Synthesis and Diels-Alder reactions of 2-alkyl-5-methylene-1,3-dioxolan-4-ones and 2-alkyl-3-acyl-5-methylene-1,3-oxazolidin-4-ones: Highly exo and diastereoface selective chiral ketene equivalents

Chiral dienophiles 1–3 undergo highly exo and diastereoface selective Diels-Alder reactions. The Diels-Alder reactions of 3 are also highly exo selective under Lewis acid catalyzed conditions.     

Stereoselectivities of thermal and Lewis acid catalyzed intramolecular Diels-Alder reactions of internally activated dienophiles to form 5–11 membered rings

The thermal and Lewis acid catalyzed intramolecular Diels-Alder reactions of 1 (n = 5–11) have been studied. The catalyzed reactions efficiently form 7–11 membered rings and produce mainly cis adducts. Lewis acids prevent the five-membered ring forming reaction.     

Photochemically Catalyzed Diels-Alder Reaction of N-Arylimines with 2,3-Dihydrofuran and 3,4-Dihydro-2H-dihydropyran

Imino Diels-Alder reactions between N-arylimines and electron-rich dienophiles provide an easy entry into the tetrahydroquinoline derivatives. [1] This imino Diels-Alder reaction has been reported to be catalyzed by BF3· Et2O,FeCl3, InCl3 and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) etc.     

Direct organocatalytic asymmetric heterodomino reactions: the Knoevenagel/Diels-Alder/epimerization sequence for the highly diastereoselective synthesis of symmetrical and nonsymmetrical synthons of benzoannelated centropolyquinanes

Amino acids and amines have been used to catalyze three component hetero-domino Knoevenagel/Diels-Alder/epimerization reactions of readily available various precursor enones (1a-l), aldehydes (2a-p), and 1,3-indandione (3). The reaction provided excellent yields of highly substituted, symmetrical and nonsymmetrical spiro[cyclohexane-1,2'-indan]-1',3',4-triones (5) in a highly diastereoselective fashion with low to moderate enantioselectivity. The Knoevenagel condensation of arylaldehydes (2a-p) and 1,3-indandione (3) under organocatalysis provided arylidene-1,3-indandiones (17) in very good yields. We demonstrate for the first time amino acid- and amine-catalyzed epimerization reactions of trans-spiranes (6) to cis-spiranes (5). The mechanism of conversion of trans-spiranes (6) to cis-spiranes 5 was shown to proceed through a retro-Michael/Michael reaction rather than deprotonation/reprotonation by isolation of the morpholine enamine intermediate of cis-spirane (22). Prochiral cis-spiranes (5ab) and trans-spiranes (6ab) are excellent starting materials for the synthesis of benzoannelated centropolyquinanes. Under amino acid and amine catalysis, the topologically interesting dispirane 24 was prepared in moderate yields. Organocatalysis with pyrrolidine catalyzed a series of four reactions, namely the Michael/retro-Michael/Diels-Alder/epimerization reaction sequence to furnish cis-spirane 5ab in moderate yield from enone 1a and 1,3-indandione 3.     

Une etude perturbationnelle du role des catalyseurs dans les reactions de Diels-Alder

Catalyzed Diels-Alder reactions are examined by a simple perturbational treatment. Two hypotheses are made in the calculations: (1) the mechanisms of catalyzed and non-catalyzed Diels-Alder reactions are essentially the same, i.e., both are concerted, but not necessarily synchronous, frontier-controlled reactions; (2) the principal function of a Lewis acid in the reaction mixture is the complexation of a carbonyl or a nitrile groups by the catalyst. The agreement between theoretical predictions and experimental results is excellent.     

手性三齿席夫碱金属络合物催化的不对称反应*

各种手性三齿席夫碱与金属（钛, 铬, 钒, 铁, 铜, 铝）形成的络合物,在催化醛的硅腈化、Diels-Alder、Aldol、杂ene、硫化物的氧化等不对称反应中具有良好的催化活性和对映选择性;其中一些催化体系已成功的应用于天然产物的全合成中,该研究取得了系统性的研究成果。本文综述了手性三齿席夫碱金属络合物在不对称催化反应中的研究进展,同时,探讨了催化剂结构和反应条件对其催化活性和对映选择性的影响。     

Rhodium catalyzed tandem Diels-Alder/hydrolysis reactions of 2-boron-substituted 1,3-dienes

2-Boron substituted 1,3-dienes have been prepared and used in preliminary experiments to demonstrate that it is possible to effect rhodium catalyzed Diels-Alder/hydrolysis tandem reactions.     

Diastereoselective synthesis of the endo- and exo-spirotetronate subunits of the quartromicins. The first enantioselective Diels-Alder reaction of an acyclic (Z)-1,3-diene

[reaction: see text]. Diastereoselective syntheses of the endo- and exo-spirotetronates 1 and 2, corresponding to the galacto and agalacto fragments of quartromicins A3 and D3, are described. The key step of these syntheses are highly enantio- and diastereoselective Lewis acid catalyzed Diels-Alder reactions of the 1,1,3,4-tetrasubstituted diene 3.     

Development of efficient Lewis acid catalysts for intramolecular cycloaddition reactions of ester-tethered substrates

We have developed novel bidentate Lewis acids that efficiently promote the intramolecular cycloaddition reactions of ester-tethered substrates. Bis-aluminated triflic amide derivatives [TfN(AlR(1)R(2))2], which are generated by simply mixing triflic amide and 2 equiv of methyl aluminum or aluminum hydride, catalyzed intramolecular Diels-Alder (DA) reactions of ester-tethered 1,7,9-trienes and intermolecular DA reactions of alpha,beta-unsaturated lactones. We also found that bimetallic Lewis acid derived from 1,1'-biphenyl-2,2'-di(triflyl)amide and dimethylaluminum chloride promoted the intramolecular [3 + 2] cycloaddition reaction of acrylate derivatives having an allylsilane part.     

Asymmetric aza Diels-Alder reactions of amino acid ester imines with Brassard's diene

Imines 1 obtained from aromatic, aliphatic or functionalized aldehydes and valine tert-butyl ester undergo Lewis acid catalyzed hetero Diels-Alder reactions with Brassard's diene 2. The cycloadducts are formed in good to high yields and with diastereomer ratios of 92:8 – 97:3. For the removal of the chiral auxiliary group a new method was developed whose principle consists in the conversion of the amino acid -C-atom into an acetalic center employing a Curtius rearrangement as the key step.     

N-alkoxyacrylamides as substrates for enantioselective Diels-Alder reactions

[reaction: see text] The use of N-alkoxyacrylamides as substrates for Lewis acid catalyzed Diels-Alder reactions has been examined. Enantioselectivities up to 92% ee have been achieved using very simple chiral Lewis acids prepared from triisobutylaluminum and 2,2-dimethyl-alpha,alpha,alpha',alpha'-tetra-1-naphthalenyl-TADDOL (1-NaphtTADDOL). The use of Yamamoto's Zn-BINOL, easily prepared from Et2Zn and 1,1'-bi-2-naphthol (BINOL), proved to be even more efficient, and enantioselectivities up to 96% ee were achieved.     

Enantioselective Diels-Alder reactions with N-hydroxy-N-phenylacrylamide

[reaction: see text] The use of hydroxamic acids as templates for Lewis acid catalyzed enantioselective Diels-Alder reactions has been examined. A very simple chiral Lewis acid, prepared by mixing optically pure binaphthol with 3 equiv of trimethylaluminum, catalyzes the [4 + 2] cycloaddition of N-hydroxy-N-phenylacrylamide with cyclopentadiene at 0 degrees C in high yield (>96%) and with a fairly good level of enantioselectivity (91% ee). Facile conversion of the products to the corresponding alcohols or aldehydes makes the hydroxamic acid intermediates particularly useful.     

Endo-exo and facial stereoselectivity in the Diels-Alder reactions of 3-substituted cyclopropenes with butadiene

A computational examination of the four modes of addition in the Diels-Alder reactions of 3-substituted cyclopropene derivatives (substituents: BH(2), CH(3), SiH(3), NH(2), PH(2), OH, SH, F, and Cl) with butadiene have been carried out at the B3LYP/6-31++G(d)//HF/6-31++G(d) level. The degree of stabilization of these derivatives at the ground state correlates with the electronegativity of the substituent. This attenuation of reactivity and differences in steric interactions are the only factors needed to explain both the high facial selectivity and the differences in the endo-exo selectivity seen in these reactions. Furthermore, evidence is presented that indicates that stabilization by an interaction involving the syn C-3 hydrogen of cyclopropene and butadiene is small or irrelevant in controlling the endo-exo selectivity of the Diels-Alder reaction.     

Isolation and structure elucidation of three metabolites from verticillium intertextum: sorbicillin, dihydrosorbicillin and bisvertinoquinol

From the culture medium of Verticillium inlertexlum three metabolitcs have been isolated, namely the hexaketidcs sorbicillin (1) and 2'3'-dihydrosorbicillin (2), and the dimeric hexaketide bisvertinoquinol (3). 1 has previously been isolated from Penicillium chrysogenum and also synthesised. Hydrogenation of 1 yielded tetrahydrosorbicillin (8), 2'5'-dihydrosorbicillin (9) and 2',3'-dihydrosorbicillin (2). 2 was also obtained by a BF₃-catalysed condensation of 2,4-dimethyl-resorcinol (5) with (4R^*, 5S^*)-4,5-dibromo-hexanoic acid (6), followed by debromination with zinc and acetic acid. The structure of the dimeric hexaketide 3 (without absolute configuration) was obtained by X-ray structure analysis. It may be considered to be a Diels-Alder adduct of the quinols 11 and 12, the latter being related to 1 and 2, respectively, by simple hydroxylation at C(5). The ¹H and ¹³C NMR signals of 3 and its mono-methyl ether 10 are interpreted and compared with the corresponding properties of 1, 2, vertinolide (4), 3-methoxy-2-methyl-2-cyclohexenone (14), and 2-[(E,E)-2,4-hexadienoyl)]-cyclohexanone (13). The latter was prepared by acylation of the lithium enolate of cyclohexanone with sorbyl chloride. From the spectra of the hexaketides from V. intertextum several patterns have been extracted which are characteristic for some common and some distinguishing substructures in these natural products.     

Total synthesis of fully acetylated N-acetylneuraminic acid (Neu5Ac), 2-deoxy-beta-Neu5Ac, and 4-epi-2-deoxy-beta-Neu5Ac from D-glucose

Sialic acid and its analogues have been synthesized using a salenCo(II) complex catalyzed hetero Diels-Alder reaction and oxidative azidation (CAN/NaN3) of silyl enol ether as the key steps.     

Asymmetric Induction of Chiral 1,1''''-Bis(oxazolinyl)ferrocenes as Ligands in Metal-Catalyzed Cyclopropanation and Diels-Alder Reactions

Bis(oxazoline) ligands1 have been successfully used in a variety of metal-catalyzed asymmetric reactions, such as cyclopropanation, allylic oxidation reactions, etc; Chiral ferrocene derivatives2 have also been proved as effective ligands in numerous asymmetric reactions, for example, chiral ferrocenylphosphines exhibited high enantioselectivity for the reduction of olefins, Heck reactions and Aldol reactions of aldehydes. These results stimulated us to study the behaviour the bis(oxazoline) …     

Design, synthesis, and reactivity of 1-hydrazinodienes for use in organic synthesis

A new 1-hydrazinodiene (1) has been developed and utilized in Lewis acid catalyzed, intermolecular Diels-Alder reactions with various electron-deficient alkenes. The hydrazine can then be deprotected, and a molecule of methanesulfinic acid is eliminated to provide a putative diazene intermediate (4), which then spontaneously undergoes a suprafacial 1,5-sigmatropic shift to yield stereochemically complex cyclohexenes. This method has been applied to the synthesis of a constitutionally and stereochemically complex decalin derivative.     

The Efficient Preparation and Diels-Alder Reactions of 1,2-Bis[methylthio]-1, 3-Butadiene

The base catalyzed rearrangements of 1,4 bis-heteroatom substituted 3-butynes have been extensively studied by Brandsma, et al. ^2,3 Frequently, complex mixtures of products have been obtained. We wish to report an efficient, selective preparation of 1,2-bis(methylthio)-1, 3-butadiene 1 and its use in two Diels-Alder reactions.     

Asymmetric Diels-Alder reactions catalyzed by a triflic acid activated chiral oxazaborolidine

This paper reports a new method for the generation of chiral Lewis superacids by protonation of a non-Lewis acidic oxazaborolidine (1) with triflic acid. The resulting cationic species (3) are powerful and highly enantioselective catalysts for the Diels-Alder reaction of various 1,3-dienes with alpha,beta-enals. An optimization study (see Table 1) led to the selection of reaction conditions and catalysts (6A and 6B) which are very effective. The reactions are simple to conduct, reproducible, and economical, since only ca. 6 mol % of catalyst is required. In addition, the chiral catalyst precursor is readily recovered for reuse (>95% efficiency) and is commercially available. The broad scope of the process is documented by the 14 examples listed in Table 2. The absolute stereochemical course of the Diels-Alder reactions catalyzed by 6A and 6B was successfully predicted on the basis of the mechanistic principles which have recently been formulated for this type of catalytic enantioselective reaction involving re-face attack by the diene on complex 7. The mode of generation of Lewis superacids 6A and 6B allows an approximate comparison (or scale) connecting the catalytic power Lewis and protic acids.     

Silylium ion-catalyzed challenging Diels-Alder reactions: the danger of hidden proton catalysis with strong Lewis acids

The pronounced Lewis acidity of tricoordinate silicon cations brings about unusual reactivity in Lewis acid catalysis. The downside of catalysis with strong Lewis acids is, though, that these do have the potential to mediate the formation of protons by various mechanisms, and the thus released Br?nsted acid might even outcompete the Lewis acid as the true catalyst. That is an often ignored point. One way of eliminating a hidden proton-catalyzed pathway is to add a proton scavenger. The low-temperature Diels-Alder reactions catalyzed by our ferrocene-stabilized silicon cation are such a case where the possibility of proton catalysis must be meticulously examined. Addition of the common hindered base 2,6-di-tert-butylpyridine resulted, however, in slow decomposition along with formation of the corresponding pyridinium ion. Quantitative deprotonation of the silicon cation was observed with more basic (Mes)(3)P to yield the phosphonium ion. A deuterium-labeling experiment verified that the proton is abstracted from the ferrocene backbone. A reasonable mechanism of the proton formation is proposed on the basis of quantum-chemical calculations. This is, admittedly, a particular case but suggests that the use of proton scavengers must be carefully scrutinized, as proton formation might be provoked rather than prevented. Proton-catalyzed Diels-Alder reactions are not well-documented in the literature, and a representative survey employing TfOH is included here. The outcome of these catalyses is compared with our silylium ion-catalyzed Diels-Alder reactions, thereby clearly corroborating that hidden Br?nsted acid catalysis is not operating with our Lewis acid. Several simple-looking but challenging Diels-Alder reactions with exceptionally rare dienophile/enophile combinations are reported. Another indication is obtained from the chemoselectivity of the catalyses. The silylium ion-catalyzed Diels-Alder reaction is general with regard to the oxidation level of the α,β-unsaturated dienophile (carbonyl and carboxyl), whereas proton catalysis is limited to carbonyl compounds.