Asymmetric Diels-Alder cycloaddition

Racemic pyrone sulfoxide 52 undergoes a diastereoselective inverse-electron-demand 2 + 4-cycloaddition with 1,1-dimethoxyethylene to afford adduct 53 in > 95% yield (equation 49)100 this is the first example of an asymmetric Diels-Alder cycloaddition using a sulfinyldiene as an electron-deficient enophile101. 

High-pressure and thermally induced asymmetric Diels-Alder cycloadditions of heterosubstituted dienes to homochiral ot, -didehydro amino acid derivatives [82]... 

The asymmetric Diels-Alder cycloadditions of enantiopure (5)-5-(/ -tolylsulfinyl)-1,4-benzoquinones with Dane s diene under thermal and Lewis acid conditions produce tetracyclic quinones after spontaneous elimination of the sulfinyl group.The Diels-Alder reaction of barrelene with o-benzoquinone produces tetracyclo[6.2.2.2 .0 ]tetradeca-9,ll,13-triene-4,5-dione. Under kinetic control, the Diels-Alder cycloaddition of 2,3-dicyano-p-benzoquinone (98) with cyclopentadiene in MeOH produces the single cycloadduct (99) (Scheme 38). ... 

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... 

Evans DA, Chapman KT, Bisaha J (1984) New asymmetric Diels-Alder cycloaddition reactions. Chiral a,fS-unsaturated carboximides as practical chiral acrylate and crotonate dienophile synthons. J Am Chem Soc 106 4261-4263... 

Diels-Alder Cycloaddition Reactions. Catalysts 1 and 2 facilitate asymmetric Diels-Alder cycloaddition reactions between propenyl oxazolidinones (and thio-oxazolidinones) and dienes such as cyclopentadiene (eq 2). Both 1 and 2 display sim-... 

Catalytic asymmetric induction in Diels-Alder reactions is somewhat more difTicult to analyze based on these models. The chiral Lewis acids shown in Figure 43 all promote asymmetric Diels-Alder cycloaddition with variable degrees of enantioselectivity. " ... 

Jacobsen reported in 1990 that Mnm complexes of chiral salen ligands (41) were the most efficient catalysts available for the enantioselective epoxidation of alkyl- and aryl-substituted olefins.118 This stimulated a rapid development in the chemistry and applications of chiral SB complexes, which offer promising catalytic applications to several organic reactions, such as enantioselective cyclopropanation of styrenes, asymmetric aziridination of olefins, asymmetric Diels-Alder cycloaddition, and enantioselective ring opening of epoxides.4,119... 

Various types of chirally modified Lewis acids have been developed for asymmetric Diels-Alder cycloadditions. Some of these, including Ti-TADDOLates, have been attached to crosslinked polymers [11]. A recent example of this approach involved polymeric monoliths 103 containing TADDOL subunits (Scheme 3.29). The treatment of 103 with 71X4 afforded Ti-TADDOLates, which were used for the asymmetric Diels-Alder reachon of cyclopentadiene 104 and 105. The major product obtained in this reachon was the mdo adduct with 43% ee [58]. The supported Ti-catalysts showed an exhaordinary long-term stabihty, being achve for at least one year. 

The asymmetric Diels-Alder cycloadditions of 2-pyrones have recently attracted much attention. Albeit much remains to be explored, a few successful strategies have been reported, which have been systematically addressed in a recent review <99AC47>. 

Applications of chirally modified titanium Lewis acids have been reported most cases use various acetal diols derived from tartrate as the chiral auxiliary26 33,31 90. Various methods of catalyst preparation are known, as well as the use of different types of dienes (open-chained, cyclopentadiene) and dienophiles (acroleins, acrylates, crotonates, fumarates and amides derived from oxazolidinone), including intramolecular cycloaddition30. Addition of 4 A molecular sieves can improve asymmetric induction31,34 (as observed with the Sharpless epoxidation, loc. cit 31 in ref 6) and shows remarkable solvent effects on enantioselectivity. This method has been applied to the asymmetric Diels-Alder cycloaddition of cyclopentadiene and open-chain dienes to acrylamides28, 35. 

The asymmetric Diels-Alder cycloadditions of enantiopure (5)-5-(/ -tolylsulfinyl)-... 

Scheme 6.42. Camphor-derived auxiliaries for asymmetric Diels-Alder cycloadditions. (a,b) [170]. (cj [171]. The auxiliary illustrated in (a) is the enantiomer of that reported in ref. [170].

Even though the use of (S)-proline (1) for the synthesis of the Wieland-Miescher ketone, a transformation now known as the Hajos-Parrish-Eder-Sauer-Wiechert reaetion, was reported in the early 1970s, aminocatalysis - namely the catalysis promoted by the use of chiral second-aiy amines - was rediscovered only thirty years later. The renaissance of aminocatalysis was prompted by two independent reports by List et al. on the asymmetric intermolecular aldol addition catalysed by (S)-proline (1) and by MacMillan et al. on the asymmetric Diels-Alder cycloaddition catalj ed by a phenylalanine-derived imidazolidinone 2. These two reactions represented the archetypical examples of asymmetric carbonyl compound activation, via enamine (Figure ll.lA) and iminium-ion (Figure 11.IB), respectively. 

The first report concerning the synthesis of enantiomerically pure dienyl sulfoxides was made by Hoffmann and coworkers [32], who made use of the Horner-Wittig reaction between an a-phosphoryl sulfoxide and acrolein to give the corresponding dienyl sulfoxides as a mixture of geometric isomers. Recently, there has been considerable interest in the synthesis of 1-sulfinyl and 2-sulfinyl-l,3-butadienes, as these types of substrates have considerable potential as diene components in asymmetric Diels-Alder cycloadditions. 

Vinyl sulfoxides substituted at the p-position by electron-withdrawing groups have been used extensively as enantiomerically pme dienophiles in asymmetric Diels-Alder cycloadditions. Maignan and colleagues utilized methyl (Z)-(/ )-3-p-tolylsulfinyl propenoate (184), which reacted with cyclopentadiene under mild conditions high stereoselectivity and diastereoselectivity were observed [159] in formation of the endo and exo cycloadducts (185a) and (185b) (Scheme 5.60). 

Independently, Koizumi et al. also reported [160] the use of nonracemic 3-p-tolylsulfinylacrylates as dienophiles in highly diastereoselective Diels-Alder reactions. The functionalized bicyclo[2.2.1]heptane derivatives such as (186), obtained by asymmetric Diels-Alder cycloaddition of ethyl p-tolylsulfinylmethylenepropionate with cyclopentadiene, have been used as intermediates for the synthesis of bicyclic sesquiterpenes such as (+)-epi-P-santalene (187) [161,162] (Scheme 5.61). 

Carretero and colleagues have recently reported a systematic study on the use of enantiomerically pme 2-p-tolylsulfinylmaleates as dienophiles in asymmetric Diels-Alder cycloadditions with cyclopentadiene over a wide range of catalysed and uncatalysed conditions [164]. High diastereofacial selectivities were observed in some cases, and the stereochemical results have been interpreted using a sterically controlled approach. 

The trienamine-catalysed asymmetric Diels-Alder cycloaddition reaction of 2,4-dienals (77) with chiral phosphorous dienophiles (78) produced densely functionalized phosphonocyclohexene adducts (79) with excellent enantioselectivity (up to 99% ee) and good to high diastereoselectivity (up to >99 1) (Scheme 22). The thermal Diels-Alder reaction of l-phosphono-(3,4)-disubstituted-1,3-butadienes with maleimides and 4-phenyl-l,2,4-triazoline-3,5-dione produced polycyclic phosphonic acid derivatives. ... 

The stereoselective total synthesis of (-l-)-perophorami-dine 160 is an elegant example of an asymmetric Diels-Alder cycloaddition with a 1-azadiene (Scheme 41.33). This natural product has from origin Perophora namei asci-dia fungal cultures and displays cytotoxicity against the HCTl 16 colon carcinoma cell line. 

Me30+BF4 has also been used as a methylating agent of the lithium enolate of a (5-keto sulfoxide, leading to a mixture of isomeric dienol ethers, which are of potential interest as substrates for asymmetric Diels-Alder cycloadditions (eq 13). ... 

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