example of this intramolecular tandem transformation is the Rh(ii)-catalyzed reaction of diazo keto ester 71. Depending on the structure of the diazo compound, a push-pull dipole intermediate derived from 71 can be trapped either by a tethered vinyl group (when n = 0) or by an indole 7r-bond (when n=l) (Equation (11)). This result clearly demonstrates a critical role of the conformation of the cycloaddition transition state. 

Some variation is acceptable in the structure of the carbonyl component and unsaturated ketones, aldehydes, esters and j8-keto esters have been used (76T1449). The first type offers the best yields and this may well be a consequence of a competing [2 + 2]-cycloaddition which is observed with unsaturated aldehydes and esters (Scheme 21) (70TL885). 

The thermal ring opening of the pyrazoline (351) occurs with elimination of nitrogen and the formation of a keto ester. The latter cyclizes with loss of ethanol to the pyran-2-one (352 Scheme 110) (02CB782). Since pyrazolines may be obtained from a 1,3-dipolar cycloaddition of diazoacetic ester and an unsaturated ketone, this route is in effect a further example of a type (i) synthesis (Scheme 85). 

Enandoselective tandem carbonyl ylide formation-cycloaddition of a-diazo- -keto esters is achieved in hexane with [Rh2(5-DOSP)4] (1 mol %) at room temperature to give the corresponding cycloadducts with moderate enantioselectivity [73] (Eq. 8A.49). 

The catalytic asymmetric dipolar cycloaddition reactivity of in rt/ -formed 2-benzopyrylium-4-olates (e.g., 139) with a variety of dipolarophiles including a-alkoxy ketones 140, cr-keto esters 141, and acryloyl oxazolidinones 142 has been extensively studied (Scheme 16) <20000L3145, 2002JA14836, 2003S1413, 2005JOC47, 2006T9218>. 

Scheme 1 a The [2 + 2] cycloaddition product of prochiral trans 2-butene with Si dimers of the Si(100) surface leads to chiral adsorbate complexes, b Hydrogenation of prochiral a-keto esters over platinum is a heterogeneously catalyzed reaction leading to chiral alcohols. Using cinchonidin as chiral modifier makes this surface reaction enantioselective. In a similar fashion, TA-modified nickel is a highly enantioselective catalyst for /3-keto ester hydrogenation... 

One intramolecular Diels-Alder cycloaddition which does not involve a ring as a starting point has been described. The sequence commences with allylic / -keto ester derivatives (201) and ends with the formation of the highly reduced furopyridazine (202 R = 2,4-dinitrophenyl or benzoyl) (Equation (70)) <89JCS(P1)353>. 

The synthesis of polysubstituted tetrahydrofurans was also achieved in a stereoselective manner by a formal [3+2] cycloaddition of an allylsilane with a-triethylsiloxy aldehydes. An example showing the mechanism is illustrated <02JA3608>. In another approach, allylsilane was also allowed to react with a-keto esters in a [3+2] annulation reaction, providing highly substituted tetrahydrofurans in good yields as single diastereomers <02OL2945>. 

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. 

Cyclopropenone ketals can undergo a similar [3 -I- 2] cycloaddition with aldehydes or ketones to provide butenolide ortho esters, which in turn can be converted into butenolides, furanes, or y-keto esters. ... 

During the synthesis of the Woodward reserpine precursor (17 Scheme 4), Peailman used the protected acylacetal (13) to control the stereochemistry of an intramolecular photochemical cycloaddition to (14). The strategy for opening the cyclobutane ring employed the Baeyer-Villiger reaction to convert the 7-keto ester (15) to a 3-hydroxy ester (16), which underwent retroaldolization to (17). 

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