Diels-Alder reaction, with ketones

Hetero Diels-Alder reactions of 3,4-di-fcrf-butyIthiophene 1-oxide with thioaldehydes and thioketones take place exclusively at the syn-jt-face with respect to the S=0 bond, like the Diels-Alder reactions with ketones. Thiophosgene and adamantanethione can also react with 3,4-di-(erf-butylthiophene 1-oxide to afford the corresponding syn-tr-face products (Scheme 44) [49]. 

Myrcene with its conjugated diene system readily undergoes Diels-Alder reactions with a number of dienophiles. For example, reaction with 3-meth.5i-3-pentene-2-one with a catalytic amount of AlCl gives an intermediate monocyclic ketone, which when cyclized with 85% phosphoric acid produces the bicycHc ketone known as Iso E Super [54464-57-2] (49). The product is useful in providing sandalwood-like and cedarwood-like fragrance ingredients (91). 

The ability of 1,2 (or l,6)-dihydropyridines to undergo a Diels-Alder reaction with dienophiles such as methyl vinyl ketone, methyl acrylate, and acrylonitrile has been utilized in the synthesis of polyfunctional isoquinuclidine as a key intermediate in the synthesis of aspidosperma- and iboga-type alkaloids (66JA3099). 

Phenylsulfonyl)indole 330 was converted to a ketone by a set of standard reactions followed by the selenium dioxide oxidation of the resulting acetyl goup to the ketoaldehyde 332 (Scheme 101). Methylthiosemicarbazide hydroiodide reacted with 332 to the triazine 333 in 83% yield. As Diels-Alder reactions with 1 -pyrrolidinocyclohexene failed, 333 was first oxidized... 

Cyclic 1,3-diacetoxy-l,3-dienes can be generated in situ from cyclic 1,3-diketones under the influence of isopropenyl acetate. The dienes then undergo Diels-Alder reactions with maleic anhydride giving as products 1-acetoxybicycloalkane dicarboxylic anhydride derivatives (10). The procedure is also successful with cyclic 1,2- and 1,4-diketones as well as cyclic a,j3-unsaturated ketones. The products, after hydrolysis to... 

The presence of the catalyst can also favor multiple Diels-Alder reactions of cycloalkenones. Two typical examples are reported in Schemes 3.6 and 3.7. When (E)-l-methoxy-1,3-butadiene (14) interacted with 2-cyclohexenone in the presence of Yb(fod)3 catalyst, a multiple Diels-Alder reaction occurred [21] and afforded a 1 1.5 mixture of the two tricyclic ketones 15 and 16 (Scheme 3.6). The sequence of events leading to the products includes the elimination of methanol from the primary cycloadduct to afford a bicyclic dienone that underwent a second cycloaddition. Similarly, 4-acetoxy-2-cyclopenten-l-one (17) (Scheme 3.7) has been shown to behave as a conjunctive reagent for a one-pot multiple Diels-Alder reaction with a variety of dienes under AICI3 catalysis, providing a mild and convenient methodology to synthesize hydrofluorenones [22]. The role of the Lewis acid is crucial to facilitate the elimination of acetic acid from the cycloadducts. The results of the reaction of 17 with diene... 

Similar transformations have been performed with Danishefsky s diene and glyoxylate esters [85] catalyzed by bis (oxazoHne)-metal complexes to afford the hetero Diels-Alder product in 70% isolated yield and up to 72% ee. Jorgensen [86,87] reported a highly enantioselective, catalytic hetero Diels-Alder reaction of ketones and similar chiral copper(II) complexes leading to enantiomeric excesses up to 99% (Scheme 31, reaction 2). They also described [88] a highly diastereo- and enantioselective catalytic hetero Diels-Alder reaction of /I, y-imsaturated a-ketoesters with electron-rich alkenes... 

In the Diels-Alder reaction with inverse electron demand, the overlap of the LUMO of the 1-oxa-l,3-butadiene with the HOMO of the dienophile is dominant. Since the electron-withdrawing group at the oxabutadiene at the 3-position lowers its LUMO dramatically, the cycloaddition as well as the condensation usually take place at room or slightly elevated temperature. There is actually no restriction for the aldehydes. Thus, aromatic, heteroaromatic, saturated aliphatic and unsaturated aliphatic aldehydes may be used. For example, a-oxocarbocylic esters or 1,2-dike-tones for instance have been employed as ketones. Furthermore, 1,3-dicarbonyl compounds cyclic and acyclic substances such as Meldmm s acid, barbituric acid and derivates, coumarins, any type of cycloalkane-1,3-dione, (1-ketoesters, and 1,3-diones as well as their phosphorus, nitrogen and sulfur analogues, can also be ap-... 

The domino process probably involves the chiral enamine intermediate 2-817 formed by reaction of ketone 2-813 with 2-815. With regard to the subsequent cy-doaddition step of 2-817 with the Knoevenagel condensation product 2-816, it is interesting to note that only a normal Diels-Alder process operates with the 1,3-bu-tadiene moiety in 2-817 and not a hetero-Diels-Alder reaction with the 1-oxa-l,3-butadiene moiety in 2-816. The formed spirocydic ketones 2-818/2-819 can be used in natural products synthesis and in medidnal chemistry [410]. They have also been used in the preparation of exotic amino adds these were used to modify the physical properties and biological activities of peptides, peptidomimetics, and proteins... 

Additionally, investigations into imidazolidinone catalysed Diels-Alder reactions (Schemes 2 and 6) [234] have shown that iminium ions of a,P-unsaturated aldehydes and ketones have lower activation barriers for the Diels-Alder reaction with cyclopentadiene than the parent compound (13 and 11 kCal mol", respectively). It was also noted that transition structures show the formation of the bonds is concerted but highly asynchronous. 

The enedione (15), a tetracyclic intermediate on a synthetic route to fusidic acid, has been synthesized from the a-methylene-ketone (16) (Scheme 2). The first step, involving a Diels-Alder reaction with a substituted acrylate (17), provides a new versatile annelation procedure. Further modification of (15) by a route worked out on model systems (see Vol. 4, p. 318) afforded the tetracyclic enone (24) with the desired trans-syn-trans geometry (Scheme 3). This compound (24) has also been prepared by degradation of fusidic acid. Attempts to introduce the C-11 oxygen function necessary for the synthesis of fusidic acid have not been very... 

Where the carbon-carbon double bond is a part of an aromatic system, in general, cyclopropanation of diazoketones results in the formation of unstable cyclopropane adducts. For example, Saba140 has shown that in the intramolecular cyclopropanation of diazoketone 57 the norcaradiene ketone 58 can be detected by low-temperature NMR and can be trapped in a Diels Alder reaction with 4-phenyl-l,2,4-triazoline-3,5-dione (equation 69). In addition, Wenkert and Liu have isolated the stable norcaradiene 60 from the rhodium catalysed decomposition of diazoketone 59 (equation 70)105. Cyclopropyl ketones derived from intramolecular cyclopropanation of hetereoaromatic diazoketones are also known and two representative examples are shown in equations 71 and 72106. Rhodium(II) compounds are the most suitable catalysts for the cyclopropanation of aromatic diazoketones. 

Linders, J.T.M., Briel, P., Fog, E., Lie, T.S. and Maat, L., Chemistry of opium alkaloids, Part XXVIII preparation of 6-demethoxy-N-formyl-N-northebaine and its Diels-Alder reactions with methyl vinyl ketone and nitroethene novel 8-nitro-substituted 6a,14a-ethenoisomorphinans and 6 3,14 3-ethenomorphinans, Rec. 

A.2.4. Asymmetric Diels-Alder Reactions with Unsaturated Ketones... 

Selenoketones.1 Selenoketones can be prepared by reaction of dialkyl ketones with 1 and trapped by a Diels-Alder reaction with a diene. A sterically hindered selenoketene, selenofenchone, has been isolated from this reaction. 

Diels-Alder reactions with electron-rich alkenes.1 Simple a,(i-unsaturated im-ines (1-aza-1,3-butadienes) do not undergo Diels-Alder reactions with dienophiles. In contrast, the N-phenylsulfonyl imines derived from an aldehyde or ketone undergo Diels-Alder reactions under forcing conditions with electron-rich dienophiles to... 

In order to introduce functionality at key positions, an intramolecular Diels-Alder reaction with furan as the diene component was planned. Suzuki coupling of the previously mentioned 105 with furan-3-boronic acid 106 gave compound 107, which was N-tosylated to 108. Construction of the dienophile portion was performed as in the previous case, by addition of vinylmagne-sium bromide to give 109, followed by MnC>2 oxidation to give the cyclization precursor, which was immediately heated at 120 °C in toluene and afforded compound 110, which incorporates an oxygen atom at both the ketone and vinyl chloride positions of welwistatin (Scheme 24). 

Diels-Alder reactions of the type shown in Table 15.1, that is, Diels-Alder reactions between electron-poor dienophiles and electron-rich dienes, are referred to as Diels-Alder reactions with normal electron demand. The overwhelming majority of known Diels-Alder reactions exhibit such a normal electron demand. Typical dienophiles include acrolein, methyl vinyl ketone, acrylic acid esters, acrylonitrile, fumaric acid esters (irans-butenedioic... 

Diels-Alder reactions carbohydrates.2 This 3,y-unsaturated a-keto ester undergoes Diels-Alder reactions with electron-rich dienophiles to provide protected sugars. The thermal and pressure-promoted reaction of 1 with ethyl vinyl ketone provides the endo-adduct 2, which can be converted in two steps into the ethyl (3-mannopyranoside 3. The same reaction of 1 with (Z)-l-acetoxy-2-benzy-loxyethylene is even more endo-selective, and gives the endo-adduct 4, which can be converted into a derivative of benzyl DL-mannopyranoside. 

These ketones undergo Diels-Alder reactions with dienes to give selenopyrans in good to excellent yields. 

Northrup AB, MacMillan DWC (2002a) The first direct and enantioselective cross-aldol reaction of aldehydes. J Am Chem Soc 124 6798-6799 Northrup AB, MacMillan DWC (2002b) First general enantioselective catalytic Diels-Alder reaction with simple alpha,beta-unsaturated ketones. J Am Chem Soc 124 2458-2460... 

Scheme 1.20. Double Michael-type addition of dienolate 220 to Cgo, affording after workup the thermodynamically more stable Irans-disubstiluted ketone ( )-219. Due to steric congestion, the corresponding civ-adduct is not available through Diels-Alder reaction with the silyl enol ether corresponding to 220. Reduction of the racemic ketone ( )-219 with DIBAL-H diastereoselec-tively affords alcohol ( )-223.

Northrup, A. B. MacMillan, D. W. C. The first general enantioselective catalytic Diels-Alder reaction with simple a,p-unsaturated ketones, J. Am. Chem. Soc. 2002, 124, 2458-2460. 

Table 7. [4+2] Hetcro-Diels-Alder Reactions with a,/i-Unsaturatcd Trifluoro-methyl Ketones ...

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