Dienes hetero Diels-Alder cycloadditions

Lewis-acid-catalyzed asymmetric hetero-Diels-Alder cycloaddition of a 1-thiabuta-1,3-diene with chiral A/-acryloyl and A/-crotonyl oxazolidinone dienophile [105]... 

The first microwave-assisted hetero-Diels-Alder cycloaddition reaction was described by Diaz-Ortiz and co-workers in 1998 between 2-azadiene 198 and the same electron-poor dienophiles as for the preparation of pyrazolo[3,4-b]pyridines 200 (Scheme 72) [127]. These dienes reacted with... 

Another example, in which the piperidine cycle is generated de novo, exploits a hetero Diels-Alder cycloaddition of 1 -/r-tolylsulfinyl-1,3-penta-diene 91 with benzylnitrosoformate, that generates an oxazine 92 with complete regioselectivity and 7i-facial diastereoselectivity.69 Osmilation of the double bond inserts stereoselectively two hydroxyl groups on the oxazine skeleton, protection and catalytic hydrogenation finally afforded the enantiomerically pure imino sugars 94 (Fig. 38). 

The Lewis acid-mediated reactions of 2-aza-l,3-dienes and aldehydes, resulting in tetrahydro-l,3-oxazin-4-one derivatives, were explained in terms of the competitive existence of two reaction pathways a [4+2] hetero-Diels-Alder cycloaddition reaction and a Mukaiyama aldol reaction <2001TA439>. 

A 1-thiabuta-1,3-diene (104) undergoes highly stereoselective hetero-Diels-Alder cycloadditions with chiral A -acryloyloxazoIidinones.180... 

A further means of access to unsaturated carbohydrates from nonsugars is by application of the hetero-Diels Alder cycloaddition reaction between substituted-1,3-dienes (167) and aldehydes to give dihydropyrans (168). This... 

Dihydropyran-4-ones are formed with good enantiomeric excess by a chiral Lewis acid catalysed reaction of aldehydes with Danishefsky s diene and cyclisation of the initial aldol product. The overal process equates to a hetero-Diels-Alder cycloaddition (95JOC5998). Lactams also react with the electron rich diene under the influence of a Lewis acid, yielding 7-aza-l-oxaspiroalkenones (95JOC7724). 

H- and 13C-NMR spectra was possible on the basis of a two-dimensional hetero-nuclear chemical shift-correlated spectrum (78). Cleistopholine has been synthesized by a hetero-Diels-Alder cycloaddition of naphthoquinone and 1 -N,N-dimethylamino-1 -azapenta-1,3-diene (82). 

Total simple diastereoselectivity is observed in the hetero-Diels-Alder cycloaddition of nitro-soarencs to 1,3-dienes leading to the corresponding 3,6-dihydro-2//-l, 2-oxazines. A number of acyclic 1,4-disubstituted dienes have been reacted with nitrosoarenes, but the stereochemistry of the adduct 1 has not been assigned 6 s. 

Analogously to the oxidation of A -alkoxycarbonylhydroxylamines, the oxidation of A -hydrox-yureas, performed with tetraalkylammonium periodate, gives nitrosocarbonyl compounds which undergo hetero-Diels-Alder cycloaddition with 1,3-dienes. A number of adducts 10 have been prepared and the reaction proceeds with total diastereoselectivity, although the yield has only been reported for cyclopentadiene and Ar-hydroxy-A"-phenylurea33. 

The 1-amino-l,3-diene 1, which is readily prepared using literature procedures, undergoes regio- and stereoselective hetero-Diels- Alder cycloaddition with acylnitroso derivatives to give the 3,6-dihydro-2/f-2,3-oxazines 2. The yields are generally good and diastereomeric ratios vary as a function of both the dienophile s substituent and the temperature. The simple asymmetric induction is moderate112. 

Enders, D., Meyer, O. Diastereo- and enantioselective Diels-Alder reaction of 2-amino-1,3-dienes. Liebigs Annalen 1996, 1023-1035. Streith, J., Defoin, A. Aza sugar syntheses and multi-step cascade rearrangements via hetero Diels-Alder cycloadditions with nitroso dienophiles. Synlett 996, 189-200. 

Intramolecular versions of the ene reaction using Lewis acids can be applied to nonconjugated dienes. Thus, 2.8-dienoic acid derivatives lead to cyclohexane systems27. Side products in this conversion stem from intramolecular hetero-Diels-Alder cycloaddition. Chiral Lewis acids, such as titanium alkoxidcs modified with tartaric acid derived chiral diols, lead to asymmetric induction with up to 98% ee27,88. 

This reaction type has been applied to several other aldehydes and dienes and can be used in the synthesis of optically pure natural and non-natural carbohydrate-type systems, such as L-glucose. Hetero-Diels-Alder cycloadditions of this type can also be catalyzed by other chirally modified transition metal complexes, such as CpRu(CH2 = CH2)L3PF6 [L2 = (S)-Chi-raphos, (-)-Diop]68, (binaphthol)TiX269 70 102, vanadium103 104, or carbohydrate-modified titanium catalysts105. 

Asymmetric hetero-Diels-Alder cycloaddition of a diene with an aldehyde using the chiral catalyst 150 has been shown to proceed with very high levels of enantios-electivity, as illustrated in a key step of a synthesis of the natural product FR901464 (3.106). ° This catalyst is also effective for highly enantioselective hetero-Diels-Alder cycloadditions of a,(3-unsaturated aldehydes with ethyl vinyl ether. 

Hetero Diels-Alder cycloaddition reactions are of great importance in organic chemistry for the synthesis of six-membered heterocyclic ring systems. " In the past heterodienophiles and -dienes with one or more oxygen, nitrogen or sulfur atoms have been examined in thermal and Lewis acid-catalyzed reactions. " ... 

The Au(I)- or Ag(I)-catalysed intermolecular hetero-Diels—Alder cycloaddition of push-pull l,3-dien-5-ynes (76) with aldimines or silylaldimines (77) produced 5,6-dihydropyridin-2-ones (78) with high diastereo- and regio-selectivities (Scheme 24). A copper-catalysed intramolecular aza-Diels—Alder reaction has been used to produce dihydrochromeno[4,3-Mpyrrolo[3,2-/ quinolmes in good yields. The cinchonidine-derived quaternary ammonium catalyst, A-2, 3, 4 -trifluorobenzyl-0-benzylcinchonidinum bromide (79), catalysed the aza-Diels—Alder reactions between... 

Danishefsky s diene and imines to produce l,2-dialkyl-2,3-dihydro-4-pyridinones in high yields. Chiral non-racemic 2,5-diketopiperazine diene undergoes intermolecular hetero-Diels-Alder cycloaddition reactions with both c-rich and e-deficient alkene dienophiles, leading to bicyclo[2.2.2]diazaoctane structures. The regiochemical, stereoelectronic, and reactivity preferences of the diketopiperazine cycloadditions were investigated. ... 

Hetero-Diels-Alder Cycloaddition with Dienes. Under mild conditions, l,l -thiocarbonyldibenzotriazole readily reacts with cyclopentadiene to afford the hetero-Diels-Alder cycloadduct (4) (eq 2) in 98% yield. Analogous reaction with 2,3-dimethylbuta-diene, carried out under harsher conditions, was accompanied with elimination of a benzotriazole molecule to give benzotriazolyl-substituted thiopyran (5) (eq 3). ... 

The Diels-Alder reaction has not escaped the attention of chemists interested in asymmetric synthesis. A binaphthyl-based chiral aluminium complex (30) catalyses the hetero Diels-Alder cycloaddition between benzaldehyde and the Danishefsky diene (29), providing the dihydropyrone (32) with excellent selectivity after acid hydrolysis of the initial adduct (31). 0 2] (We will see further applications of chiral binaphthyl ligands in section 6.4.)... 

A review of the asymmetric thia-Diels-Alder reactions of chiral dithioesters with dienes has been published. The asymmetric organocatalytic thio-Diels-Alder reac- 0 tion of thiocarbonyls with a-methylene carbonyl dienes produced dihydrothiopyrans in high yields and high to excellent selectivities. The inverse-electron-demand 0 hetero-Diels-Alder cycloadditions of norbomene (106) with 5-benzylidene-2-arylimino-3-aryl-thiazolidine-4-thiones (107) at 25 °C produced cycloadducts (108)... 

The normal demand hetero Diels-Alder cycloaddition between nitroso reagents 171 and dienes 172 leads to the formation of 3,6-dihydro-1,2-oxazines 173 via the concomitant stereoselective formations of a C—N and a C O bonds (Scheme 41.36). Several nitroso dienophiles like the a-chloronitroso, arylnitroso, or acylnitroso compounds are known to react efficiently in cycloadditions. Chiral nonracemic chloronitroso and acylnitroso compounds have been developed to achieve diastereoselective nitroso Diels-Alder reactions, and recently Yamamoto and co-workers reported on the first enantioselective-catalyzed cycloaddition with a pyridylnitroso dienophile. ° ... 

Hetero-Diels-Alder cycloadditions of oxygen-substituted dienes have also been used for the construction of polyketide-derived natural products. This is exemplified in Danishefsky s synthesis of the zinc-sequestering ionophore zincophorin (213, Scheme 17.29) [111]. The MgBr2-mediated, chelate-con-... 

The classical Diels-Alder reaction is a cycloaddition between a conjugated diene and a second component, called dienophile, which has at least a n bond (Equation 1.1). When one or more heteroatoms are present in the diene and/or dienophile framework, the cycloaddition is called a hetero-Diels-Alder reaction. 

The hetero-Diels-Alder reaction can also employ dienes containing heteroatoms. Cycloaddition of substituted styrenes with di-(2-pyridyl)-1,2,4,5-tetrazine was investigated by Engberts (Eq. 12.56).127 Again, the rate of the reaction increased dramatically in water-rich media. Through kinetic studies, they showed that the solvent effects on the... 

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