Stereoselectivity in Diels-Alder reaction

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

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. 

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. 

H.-J. Schneider, N. K. Sangwan, Diels-Alder reactions in hydrophobic cavities a quantitative correlation with solvophobicity and rate enhancements by macrocycles, J. Chem. Soc., Chem. Commun., 1986, 1787-1789 H.-J. Schneider, N. K. Sangwan, Changes of stereoselectivity in Diels-Alder reactions by hydrophobic solvent effects and by )S-cyclodextrin, Angew. Chem. Int. Ed. Engl, 1987, 26, 896-897. 

In Diels-Alder reactions a nitroolefin may function as an electron-deficient ene com-onent or a 1,2-dihydropyridine derivative may be used as a diene component. Both types of iactants often yield cyclic amine precursors in highly stereoselective manner (R.K. Hill, 1962 i. BOchi, 1965, 1966A). 

It has been established that alkoxy alkenylcarbene complexes participate as dienophiles in Diels-Alder reactions not only with higher rates but also with better regio- and stereoselectivities than the corresponding esters [95]. This is clearly illustrated in Scheme 51 for the reactions of an unsubstituted vinyl complex with isoprene. This complex reacts to completion at 25 °C in 3 h whereas the cycloaddition reaction of methyl acrylate with isoprene requires 7 months at the same temperature. The rate enhancement observed for this complex is comparable to that for the corresponding aluminium chloride-catalysed reactions of methyl acrylate and isoprene (Scheme 51). 

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>. 

Nitroalkenes with Chiral Auxiliaries The use of carbohydrates as chiral auxiliary in Diels-Alder reactions for the stereoselective preparation of carbocyclic and heterocyclic chiral rings is well documented.48 For example, D-manno-nitroalkene reacts with 2,3-dimethyl-1,3-butadiene to give a 65 35 mixture of adducts, as shown in Eq. 8.29. The configurations at C-4 and C-5 have been determined to be (4R,5R) and (45,55), respectively. Hydrolysis of the product followed by degradative oxidation of the sugar side chains leads to enantiomerically... 

In stereoselective reactions, Zn11 Lewis acids work well to achieve high selectivities (Scheme 54). Chiral complexes of Zn11 with chiral bis(oxazoline) ligands act as effective catalysts in Diels-Alder reactions of reactive dienes with dienophiles having bidentate chelating moieties such as... 

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. 

Stereospecificity, stereoselectivity and regioselectivity combined in Diels-Alder reactions give unprecedented control and you should now see why it is so important. The analgesic tilidine 47, effective in cases of severe pain, is an obvious Diels-Alder product.8 The regioselectivity is correctly ortho and the endo transition state 51 shows that the trans -enamine 49 is needed. This is the geometry we get when the enamine is made in the normal way from the enal 50 and Me2NH. 

The reactivity of 47/-benzopyran-4-ones in Diels-Alder reactions is well documented <1987T3075>, and recently high asymmetric induction has been achieved in the reaction of 3-alkoxycarbonyl-substituted chromones with chiral auxiliaries and Danishefsky s diene <1991JOC2058>. It should be noted that 3-formylchromones can react as heterodienes in the stereoselective inverse electron Diels-Alder reaction with enol ethers <1994T11755> to provide a route to pyrano[4,3-A][l]benzopyrans a heterocyclic nucleus which occurs naturally in the fungal metabolite fulvic acid <1984CC1565>. The thermal Diels-Alder reaction of 477-pyran-4-one 405 in the presence of an excess of Danishefsky s diene 404 provided cycloadduct 406 (Equation 32) <1996H(43)745>. 

Stereoselectivity is also observed in Diels-Alder reactions of dienophiles, which contain a stereogenic C=C double bond (Figure 15.15). A cis,trans-pair of such dienophiles, moreover,... 

Despite the low reactivity and poor stereoselectivity of compound 1 as a di-enophile, the main interest of the Maignan and Raphael s paper [5] derives from the fact that it was the first one involving the use of enantiomerically pure sulfoxides in Diels-Alder reaction, which would be used profusely later in asymmetric synthesis. For this reason it deserves some additional comments. From Scheme 2 can be deduced a moderate endo orientating character of the sulfinyl group [endo-adducts are the major ones (66%) in the mixture]. Although no explanation about the stereochemical behavior of compound 1 was offered in... 

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. 

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 an extension of this work, we have shown that 1,3-dienylborates including compounds (19), (20), (21) are exceptionally reactive and stereoselective dienes, far more reactive than dienylboronates (15) in Diels-Alder reactions 25. Interestingly, the reaction could be carried out in aqueous medium in some cases and led to the adducts (22), (23), (24) (figure 11). 

A number of thiocaibonyl compounds in the carboxylic acid oxidation state have been utilized in Diels-Alder reactions, but no systematic study in this area has been done. Some of the various structural types of thiocarbonyls which are reactive dienophiles are indicated in equations (90), (91) and (92).16s Reactions of this class show good to moderate regioselectivity, but relatively little is loiown with regard to stereoselectivity. Additional examples can be found in earlier reviews. ... 

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]. 

Acetylallene (1) behaves as an excellent dienophile in Diels-Alder reactions and induces peculiar orienting effects, allowing reactions with high regio- and stereoselectivities.2 Retro Diels-Alder reactions of modified adducts of furan and 1 afford a general method of synthesis of cc-functionalized ailenes.3... 

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