Diels-Alder cycloaddition to unsaturated

Horton, D, Koh, D, Takagi, Y, Stereocontrol in Diels-Alder cycloaddition to unsaturated sugars reactivities of cw-dienophiles with cyclopentadiene, Carbohydr. Res., 250, 261-274, 1993. 

HORTON ET AL. Diels—Alder Cycloaddition to Unsaturated Sugars... 

In 1968, Tobey and Law reported on the intriguing reaction of furan, substituted furans, and cyclopentadiene with both tetrachloro- and tetrabromocyclo-propene (TBCP). The two unsaturated systems reacted smoothly to directly produce cycloheptanoid systems, the products of a formal [4-i- 3]-cycloaddition reaction. The authors proposed in their early manuscripts that the tetrahalocy-clopropenes underwent an initial thermal Diels-Alder cycloaddition to produce the cyclopropyl norbornene derivatives la and lb (Figure 2). However, these workers were unable to isolate or characterize the primary cycloadducts and instead observed a product which had spontaneously rearranged by way of a halogen atom migration to yield the bicyclo[3.2.1]octadiene nucleus 2a and 2b. 

Diels-Alder cycloaddition of 3,4-bis(trifluoromethyl)furan with ethyl propynoate involved addition of two a,/3-unsaturated esters followed by acid-catalyzed ring opening, rearrangement, and elimination of ethanol to give a 6,7-bis(trifluoromethyl)isocoumarin-3-carboxylate [92JFC(56)359]. 

Anionic Diels-Alder reactions have been studied less extensively with the interest having been focused mainly on the cycloaddition of enolates of a,/l-unsaturated ketones with electron-poor olefins [24] (Equations 1.8 and 1.9). These reactions are fast and stereoselective and can be regarded as a sequential double Michael condensation, but a mechanism involving a Diels-Alder cycloaddition seems to be preferred [24b,f, 25]. 

The use of vinylallenes as the diene component in Diels-Alder reactions is very common, thus resulting in their ubiquitous use in natural product synthesis. A vinylal-lene has even been proposed by Schreiber and Kiessling [10] as a biogenetic intermediate in the synthesis of the skeleton of esperamicin A (32 —> 33). Their synthetic approach to esperamicin A (34) was modeled after this biogenetic proposal in which a Type II intramolecular Diels-Alder cycloaddition was used to gain access to the highly unsaturated bicyclic core of 34 (Scheme 19.8) [10]. 

Modifications to the architecture of the imidazolidinone catalyst provided the fnryl derivative (20) which proved to be a powerfnl catalyst for the catalytic asymmetric Diels-Alder cycloaddition of simple a,P-unsaturated ketones [50]. Although... 

An interesting expansion to the scope of dienes that could be adopted as partners within the Diels-Alder cycloaddition was reported by Deng (Scheme 57) [193]. Reaction of 3-hydroxypyrones 145 with a broad range of a,p-unsaturated ketones in the presence of the primary cinchona alkaloid 144 (5 mol%) provided the Diels-Alder adducts with exceptional levels of asymmetric induction (up to 99% ee). Within this report it was also shown that the related alkaloid 146 provided access to the enantiomeric adducts with similar levels of asymmetric induction. 

Both a,p-unsaturated iminium species and enals react with 4-hydroxypyran-2-ones to give pyrano[43-h]pyranones in a formal [3+3] cycloaddition (Scheme 24) <99JOC690>. In the presence of butadienes, the malononitrile derivative 42 obtained from a 3-hydroxypyran-4-one undergoes a one-pot sequential intramolecular [S+2] pyranone - alkene cycloaddition and a Diels-Alder reaction to give the O-bridged tricyclic system 43 (Scheme 25) <99JOC966>. 

The pioneer work on this subject using simple 1-azadienes is due to Ghosez et al. (82TL3261 85JHC69) they succeeded in reacting 1-azadienes as 47r-electron components in Diels-Alder cycloadditions. Thus, l-dimethylamino-3-methyl-l-azabuta-l,3-diene (a,/3-unsaturated hydrazone) 54 did undergo [4 + 2] cycloaddition to typical electron-poor dienophiles, e.g., methyl acrylate, dimethyl fumarate, acrylonitrile, maleic anhydride, and naphthoquinone, producing pyridine derivatives 55-57 (Scheme 14). 

The ability of related acylhydrazones 94 (Scheme 24), derived from a,/3-unsaturated aldehydes, to participate in intramolecular Diels-Alder cycloaddition reactions has been proven to occur by Gilchrist and coworkers (91TL125). They reported that azadiene 94 (n = 1) cyclized to 95, whereas compound 94 (n = 0) did not undergo intramolecular cycload-... 

Eberlin and Cooks578 discovered that acylium ions react with neutral isoprene and other 1,3-dienes in the gas phase to form covalently bound adducts by polar [4 + 2+] Diels-alder cycloadditions. The general reaction is given in Scheme 18, where R may range from H and alkyl to unsaturated, aromatic and polar substituents. The formation... 

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... 

The inter- and intramolecular Diels-Alder reactions of furans, and their applications to the synthesis of natural products as well as synthetic materials, were reviewed <1997T14179>. HfCU promoted the endo-seXccuve. inter-molecular Diels-Alder cycloadditions of furans with a,/3-unsaturated esters <2002AGE4079>. The cycloaddition between furan and methacrylate was also achieved under these conditions, providing, however the o-isomer as the major cycloadduct. A catalytic enantioselective Diels-Alder reaction between furan and acryloyl oxazolidinone to provide the < 46i-adduct in 97% ee was achieved by using the cationic bis(4-fer7-butyloxazoline)copper(ll) complex 55, as shown in Equation (41) <1997TL57>. 

Diels-Alder Reactions. Chiral a,p-unsaturated imides participate in Lewis acid-promoted Diels-Alder cycloaddition reactions to afford products in uniformly excellent endo/exo and endo diastereoselectivities (eq 50 and 51). Unfortunately, this reaction does not extend to certain dienophiles, including methacryloyl imides, p,3-dimethylacryloyl imides, or alkynic imides. Cycloadditions also occur with less reactive acyclic dienes with high diastereoselectivity (eq 52). Of the auxiliaries surveyed, the phenylalanine-derived oxazolidinones provided the highest diastereoselectivities. This methodology has been recently extended to complex intramolecular processes (eq 53). In this case, use of the unsubstituted achiral oxazolidinone favored the undesired diastereomer. 

Chiral Auxiliary for Asymmetric Induction. Numerous derivatives of (—)-8-phenylmenthol have been utilized for asymmetric induction studies. These include inter- and intramolecular Diels-Alder reactions, dihydroxylations, and intramolecular ene reactions of a,p-unsaturated 8-phenylmenthol esters. These reactions usually proceed in moderate to good yield with high diastereofacial selectivity. a-Keto esters of 8-phenylmenthol (see 8-Phenylmenthyl Pyruvate) have been used for asymmetric addition to the keto group, as well as for asymmetric [2 -F 2] photoadditions and nucleophilic alkylation. Ene reactions of a-imino esters of 8-phenylmenthol with alkenes provide a direct route to a-amino acids of high optical purity. Vinyl and butadienyl ethers of 8-phenylmenthol have been prepared and the diastereofacial selectivity of nitrone and Diels-Alder cycloadditions, respectively, have been evaluated. a-Anions of 8-phenylmenthol esters also show significant diastereofacial selectivity in aldol condensations and enantiose-lective alkene formation by reaction of achiral ketones with 8-phenylmenthyl phosphonoacetate gives de up to 90%. ... 

Diels-Alder cycloadditions occur on the endo face when the unsaturated bicyclic lactam is treated with 1,3-dienes such as Iso-prene (eq 10). Ester reduction followed by organolithium addition to the lactam carbonyl group and subsequent hydrolysis affords a variety of enantiopure functionalized cyclohexenes. ... 

Few examples of functionalization on the benzene ring of benzisothiazole have been reported (see Section 4.05.7.2). Studies on the reactivity of unsaturated chains in cycloaddition reactions have been reported (see Section 4.05.7.3). The high reactivity of 4-vinylisothiazolin-3-one A-oxides in Diels-Alder cycloadditions, both as diene and dienophile, is illustrated by their tendency to dimerize. 5-Vinylisothiazole A,A-dioxides react at the vinyl function with different 1,3-dipoles. Isothiazolo-3-sulfolenes 265 give an o-quinodimethane which can be trapped with a dienophile. Different isothiazole derivatives substituted with a carbon chain functionalized with heteroatoms have been prepared as ligands for the formation of complexes. 3-Oxocamphorsulfonimide reacts with the anion of alkynes and several studies on the reactivity of the products with electrophiles are reported. 

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