(Z)-3-p-tolylsulfinylacrylonitrile as a chiral dienophile: diels-alder reactions with furan and acyclic dienes

The behavior of (Z)-3-p-tolylsulfinylacrylonitrile (1) as a chiral dienophile has been evaluated from its reactions with furan and acyclic dienes. Electrostatic interactions of the cyano group with the sulfinyl one restrict the conformational mobility around the C-S bond, thus controlling the pi-facial selectivity, which is almost complete in all cases, the approach of the diene from the less-hindered face of the dienophile (that bearing the lone electron pair) in the predominant rotamer being the favored one. The regioselectivity is also completely controlled by the cyano group. Additionally, the reactivity of compound 1 as well as its endo-selectivity are both higher than those observed for the corresponding (Z)-3-sulfinylacrylates, thus proving the potential of sulfinylnitriles as chiral dienophiles.     

Studies of Diastereoselectivity in Diels-Alder Reactions of Enantiopure (SS)-2-(p-Tolylsulfinyl)-1,4-naphthoquinone and Chiral Racemic Acyclic Dienes

Enantiopure sulfinylnaphthoquinone (+)-5 reacted with racemic acyclic dienes 1a-f bearing a stereogenic allylic center, through a tandem cycloaddition/pyrolytic sulfoxide elimination, to afford optically enriched compounds 8a-f and 9a-f with good like/unlike selectivities (ca. 75:25) and good enantiomeric excesses (68-82%), arising from the partial kinetic resolution of the racemic dienes. The opposite diastereoselection (8g-i: 9g-i, up to 5:95) was observed in reactions with dienes 1g-i, having an additional methyl group at C-3, the enantiomeric purities being moderate (14-25%). Steric effects and torsional interactions in the corresponding approaches account for the observed diastereoselectivities.     

Influence of the Sulfinyl Group on the Chemoselectivity and pi-Facial Selectivity of Diels-Alder Reactions of (S)-2-(p-Tolylsulfinyl)-1,4-benzoquinone

Diels-Alder reactions of (S)-2-(p-tolylsulfinyl)-1,4-benzoquinone (1a) with cyclic (cyclopentadiene and cyclohexadiene) and acyclic dienes (1-[(trimethylsilyl)oxy]-1,3-butadiene and trans-piperylene) under different thermal and Lewis acid conditions are reported. Chemoselectivity (reactions on C(2)-C(3) versus C(5)-C(6) double bonds) is mainly related to the cyclic (on C(5)-C(6)) or acyclic (on C(2)-C(3)) structure of the diene. The high pi-facial selectivity observed could be controlled by choosing adequate experimental conditions.     

Synthesis and dienophilic behavior of (S)-2-cyano-3-(p-tolylsulfinyl)-1,4- benzoquinone

Hydrocyanation of 2-(p-tolylsulfinyl)-1,4-benzoquinone (2) followed by oxidation with PhI(OAc)(2) gives 2-cyano-3-(p-tolylsulfinyl)-1,4-benzoquinone (1). The generation of 1 in the presence of cyclic and acyclic dienes affords the Diels-Alder adducts with a complete chemo- (only reaction with the sulfinyl-substituted double bond takes place), regio- (controlled by the cyano group), and endo selectivity (with respect to the quinone moiety), whereas the pi-facial selectivity is dependent on the structure of the diene.     

Palladium-catalyzed one-pot synthesis of polysubstituted furans from alkynoates and 2-yn-1-ols

Easily accessible propargyl vinyl ethers are found to be acyclic precursors to construct furan derivatives. According to the reactive behavior of the substrates and the regulation of reaction conditions, three synthetic routes to polysubstituted furans via palladium-catalyzed reactions of propargyl vinyl ethers in situ-prepared from alkynoates and 2-yn-1-ols are presented herein. These methods could have potential application in synthetic and pharmaceutical chemistry for its facilitation and accessible starting materials.     

Dual behavior of masked o-benzoquinones in intermolecular Diels-Alder reactions with acyclic dienes: a rapid entry to polyfunctionalized bicyclo[2.2.2]oct-5-en-2-ones and cis-decalins

The potentiality of the masked o-benzoquinones, i.e., 6,6-dimethoxy-2,4-cyclohexadienones 5-8, to react both as dienes and dienophiles in their intermolecular reactions has been demonstrated. The masked o-benzoquinones (MOBs) 5-8 generated in situ from 2-methoxyphenols 1-4 underwent intermolecular Diels-Alder cycloadditions with acyclic 1,3-dienes 9a-e to provide bicyclo[2.2.2]octenones 10a-f-13a-f along with cis-decalin derivatives 14a-f-17a-f with regio- and stereoselectivity, except in the case of MOB 8. The formation of cis-decalins in these Diels-Alder reactions illustrates the dienophilic character of MOBs, in addition to their general behavior as dienes. The ratio of the two cycloadducts obtained in each reaction as a result of the dual character of MOBs depends on the nature and/or position of the substituents on both the cyclohexadienone moiety and the added conjugated acyclic diene. All of the cycloadducts resulted from the diene property of MOBs in intermolecular Diels-Alder reactions smoothly underwent Cope rearrangement to furnish cis-decalins as sole products in excellent to quantitative yields.     

DFT study on the Diels-Alder cycloaddition between alkenyl-M(0) (M = Cr, W) carbene complexes and neutral 1,3-dienes

The thermal Diels-Alder reaction between alkenylmetal(0) Fischer carbenes and 1,3-dienes (isoprene and cyclopentadiene) has been studied computationally within the density functional theory framework. The selectivity of the [4 + 2] cycloadditions between alkenyl-group 6 (Fischer) carbene complexes and isoprene is similar to the selectivity computed for the reactions involving Lewis acid complexed acrylates. The experimentally observed complete endo selectivity in the [4 + 2] cycloadditions of alkenyl-group 6 (Fischer) carbene complexes with cyclopentadiene, which takes place under kinetic control, may be due in part to the presence of stabilizing secondary orbital interactions. These interactions are stronger than the analogues in the metal-free processes. The [4 + 2] cycloadditions between alkenyl-group 6 (Fischer) carbene complexes and neutral dienes occur concertedly via transition structures which are more asynchronous and less aromatic than their non-organometallic analogues, a behavior which is extensible to the reactions between Lewis acid complexed acrylates.     

Solvent Effect in Reaction of Singlet Oxygen with Conjugated Dienes

The 1,4-cycloaddition of singlet oxygen (¹O₂) to conjugated dienes provides a useful tool for simultaneous functionalization of the diene moiety, and its application to organic synthesis has been reported.¹ For the dienes bearing an allylic hydrogen, especially for the dienes not constrained to s-cis conformation, the 1,4-cycloaddition usually competes with the “ene” reaction as well as the 1,2-cycloaddition.² The efficiency of the oxygenation³ and the selectivity of the reaction modes are essential factors in the synthetic application. We have investigated the sensitized photooxygenation of representative acyclic dienes and vinylarenes i n various solvents.     

Exploring the intrinsic polar [4 + 2+] cycloaddition reactivity of gaseous carbosulfonium and carboxonium ions

Gas‐phase reactions of model carbosulfonium ions (CH₃‐S⁺ = CH_2; CH₃CH₂‐S⁺ = CH₂ and Ph‐S⁺ = CH₂) and an O‐analogue carboxonium ion (CH₃‐O⁺ = CH₂) with acyclic (isoprene, 1,3‐butadiene, methyl vinyl ketone) and cyclic (1,3‐cyclohexadiene, thiophene, furan) conjugated dienes were systematically investigated by pentaquadrupole mass spectrometry. As corroborated by B3LYP/6‐311 G(d,p) calculations, the carbosulfonium ions first react at large extents with the dienes forming adducts via simple addition. The nascent adducts, depending on their stability and internal energy, react further via two competitive channels: (1) in reactions with acyclic dienes via cyclization that yields formally [4 + 2⁺] cycloadducts, or (2) in reactions with the cyclic dienes via dissociation by HSR loss that yields methylenation (net CH⁺ transfer) products. In great contrast to its S‐analogues, CH₃‐O⁺ = CH₂ (as well as C₂H₅‐O⁺ = CH₂ and Ph‐O⁺ = CH₂ in reactions with isoprene) forms little or no adduct and proton transfer is the dominant reaction channel. Isomerization to more acidic protonated aldehydes in the course of reaction seems to be the most plausible cause of the contrasting reactivity of carboxonium ions. The CH₂ = CH‐O⁺ = CH₂ ion forms an abundant [4 + 2⁺] cycloadduct with isoprene, but similar to the behavior of such α,β‐unsaturated carboxonium ions in solution, seems to occur across the C = C bond. Copyright © 2012 John Wiley & Sons, Ltd.     

Asymmetric aza-Diels-Alder reactions of an N-tert-butanesulfinyl α-imino ester

Diastereoselective aza-Diels-Alder (aza-DA) reactions of an N-tert-butanesulfinyl α-imino ester with different dienes including activated and non-activated dienes in the presence of BF₃·OEt₂ are described. Diastereoselectivities up to 99% were observed for acyclic unactivated dienes. The absolute configurations of two aza-DA products have been solved by X-ray analysis.     

Racemic and asymmetric Diels-Alder reactions of 1-(2-oxazolidinon-3-yl)-3-siloxy-1,3-butadienes

Achiral and chiral 1-(2-oxazolidinon-3-yl)-3-siloxy-1,3-butadienes were prepared from readily available starting materials. Although more stable than the parent 1-amino-3-siloxy dienes, the 1-(2-oxazolidinon-3-yl)-3-siloxy-1,3-butadienes are still very reactive in Diels-Alder reactions, somewhat more than 1,3-dialkoxy-1, 3-butadienes (e.g., Danishefsky's diene). The cycloadditions of the achiral and chiral dienes with several different dienophiles were examined. The reactions proceeded in good yield, with modest to high endo selectivity. The chiral dienes exhibited excellent facial selectivity in cycloadditions with alpha-substituted acroleins, maleic anhydride and N-phenylmaleimide. Upon reduction and hydrolysis of the cycloadducts, substituted cyclohexenones were obtained with ee's ranging from 22% to >98%.     

2 + 4] and [4 + 2] cycloadditions of o-thioquinones with 1,3-dienes: a computational study

Cycloadditions of o-thioquinones (o-TQs) with 1,3-dienes could proceed via either a [2 + 4] or a [4 + 2] mechanism. Under kinetic control and with acyclic dienes the reaction affords the spiro cycloadducts 5deriving from the [2 + 4] path as the main products. Under thermodynamic control, or with cyclic dienes, the o-TQs behave as heterodienes to give the benzoxathiin derivatives 4, in most cases with complete regioselectivity. In the present computational study, DFT calculations were performed in order to achieve a deep understanding of both [2 + 4] and [4 + 2] paths. The reactions of three o-TQs with six 1,3-dienes were thoroughly investigated at the B3LYP/TZVP//B3LYP6-31G level, and the two reaction mechanisms were then compared, evidencing that [2 + 4] cycloadditions are kinetically favored, strongly asynchronous, or even unconcerted, while [4 + 2] reactions are thermodynamically favored, quite asynchronous, but undoubtedly concerted. Moreover, the observed regioselectivity was rationalized by mean of the FMO theory and by comparison of the activation energies for different pathways.     

自然轨道福井函数和成键活性描述符应用于解释苯硫醌和1, 3-二烯的[2+4]和[4+2]环加成反应中的成键机理

苯硫醌与脂肪族烯烃可以发生[2+4]和[4+2]环加成反应。为了解释这些环加成反应中的成键过程,本文使用了自然轨道福井函数(NOFF)与成键活性描述符。自然轨道福井函数揭示了苯硫醌和脂肪族烯烃的键或轨道的亲电性,表明电子供体的成键轨道和电子受体的反键/成键轨道之间发生了电子转移,然后成环,在这一过程中有两个共价键形成,得到了环状产物。成键活性描述符表明共价键比较容易在一个分子中具有较大f_k1⁺值的k1原子与另一个分子中具有较大f_k2^-值的k2原子之间形成。自然轨道福井函数与成键活性描述符都可以有效解释苯硫醌与1, 3-二烯之间的[2+4]与[4+2]环加成反应的机理。     

Catalytic enantioselective aza-Diels-alder reactions of imines--an approach to optically active nonproteinogenic alpha-amino acids

A catalytic enantioselective aza-Diels-Alder reaction of imines has been developed. The reaction of N-tosyl alpha-imino ester with different dienes including activated, non-activated, cyclic, and acyclic dienes has been investigated in the presence of various chiral Lewis acids. A series of phosphino-oxazoline ligands have been synthesized and evaluated for the reaction. It was found that the combination of phosphino-oxazoline ligands with copper(I) salts gives the best results for the activated dienes, while BINAP-copper(I) complexes are good catalysts for all the dienes studied. In the case of activated acyclic dienes the aza-Diels-Alder products can be obtained in higher than 80% isolated yield and 96% ee, while for the unactivated cyclic dienes the exo diastereomer is formed as the major product in up to 95 % ee. For an activated cyclic conjugated diene, 2-trimethylsilyloxy-1,3-cyclohexadiene, the reaction proceeds as a Mannich-type addition reaction giving optically active gamma-oxo alpha-amino acid derivatives in good yields and up to 96% ee. The reaction of an unactivated acyclic diene, 2,3-dimethyl-1,3-butadiene, with the N-tosyl alpha-imino ester gives both the aza-Diels-Alder and aza-ene products, in a ratio of 9:1 favoring the aza-Diels-Alder product. Furthermore, a series of different imines have been synthesized and investigated as possible substrates for the present catalytic enantioselective aza-Diels-Alder reaction in order to obtain mechanistic insight. All imines studied gave moderate to high ee. Particularly, the reaction of the N-phenyl and N-p-methoxyphenyl substituted glyoxylate imines with Danishefsky's diene proceeded well affording the corresponding aza-Diels-Alder product in high yield with up to 91% ee at room temperature. The present catalytic enantioselective reaction of imines provided an effective route to optically active nonproteinogenic alpha-amino acids. The products of the catalytic enantioselective aza-Diels-Alder reaction of the cyclic dienes can be used for the preparation of key compounds such as natural products and compounds of pharmaceutical interest. The absolute configurations of five products have been solved by X-ray structural analysis, and it is found that the absolute configuration of the aza-Diels-Alder adduct is dependent on the substituent on the imine nitrogen atom. It turned out that the N-tosyl glyoxylate imine and N-p-methoxyphenyl glyoxylate imine give the aza-Diels-Alder adduct with opposite absolute configuration using the same enantiomer of the catalyst. On the basis of the results the mechanistic aspects for the reactions are discussed.     

A facile synthesis of enantiopure tricyclic furanyl and pyranyl derivatives via tungsten-mediated cycloalkenation and Diels-Alder reaction

We report the synthesis of chiral furanyl and pyranyl dienes 1 and 2 based on cycloalkenation of chiral tungsten alkynol complexes. These two dienes bear a chiral 1,3-dioxolane group to control diastereoselective Diels-Alder reactions with electron-deficient olefins. The chiral 1,3-dioxolane substituents of the cycloadducts were degraded into hydrogen atoms to make these molecules possess common furan and pyran rings. Dienes 1 and 2 are good building blocks for enantiopure forms of tricyclic oxygen compounds.     

(NHC)NiH‐Catalyzed Intermolecular Regio‐ and Diastereoselective Cross‐Hydroalkenylation of Endocyclic Dienes with α‐Olefins

Highly selective cross‐hydroalkenylations of endocyclic 1,3‐dienes at the least substituted site with α‐olefins were achieved with a set of neutral (NHC)Ni^IIH(OTf) catalysts and cationic Ni^II catalysts with a novel NHC ligand. Under heteroatom assistance, skipped dienes were obtained in good yields, often from equal amounts of the two substrates and at a catalyst loading of 2–5 mol %. Rare 4,3‐product selectivity (i.e., with the H atom at C4 and the alkenyl group at C3 of the diene) was observed, which is different from the selectivity of known dimerizations of α‐olefins with both acyclic Co and Fe systems. The influence of the various substituents on the NHC, 1,3‐diene, and α‐olefin on the chemo‐, regio‐, and diastereoselectivity was studied. High levels of chirality transfer were observed with chiral cyclohexadiene derivatives.     

Asymmetric hetero-Diels-Alder reactions of N-sulfinyl dienophiles using chiral bis(oxazoline)-copper(II) and -zinc(II) triflates

Asymmetric hetero-Diels-Alder (HDA) reactions of N-sulfinyl dienophiles using bis(oxazoline)-copper(II) and -zinc(II) triflates are described. The cycloadditions with cyclic and acyclic 1,3-dienes have been studied. In most cases, good enantioselectivities (70-98% ee) and yields (60-85%) were obtained with stoichiometric amounts of the Lewis acids. Cyclic dienes gave the endo adducts as major products, while acyclic dienes provided cis adducts. The HDA adducts have been transformed into N-protected alpha-amino acid methyl esters, amino alcohols, and homoallylic amines. A stereochemical model, which accounts for the enantiofacial selectivity of the HDA reaction by a tetrahedral metal center, has been proposed. Mechanistic studies revealed positive nonlinear effects, assumed to arise from the formation of less-reactive heterochiral complexes. Investigation of the temperature dependence of the enantioselectivity indicated that at least two selective reaction steps exist in the zinc-catalyzed reaction. Reactions run with 10 mol % chiral Lewis acid gave poor yields and selectivities. However, in combination with TMSOTf (100 mol %), high yields (68-86%) and enantioselectivities (97-98% ee) were obtained.     

Second generation levoglucosenone-derived chiral auxiliaries. Scope and application in asymmetric Diels-Alder reactions

Chiral alcohols were designed and easily prepared from levoglucosenone, a biomass-derived valuable synthon. These alcohols were tested as chiral auxiliaries in asymmetric Diels-Alder reactions between the corresponding acrylates with acyclic and cyclic dienes. The regio, stereo, and facial selectivity varied from very good to excellent, depending upon the benzylic substitution of the auxiliary and the diene employed. As a consequence, after removal of the auxiliary, the resulting carboxylic acid derivatives were obtained in 72-99% ee.     

Reaction of diazoacetone,methyl diazoacetate,and dimethyl diazomalonate with 2-ethoxycarbonyl and 2-cyanofurans in the presence of rhodium acetate

Conclusions The reaction of 2-ethoxycarbonylfuran with diazoacetone and methyl diazoacetate in the presence of rhodium acetate at 20°C gives bicyclic adducts of the corresponding carbenes at a furan ring double bond in 18–22% yield with the complete absence of products of opening of the furan ring (acyclic oxodienes). In analogous reactions, 2-cyanofuran gives derivatives of 5-(2-furyl)oxazoles in yields up to 55%, which are the products of the 1,3-dipolar cyclo-addition of the carbenes at the cyano group in addition to the bicyclic adducts in 12–17% yields.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 12, pp. 2833–2836, December, 1988.     

Regio‐ and Stereochemical Studies on the Nitroso‐Diels–Alder Reaction with 1,2‐Disubstituted Dienes

The regioselectivity of the nitroso‐Diels–Alder reaction between unsymmetrical acyclic dienes and Boc‐nitroso (Boc=tert‐butoxycarbonyl) reagent or the Wightman chiral chloronitroso reagents has been studied. With the Boc‐nitroso reagent, the selectivity is a consequence of steric effects at the C1‐position in the diene and electronic effects at the C2‐position in the diene. The combination of an unprotected hydroxyethyl side chain at C1 and an electron‐withdrawing group at C2 allows complete regioselectivity in favour of the proximal isomer. The same isomer was obtained exclusively with the chiral nitroso reagent with high enantioselectivities. A model based on steric effects is proposed.