Diels-Alder reactions anthrones

Chiral bicyclic guanidine (221) has been identified as an excellent catalyst for reactions between anthrones (219) and various dienophiles, such as (220). The catalyst can tolerate a range of substituents and substitution patterns, making several anthrone derivatives suitable for this reaction. Both Diels-Alder and Michael adducts were obtained in excellent yields, high regioselectivities, and high enantioselectivities (<99% ee). This is the first case of a highly enantioselective base-catalysed anthrone Diels-Alder reaction.263... 

The first evidence of an anionic Diels Alder reaction was given by Rickborn [25a]. The reaction of anthrone with N-methylmaleimide in CHCI3 or THE occurs with low yield [26] (Equation 1.10), while in DMF or in the presence of catalytic amounts of amine (EtsN, Py) the reaction is completed in a few minutes [25]. 

Recently, Tan reported related bicyclic guanidine 20 as a chiral Br0nsted base to promote the highly enantioselective Diels-Alder reaction of various anthrones and maleimides (Scheme 5.41) [75]. Interestingly, use of dithranol led to the exclusive formation of the enantio-enriched Michael adducts. 

The reactivity and selectivity of cycloaddition can be considerably increased in intramolecular versions. The protocol was first demonstrated in the Diels-Alder reaction between anthrone 253416,417 and 4-hydroxy-2-butenoate mediated by phenylboronic acid (Equation (73)).418,419 Another method developed for the intramolecular cycloaddition is the synthesis of trienylboranes 256 by hydroboration of terminal alkynes (Equation (74)).419-422... 

Scheme 5.16 Diels-Alder reaction between anthrone and N-methyl maleidimide.

The use of a boron atom as a covalent template for intramolecularizing the Diels-Alder reaction has been relatively little investigated [20-22]. However Narasaka et al. have reported the use of a boronate template to control regio- and stereoselectivity in an IMDA reaction between anthrone 50 and methyl 4-hydroxybut-2-enoate 3 [20a]. Formation of the boronate tether was achieved by simply heating an equimolar mixture of phenylboronic acid with the diene and dienophile at reflux in pyridine with azeotropic removal of water. After 5 h, a single cycloadduct 51 was obtained in 81% yield. The tether was readily removed oxidatively affording the corresponding diol 52 in excellent yield (Scheme 10-19). 

An inspiring example of the bifunctional nature of prolinol compounds as catalysts suitable for cycloaddition reaetions has been disclosed by Kagan, who reported the Diels-Alder reaction of Af-methyl maleimide and anthrone catalysed by prolinol Ic (Scheme 7.13). The product was isolated in excellent yield and with 43% ee. An improvement of the stereocontrol was achieved when using Cj-symmetrie bis(hydroxymethyl) pyrrolidine 7... 

Metal-free bisoxazolines catalyzed Diels-Alder reaction of A-substituted maleim-ides 137 with anthrone 136 derivatives was achieved by Gbbel, et al. Scheme 3.45 [61]. With the photoelectron spectra and other studies, the Br0nsted-base catalysis is assumed to be involved with formation of an ion pair between the protonated catalyst 138 and the anthrone enolate, acting as diene. 

In 2008, Gobel et al. reported the Diels-Alder reaction of TV-substituted maleimides with anthrone derivatives which constituted the first asymmetric catalysis by a bisoxazoline in the absence of any metal ions. These cycloadditions led to the corresponding cycloadducts in excellent yields and moderate enantioselectivities (<70% ee), as shown in Scheme 6.9. 

Scheme 6.9 Diels-Alder reaction of Af-substituted maleimides with anthrone...

Simple chiral tertiary amines (90) have been shown to catalyse the Diels-Alder reaction of anthrone (88) and maleimides (89) to yield cycloadducts (91) in excellent yields (up to 96%) and enantioselectivities (up to 95% ee) (Scheme 26). The aminocat-alytic asymmetric ex -Diels-Alder reaction of a-methylene carbonyl dienophiles with 2,4-dienals formed chiral spirocycles in moderate to excellent diastereo- and enantio-selectivity. ... 

The first asymmetric chiral-base catalyzed Diels-Alder reaction of anthrone 79 with maleimide 80 was achieved by Kagan and Riant in 1989 [4]. With the use of quinidine (81) as catalyst, the cycloadduct 83a can be obtained in 97% yield with 61% ee (Scheme 38.23). The enantioselectivity was further improved to 87% by... 

More recently, Tan and coworkers successfully broadened the substrate scope and improved the enantioselectivihes for the Diels-Alder reactions of anthrones by utilizing new chiral bicyclic guanidine 84 as catalyst (Figure 38.3) [35]. Notably,... 

Figure 38.3 Chiral guanidine or thiourea catalysts for Diels-Alder reactions of anthrones (Scheme 38.23).

The cycloaddition is ascribable to the oxyanion of hydrogen-bonded enolate (ArO —HNEt3 ) rather than to the hydrogen-bonded enol (ArOH—NEtj). An enantioselective version of the reaction was achieved by using a homochiral amine [27]. Similarly the reactions with less reactive dienophiles such as dimethyl fumarate, fumaronitrile, maleonitrile and methyl acrylate give the Diels-Alder adducts quantitatively when the cycloadditions are carried out in THF or CHCI3 in the presence of EtjN, while in MeOH Michael adducts were isolated. Experimental evidence supports the hypothesis that the base-catalyzed cycloadditions of anthrone with dienophiles are concerted Diels-Alder processes [25b]. 

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