Enoates cyclic

The use of nonstabilized carbon nucleophiles in this reaction has been rare. Recently, however, it was shown that lithium ester enolates participate in Pd-cata-lyzed 1,4-additions to cyclic and acyclic vinyloxiranes, affording the corresponding 6-hydroxy-4-enoates in good yields and with complete regioselectivity [117, 118]. 

An extensive paper by Burgada et l. reports the reactions of cyclic phosphites (75 ab) and cyclic phosphoramidites (76 ab) with trans-1,2-dibenzoylethene, methyl fumarate, benzalacetone (PhCH=CH COMe), methyl-4-keto-pent-2-enoate (MeCO.CH=CH.COgMe) and benzalacetophenone (PhCH=CHCOPh)95. These reactions lead to... 

Figure 3.33. Scope of Rh/(5)-binap-catalyzed as5mimetric 1,4-addition of arylboronic acids to a cyclic a,P-enoate.

The intramolecular 2 + 2-photo-cycloadditions of optically active allenesilanes (5) with enones and enoates produce silyl-substituted exo-methylenecyclobutanes (6) in high enantiometric excess. Photo-desilation leads to the parent unsaturated exo-methylenecyclobutanes (7) (Scheme 3).19 The cycloaddition of naphthoquinone to allyltrimethylsilane in the presence of Me2 A1C1 yields the expected 2 + 2-cycloadduct that slowly rearranges to the 2 + 3-adduct.20 hi the presence of bases, Cephalosporin triflates (8) undergo 2 + 2- and 4 + 2-cycloaddition with alkenes, alkynes, and dienes via an intermediate six-membered cyclic allene (9) (Scheme 4).21... 

Das and co-workers have described the generation of a-aminoalkyl radicals from cyclic secondary amines using anthraquinone-photocatalysis [95JCS(P1)1797]. The conjugate addition of the a-aminoalkyl radical to enoates has been examined. The cyclized compound is obtained directly from the reaction. The chemical yield of 149 is low and it is accompanied by 148, a product arising from nucleophilic addition of the amine to the crotonate. 

The last results reported in this field are related to the 1,3-dipolar reactions of tert-butyl ( )-4,4-diethoxy-2-p-tolylsulfinylbut-2-enoate and (S5,Ss) and (R5,Ss) 5-ethoxy-3-p-tolylsulfinylfuranones (42a and 42b) with different nitrile oxides [ 167]. Acyclic sulfoxides react with benzonitrile, acetonitrile, and bromo-formonitrile oxides to yield isoxazoles resulting in desulfinylation from the adducts. Cyclic dipolarophiles afford bicyclic isoxazolines in their reactions with benzonitrile oxide. The reactivity of the double bond as a dipolarophile is strongly increased by the sulfinyl group. The regioselectivity of these reactions... 

Besides simple enones and enals, less reactive Michael acceptors like /3,/3-disubstituted enones, as well as a,/3-unsaturated esters, thioesters, and nitriles, can also be transformed into the 1,4-addition products by this procedure.44,44a,46,46a The conjugate addition of a-aminoalkylcuprates to allenic or acetylenic Michael acceptors has been utilized extensively in the synthesis of heterocyclic products.46-49 For instance, addition of the cuprate, formed from cyclic carbamate 53 by deprotonation and transmetallation, to alkyl-substituted allenic esters proceeded with high stereoselectivity to afford the adducts 54 with good yield (Scheme 12).46,46a 47 Treatment with phenol and chlorotrimethylsilane effected a smooth Boc deprotection and lactam formation. In contrast, the corresponding reaction with acetylenic esters46,46a or ketones48 invariably produced an E Z-mixture of addition products 56. This poor stereoselectivity could be circumvented by the use of (E)- or (Z)-3-iodo-2-enoates instead of acetylenic esters,49 but turned out to be irrelevant for the subsequent deprotection/cyclization to the pyrroles 57 since this step took place with concomitant E/Z-isomerization. 

Intramolecular conjugate addition naturally results in ring formation. The body of examples of this type of reaction is subdivided into the Sections 4.7.1.1.2.1. Acyclic Acceptors and 4.7.1.1.2.2. Cyclic Acceptors , depending on whether or not the accepting enone/enoate moiety is part of a ring system. In the latter case, the cyclization affords a bi- or oligocyclic product. The steric restrictions thus imposed reduce the number of thermodynamically feasible products. As a consquence, product structures can usually be predicted easily, and high stereoselectivities are observed. 

The combination of diethylzinc and chloroiodomethane was employed in the synthesis of carbo-cyclic cyclopropyl nucleosides projected for biological evaluation. Attempts to cyclopropanate the intermediate a,j8-unsaturated ester, methyl (Z)-4,5-(isopropylidenedioxy)pent-2-enoate, gave a low yield (10%) of the desired cyclopropyl product. However, hydroxy-directed cyclo-propanation vide infra) of the reduced allyl alcohol 21 with diethylzinc/chloroiodomethane at 0°C afforded the cyclopropane derivative 22 in 54% yield. 

A tandem cyclopropanation/Cope rearrangement sequence precluded the isolation of the bi-cyclic c -l,2-divinylcyclopropane9, when ( , )-hexa-2,4-dienyl 2-diazo-4-phenylbut-3-enoate and related dienylic esters were catalytically decomposed. When the double bond next to the tether had the Z configuration, however, the diastereomeric tra 5-l,2-divinylcyclopropane was formed and isolated it underwent the Cope rearrangement leading to the same product 10 only at 140 C. ... 

Stereoselective epoxidation of enoates. The final step in the synthesis of (+)-aphidicolin (4) requires a stereoselective conversion of the cyclic norketone (I) to a Wol,2-diol, >C(0H)-CH20H. Methylcnation of the ketone followed by a Sharpless asymmetric dihydroxylation provides a 1 1 mixture of epimcric 1,2-diols. Reaction with a chiral oxaziridinc also provides a 1 1 mixture of cpimcric epoxides. The transformation is effected successfully by conversion of the ketone to the enol triflate, which is converted to the enoate (2) by Pd-catalyzed carbonylation in methanol (13,234). Epoxidation of 2 with m-CPBA in buffered CH2CI2 with a radical scavenger (4,85-86) results in a single epoxy ester (3) in 90% yield. This product is reduced with lithium aluminum hydride (excess) to aphidicolin (4) in 67% overall yield from the ketone 1. 

Cyclization onto an enone or enoate provides an alternative method to access a cyclic product with suitable functionality for further elaboration. Thus, a key step in a synthesis of the alkaloid gelsemine made use of the radical cyclization after homolytic C—S bond cleavage of the sulfide 68 (4.60). A second radical cyclization was subsequently used to set up the indolinone ring of the natural product. 

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