Stereoselective reactions Diels-Alder reaction

Aqueous cycloaddition using glyco-organic substrates. Facial stereoselectivity in Diels-Alder reactions of a chiral diene derived from D-glyceraldehyde [102]... 

Wada E., Yasuoka H., Pei W., Chin U., Kanemasa S. Lewis Add-Catalyzed Stereoselective Hetero Diels-Alder Reactions of (E)-l-Phenylsulfonyl-3-Alken-2-Ones With Vinyl Ethers. Synthetically Equivalent to Stereoselective Michael Type... 

Highly stereoselective hetero Diels-Alder reactions of a chiral liirylaldehyde (22) with Danishefiky s dioie were reported. In the presoice of Ln(OTf), exclusively 23 was obtained, while the reaction in the presence of Eu(thd)j produced 24 as the major product <96TA1199>. 

Actually one orientation predominates (called high regioselectivity) and only one diastereoisomer is produced (called high stereoselectivity). The Diels-Alder reaction is reversible and may be carried out under thermodynamic or kinetic controlled conditions. 

Another total synthesis of pamamycin-607 (lb) was reported in 2001 by our own group [6] at about the same time as the Lee synthesis. Here, the approach was based on the stereoselective intramolecular Diels-Alder reaction of vinyl-sulfonates and novel methods for elaboration of the resulting sultones [13,14]. 

Stereoselective intramolecular Diels-Alder reactions The reaction of Meldrum s acid (1) with (R)-citronellal (2) in the presence of ethylenediammonium acetate (EDDA)2 at 15-20° results in the tricyclic dihydropyran 3 as the major product with an optical purity of >98%. The product evidently results from an intramolecular hetero-Diels-Alder addition. It can be converted by acid into the optically pure a-methoxycarbonyllactone 4. 

Fig. 9. Nicolaou s asymmetric total synthesis stereoselective intramolecular Diels-Alder reaction.

The stereoselective intramolecular Diels-Alder reaction of 3-alkenyl(oxy)-2(l//)-pyrazinones leading to tricyclic ring systems was investigated <02TL447>. A one-pot 7-alkoxylation of 6-arylpyrazino[2,3-c][l,2,6]thiadiazine 2,2-dioxides 169 was accomplished by using N-halosuccinimides <02EJ02109>, and the nitration of 2-(5-methyl-2-furyl)quinoxaline was shown... 

A similar approach to the synthesis of tetracyclic indole alkaloid derivatives has been described [182], and the use of reactive chiral iminium ions allows the realisation of stereoselective aza Diels-Alder reactions even in aqueous solution [183,184]. Nevertheless it should be noted that reactions of electron-rich dienes with imines e. g. derived from amino acids do not necessarily proceed via a Diels-Alder mechanism. They may as well undergo a domino-Mannich-Michael sequence which also efficiently leads to useful nitrogen heterocycles [185-188]. 

Numerous further chiral imines activated by electron-withdrawing substituents have been investigated in order to carry out stereoselective aza Diels-Alder reactions. In these studies, Bailey et al. have recently introduced the use of two inducing stereocenters in the imine. This approach proved to yield excellent diastereoselectivities thus, imine 3-12 bearing a (,R)-8-phenylmenthyl auxiliary gave the essentially pure cycloadduct 3-13 upon hetero Diels-Alder reaction with cyclopentadiene (Fig. 3-4) [194-196]. 

As a current example of a stereoselective intramolecular Diels-Alder reaction using nitroso dienophiles, Kibayashi s studies aimed at the enantioselective total sysnthesis of (-)-pumiliotoxin C 4-31 shall be discussed here [356, 357]. The chiral nitroso compound 4-30 derived from L-malic acid was generated in situ... 

The Stereoselectivity of Diels-Alder Reactions. One of the most challenging stereochemical findings is Alder s endo rule for Diels-Alder reactions. The favoured transition structure 6.180 has the electron-withdrawing substituents in the more hindered environment, under the diene unit, giving the kinetically more favourable but thermodynamically less favourable adduct 6.181. Heating eventually equilibrates the adducts in favour of the exo adduct 6.182, by a retro-cycloaddition re-addition pathway. 

Evans et al. also showed that the 1 1 mixture of BAN and (3, y-distearoyl-phos-photidylcholine (DSPC) gives a smectic A texture in the temperature range of 57.3 to 100°C [21]. This is the first notice of lyotropic lamellar liquid crystals formed in the ionic medium. Additionally, Seddon et al. [28] and Neve et al. [29] have described the long-chained A-alkylpyridinium or l-methyl-3-alkylimidazolium ions to display smectic liquid-crystalline phases above their melting points, when Cl or tetrachloro-metal anions like CoCl " and CuCl " are used as the counter ions. Lin et al. have also noted the liquid crystal behavior of 1-alkylimidazolium salts and the effect on the stereoselectivity of Diels-Alder reactions [30]. However, liquid crystals are classified as ionic liquid crystals (ILCs), and they are distinguished from liquid crystals that are dispersed in ionic liquids. Although the formation of micelles and liquid crystal phases in ionic liquids have been thus reported, there has been no mention of the self-assembly of developed nano-assemblies that are stably dispersed in ionic liquids. In the next section the formation of bilayer membranes and vesicles in ionic liquids is discussed. 

SchneidCT, H.-J. Sangwan, N. K. Changes of stereoselectivity in Diels-Alder reactions by hydrophobic solvent effects and by p-cyclodextrin, Angew. Chem. Int. Ed. Engl 1987,26, 896-897. 

The key step to the tricyclic compound 17 seems to be the stereoselective aza Diels-Alder reaction (20) of the intermediate enamine dienophile 18 with azadiene adduct 19 to produce the imine complex 21. Allylboration of C=N bond in the latter proceeds also stereoselectively (21, arrow) furnishing the diborylated compound 22. 

In the course of a formal total synthesis of 3-deoxy-D-maimo-2-octulosonic acid (KDO), a chiral (salen)Co(II) complex was used to catalyze a highly double-stereoselective hetero-Diels-Alder reaction between an electron-rich chiral diene and ethyl glyoxylate (Sch. 56) [201]. This reaction was subsequently extended to achiral dienes [202]. 

Iron(III) 2-ethylhexanoate is a catalyst for the stereoselective hetero-Diels-Alder reaction of ethyl ( )-4-oxobutenoate with alkyl vinyl ethers to give ci5 -2-alkoxy-3,4-dihydro-2//-pyran-4-carboxylic acid ethyl esters with a high diastereoselectivity (Sch. 57) [203],... 

Hu, Y-J, Huang, X-D, Yao, Z-J, Wu, Y-L, Formal synthesis of 3-deoxy-D-manno-2-octulosonic acid (KDO) via a highly double stereoselective hetero-Diels-Alder reaction directed by a (salen)Co catalyst and chiral diene, J. Org. Chem., 63, 2456-2461, 1998. 

Berson, J.A., Hamlet, Z. and Mueller, W.A. (1962). The Correlation of Solvent Effects on the Stereoselectivities of Diels-Alder Reactions by Means of Linear Free Energy Relationships. A New Empirical Measure of Solvent Polarity. J.Am.Chem.Soc., 84,297-304. 

Baldoli, C., Maiorana, S., Licandro, E., Zinzalla, G., Lanfranchi, M., Tiripicchio, A. Stereoselective hetero Diels-Alder reactions of chiral tricarbonyl ( ti6-benzaldehyde)chromium complexes. Tetrahedron Asymmetry 200, 12, 2159-2167. 

Sosnovskikh, V. Y., Irgashev, R. A., Khalymbadzha, I. A. and Slepukhin, P. A. (2007) Stereoselective hetero-Diels-Alder reaction of 3-(trifluoroacetyl)chromones with cyclic enol ethers synthesis of 3-aroyl-2-(trifluoromethyl)pyridines with to-hydroxyalkyl groups. Tetrahedron Lett., 48, 6297-6300. 

Hajduch, J. Paleta, O. Kvicala, J. Haufe, G. Fluorinated furan-2(5H)ones reactivity and stereoselectivity in Diels-Alder reactions. Eur. J. Org. Chem. 2007, 5101-5111. 

Endolexo selectivity can be influenced by Lewis acids, the solvent or for example high pressure. The stereoselectivity of Diels-Alder reactions can be controlled and even altered by the appropriate use of chelating and non-chelating Lewis acids, too. Thus, by effective shielding of one of the enantiotopic faces of the diene or dienophile attached to... 

A highly stereoselective hetero Diels-Alder reaction of achiral N-acylimines with chiral enolethers derived from 8-phenylmenthol has been applied to the synthesis of the taxol side chain as outlined below. 

In 2008, a similar asymmetric Pictet-Spengler reaction was applied to the total synthesis of (+)-yohimbine (209) (11 steps, 14% overall yield), an important member of the monoterpenoid indole alkaloids as shown in Scheme 17.35 [82]. The synthesis involved two key steps, which are the acyl-Pictet-Spengler reaction of tryptamine derivative 199 with aldehyde 203 (97% ee) and a stereoselective intramolecular Diels-Alder reaction of 206 with the simultaneous generation of four new stereogenic centers [83]. 

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