Dienophiles cyclohexenones

Conjugated cyclohexenones [6] have also been easily prepared by combining the cycloaddition of dimethylaminobutadiene 4 and several cyclic and acyclic dienophiles followed by the elimination of the amino group from the cycloadducts under acidic conditions. Scheme 2.3 summarizes some of these results. 

Similarly, cycloaddition of the cyclohexenone-like dienophile 40 with 2-tri-methylsilyloxy-1,3-butadiene (41) allowed [7] the regio- and stereoselective synthesis of tetracyclic compound 42, in high yield (Equation 5.5). 

Cationic oxazaborolidines derived from a,a-diphenylpyrrolidine-2-methanol have been examined and shown to considerably extend the range of dienophiles that are responsive to the catalysts." The best proton source for activation of these catalysts is triflimide, (CF3S02)2NH.100 For example, cyclohexenone and cyclopentadiene react with 93% enantioselectivity using catalyst J. 

While doubly activated dienophiles gave moderate to good yields under thermal conditions (Table 11), mono activated alkenes such as cyclohexenone (123) failed to react at temperatures up to 150 °C but underwent cycloaddition under Lewis-acid catalysis even if with poor yields (Table 12, entries 1-3) [32],... 

Thus, if you look at the different dienophiles in Fig. 2.1, the dimerization of butadiene 2.1 is slower than its reaction with acrolein 2.4. Methyl acrylate and methyl vinyl ketone have electron-withdrawing substituents Z of comparable power, and react at a similar rate, but cyclohexenone 2.5, which has a (5-alkyl substituent, is considerably less reactive. Nitroethylene has one of the most powerful electron-withdrawing groups, and is a very good... 

From the retrosynthetic perspective (Fig. 2), the tetracyclic structure is expected to be accessible by tandem Michael-Dieckmann type reaction of 59 with 60. The suitably substituted chiral intermediate 59 would be synthesized by Diels-Alder reaction of the cyclohexenone 57 and the silyloxybutadiene 58. The regio- and stereoselectivities are established as a consequence of the dienophile geometry according to Gleiter s theory (29). Compound 57 could be obtained from 51 through Ferrier reaction of 54. 

Discussion Taddol-catalyzed DA reactions provide simple and direct routes to functionalized cyclohexenones in enantiomerically enriched form. As with the HDA reactions, the best results were obtained when pure diene and dienophile were used, and the reaction temperature was rigorously maintained. Traces of moisture or acid impact negatively upon diene stability and product enantio-purities. One important advantage of the method is the commercial availability of both taddol catalyst 119 and the diene. The best substrates for the taddol-catalyzed DA reactions were a-substituted acroleins. This reactivity profile is complementary to that found for the secondary amine-based organocatalysis developed by MacMillan and co-workers, in which -substituted acroleins provided the best results [116]. 

Trifluoroethyl 2-(trifluoromethyI)prop-2-enoate reacts with various dienes to provide cycloadducts in high yields. A typical example is the reaction with ( )-l-methoxy-2-methyl-3-(trimethylsiloxy)buta-l,3-diene leading to the trifluoromethyl-substituted cyclohexenone 13 which was used as a precursor of 16,16,16-trifluororetinal." The reaction has also been performed with a chiral dienophile."... 

One of the most popular dioxygenated dienes is l-methoxy-3-trimethylsilyloxy-1,3-butadiene (109), the so-called Danishefsky diene (Scheme 30). The elegant application of this and related polyoxygen-ated dienes in synthesis was reviewed in 1981. ° [4 + 2] Cycloadditions of diene (109), wifo typical electron-poor dienophiles, display increased reactivity and legiochemical control owing to die synergism of die two oxygen atoms. Acidic hydrolysis of the initial cycloadducts readily affords cyclohexenones, phenols or cyclohexadienones (c/. Action 4.1.2, Schemes 12, 17,18 and 21). A pertinent example is the... 

The Diels-Alder reaction of 3,6-dimethoxybenzocyclobutene 30 with some dienophiles was studied (Scheme 9). A mixture of benzocyclobutene 30, A -phenyl-maleimide 54, and benzene was heated at 210 in a sealed tube. The adduct 55 was obtained in 53% yield. The reaction of 30 and cyclohexenone 56 similarly gave the adduct 57 in 36% yield. In the case of dienone 58, however, the desired product could not be obtained. On the other hand, the Diels-Alder reaction with tranj-enone 59 afforded adduct 60 in a good yield (76% yield). Therefore, we felt confident that the reaction of benzocyclobutene 30 with enone (+)-31 would give the desired adduct with a tetracyclic skeleton. 

The ABCD ring system of the diterpene alkaloid atisine was constructed by T. Kametani et al using an intramolecular Diels-Alder cycloaddition reaction as the key step. The dienophile was obtained by the traditional Hofmann degradation of the corresponding dimethylamino precursor. The diene was prepared by the kinetic enolization of the cyclohexenone system with LDA. 

Diels-Alder reactions. This reagent is more reactive in Diels-Alder reactions than cyclohexenone. Treatment of the /i-nitro ketone with DBN effects elimination of HNO, to form the a,/ -enone.2 Thus the final products correspond to adducts of a cyclohexynone, but with reversed regioselectivity. 3-Nitro-2-cyclopentenone, m.p. 69-71°, is also a useful dienophile (second example). 

DIENOPHILES Acrolein. Ethynyl p-tolyl sulfone. 3-Methylsulfonyl-2,5-dihydro-furane. 3-Nitro-2-cyclohexenone. Phenyl vinyl sulfone. 

The three-step procedure above illustrates the usefulness of a 1-amino-3-siloxy diene for the synthesis of functionalized cyclohexenones and is representative of the general usefulness of the dienes. The first step in the sequence, the Diels-Alder reaction between the parent aminosiloxy diene nd methyl acrylate, cleanly produces the cycloadduct as a mixture of endo and exo diastereomers. This diene also reacts with many other dienophiles and the results are summarized in Table I.3 The cycloadducts are generally obtained as mixtures of endo-exo diastereomers, except for the reactions with N-phenylmaleimide and methacrolein, which proceed with high endo selectivity, and with dimethyl maleate, which gives predominantly the exo adduct. 

The usefulness of aminosiloxy diene Diels-Alder chemistry to the preparation of different substituted cyclohexenones is demonstrated in Table 11.3 The functionality at the 4 and 5-positions of the cyclohexenones can be easily controlled by the substitution pattern in the dienophile. The differing endo-exo selectivity found in the initial cycloadducts does not impact the usefulness of this route to cyclohexenones, since the amino group is eliminated in the last step. Chiral versions of aminosiloxy dienes provide the opportunity for asymmetric synthesis. Indeed, the diphenylpyrrolidine-substituted diene allows the synthesis of a variety of cyclohexenones, with good to excellent ee s 2b The usefulness of aminosiloxy diene Diels-Alder reactions to natural product synthesis is exemplified through the stereocontrolled synthesis of the pentacyclic indole alkaloid tabersonine 2c... 

Kozmin and RawaP examined the reactions of chiral diene 309 with various dienophiles. Using this strategy, cyclohexenones were obtained with very high ee values (86-98%). Thus, the reaction of 309 with methacrolein (310) afforded adduct 311, which... 

Two groups have reported the synthesis of the pentaketide epoxyquinols which differ in the approach to the epoxide 5, oxidation and subsequent electrocyclisation of which generates a 2//-pyran. Various dimerisation modes in which the pyran acts as either diene or dienophile then yield the epoxyquinols <05JOC79, 05TL547>. The reaction of this epoxide and a related cyclohexenone with reactive dienophiles circumvented the dimerisation and the cascade reaction produced the endo DA products <05JOC79>. 

The catalyzed Diels-Alder reaction of nonauxiliary-controlled homodienophiles has received much less attention than the auxiliary-controlled one. Systematic studies of aluminum chloride catalyzed addition of acyclic dienes 2 to substituted cyclohexenones l4 and 7 s have been undertaken. The nature of the substituent exerts a strong influence on the steric course of the reaction addition of the diene taking place from the less hindered face of the dienophile, anti to the substituent. The effect is stronger for 5- than for 4-substituted cyclohexenones. For some adducts cisjtrans isomerization under these reaction conditions has been observed4,5. 

Diels-Alder reactions. Compounds that give an oxygen-stabilized allyl cation are super-dienophiles in the presence of LiClQ,.OEt2. The method obviates the difficulties experienced with the low reactivities of 2-cyclohexenones. An intramolecular variant serves to construct tricyclic ketones expediently. 

The procedure for oxidation of the sulfide to the sulfone is based on that reported earlier by Bordwell and Pitt. The synthetic utility of phenyl vinyl sulfone and sulfoxide derives not only from their ability to serve as excellent Michael acceptors toward such reagents as enolate anions and organometallics, but also as moderately reactive dienophiles in Diels-Alder reactions. " The resulting adducts, in turn, can be chemically modified so that these electron-deficient olefins serve as useful synthons for acetylene,ethylene,terminal olefins,vinylsilanes, and ketene in [4 + 2] cycloadditions. Phenyl vinyl sulfone undergoes ready cycloaddition to Danishefsky s diene in the first step of a protocol for the regiospecific y-alkylation of 2-cyclohexenones. Furthermore, the ready lithiation of phenyl... 

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