Diels-Alder reactions boron

Bis(l,5-cyclooctadiene)nickel(0), 35 By Diels-Alder reaction Boron trifluoride etherate, 43... 

Chiral boron catalysts had already been widely used in a variety of reactions before they were applied in Diels-Alder reactions . Boron catalysts were first employed in the Diels-Alder reactions of quinones with electron-rich dienes. Kelly and coworkers found that stoichiometric amounts of a catalyst prepared from BH3, acetic acid and 3,3 -diphenyl-l.r-bi-2-naphthol (344) catalyzed the reaction of l-acetoxy-l,3-butadiene (341) with juglone (342) to afford cycloadduct 343 with 98% ee (equation 96). The reaction was supposed to proceed via a spirocyclic borate complex in which one face of the double bond of juglone was effectively shielded from attack by the diene. 

Van de Weghe disclosed an intramolecular hetero Diels-Alder reaction with an imino diene as part of a synthetic strategy for the synthesis of uncialamycin. In the key Diels-Alder reaction, boron trifluoride promotes the cycloaddition followed by DDQ-mediated oxidation to afford aromatic product 70. ... 

Chiral boron(III) Lewis acid catalysts have also been used for enantioselective cycloaddition reactions of carbonyl compounds [17]. The chiral acyloxylborane catalysts 9a-9d, which are also efficient catalysts for asymmetric Diels-Alder reactions [17, 18], can also catalyze highly enantioselective cycloaddition reactions of aldehydes with activated dienes. The arylboron catalysts 9b-9c which are air- and moisture-stable have been shown by Yamamoto et al. to induce excellent chiral induction in the cycloaddition reaction between, e.g., benzaldehyde and Danishefsky s dienes such as 2b with up to 95% yield and 97% ee of the cycloaddition product CIS-3b (Scheme 4.9) [17]. 

Scheeren et al. reported the first enantioselective metal-catalyzed 1,3-dipolar cycloaddition reaction of nitrones with alkenes in 1994 [26]. Their approach involved C,N-diphenylnitrone la and ketene acetals 2, in the presence of the amino acid-derived oxazaborolidinones 3 as the catalyst (Scheme 6.8). This type of boron catalyst has been used successfully for asymmetric Diels-Alder reactions [27, 28]. In this reaction the nitrone is activated, according to the inverse electron-demand, for a 1,3-dipolar cycloaddition with the electron-rich alkene. The reaction is thus controlled by the LUMO inone-HOMOaikene interaction. They found that coordination of the nitrone to the boron Lewis acid strongly accelerated the 1,3-dipolar cycloaddition reaction with ketene acetals. The reactions of la with 2a,b, catalyzed by 20 mol% of oxazaborolidinones such as 3a,b were carried out at -78 °C. In some reactions fair enantioselectivities were induced by the catalysts, thus, 4a was obtained with an optical purity of 74% ee, however, in a low yield. The reaction involving 2b gave the C-3, C-4-cis isomer 4b as the only diastereomer of the product with 62% ee. 

Yamamoto et al. have developed a catalytic enantioselective carbo-Diels-Alder reaction of acetylenic aldehydes 7 with dienes catalyzed by chiral boron complexes (Fig. 8.10) [23]. This carbo-Diels-Alder reaction proceeds with up to 95% ee and high yield of 8 using the BLA catalyst. The reaction was also investigated from a theoretical point of view using ab-initio calculations at a RHF/6-31G basis set. 

An expedient and stereoselective synthesis of bicyclic ketone 30 exemplifies the utility and elegance of Corey s new catalytic system (see Scheme 8). Reaction of the (R)-tryptophan-derived oxazaboro-lidine 42 (5 mol %), 5-(benzyloxymethyl)-l,3-cyclopentadiene 26, and 2-bromoacrolein (43) at -78 °C in methylene chloride gives, after eight hours, diastereomeric adducts 44 in a yield of 83 % (95 5 exo.endo diastereoselectivity 96 4 enantioselectivity for the exo isomer). After reaction, the /V-tosyltryptophan can be recovered for reuse. The basic premise is that oxazaborolidine 42 induces the Diels-Alder reaction between intermediates 26 and 43 to proceed through a transition state geometry that maximizes attractive donor-acceptor interactions. Coordination of the dienophile at the face of boron that is cis to the 3-indolylmethyl substituent is thus favored.19d f Treatment of the 95 5 mixture of exo/endo diastereo-mers with 5 mol % aqueous AgNC>3 selectively converts the minor, but more reactive, endo aldehyde diastereomer into water-soluble... 

The enantioselection depends greatly on the nature of the R2 group at the boron atom, and the ee values were as high as 97 %. High enantioselectivity was observed in the synthesis of 4-dihydropyranones, based on the Diels-Alder reactions of aldehydes 74 and Danishefsky s diene, catalyzed by a BINOL-Ti(0-i-Pr)4-derived catalyst [75] (Equation 3.23). 

Keywords chiral boron reagents, Diels-Alder reaction, stereoselective... 

Lewis acids such as zinc chloride, boron trifluoride, tin tetrachloride, aluminum chloride, methylaluminum dichloride, and diethylaluminum chloride catalyze Diels-Alder reactions.22 The catalytic effect is the result of coordination of the Lewis acid with the dienophile. The complexed dienophile is more electrophilic and more reactive toward electron-rich dienes. The mechanism of the addition is believed to be concerted and enhanced regio- and stereoselectivity is often observed.23... 

The Baccatin III synthesis by K. C. Nicolaou and co-workers is summarized in Scheme 13.54. Diels-Alder reactions are prominent in forming the early intermediates. In Step A the pyrone ring served as the diene. This reaction was facilitated by phenyl-boronic acid, which brings the diene and dienophile together as a boronate, permitting an intramolecular reaction. 

Recently, catalytic asymmetric Diels-Alder reactions have been investigated. Yamamoto reported a Bronsted-acid-assistcd chiral (BLA) Lewis acid, prepared from (R)-3-(2-hydroxy-3-phcnylphenyl)-2,2 -dihydroxy-1,1 -binaphthyl and 3,5A(trifluoromethy I) - be nzeneboronic acid, that is effective in catalyzing the enantioselective Diels-Alder reaction between a,(3-enals and various dienes.62 The interesting aspect is the role of water, THF, and MS 4A in the preparation of the catalyst (Eq. 12.19). To prevent the trimerization of the boronic acid during the preparation of the catalyst, the chiral triol and the boronic acid were mixed under aqueous conditions and then dried. Using the catalyst prepared in this manner, a 99% ee was obtained in the Diels-Alder reaction... 

Chiral Boron Catalysts for Diels-Alder reaction... 

Perhaps the most attractive method of introducing enantioselectivity into the Diels-Alder reaction is to use a chiral catalyst in the form of a Lewis acidic metal complex. In recent years, this area has shown the greatest progress, with the introduction of many excellent catalytic processes. Quite a number of ligand-metal combinations have been evaluated for their potential as chiral catalysts in Diels-Alder reactions. The most commonly used metals are boron, titanium, and aluminum. Copper, magnesium, and lanthanides have also been used in asymmetric catalytic Diels-Alder reactions. 

Stable aryl boronates derived from tartaric acid catalyze the reaction of cyclo-pentadiene with vinyl aldehyde with high selectivity. Chiral acyloxy borane (CAB), derived from tartaric acid, has proved to be a very powerful catalyst for the enantioselective Diels-Alder reaction and hetero Diels-Alder reaction. Scheme 5 23 presents an example of a CAB 73 (R = H) catalyzed Diels-Alder reaction of a-bromo-a,/i-cnal 74 with cyclopentadiene. The reaction product is another important intermediate for prostaglandin synthesis. In the presence of... 

Apart from its application in intermolecular Diels-Alder reactions, chiral acyloxy boron (CAB) can also be used to effect intramolecular Diels-Alder reactions with excellent stereoselectivity (Scheme 5-45).73... 

The second well-known and much-used carbon-carbon bond forming reaction is a [4 + 2]-cycloaddition, the Diels Alder reaction. Very many chiral Lewis acid catalysts have been used to promote this reaction and a pot-pourri of organo-aluminium, -boron and -copper catalysts are described, in brief, below. 

Oi and coworkers88 employed a cationic palladium(II) complex to catalyze Diels-Alder reactions. The benefits of such a catalyst compared to traditional catalysts such as boron and aluminum halides were reported to possess better stability to air and moisture,... 

Kunieda and colleagues155 used a similar kind of l,3-oxazolidin-2-one (234) and studied the diethylaluminum chloride and boron trifluoride etherate catalyzed Diels-Alder reactions of its A-acryloyl and A-crotonyl derivatives with cyclopentadiene. The yields were high (80-100%), the reactions being almost completely endo selective. The diastere-omeric excesses obtained ranged from 71% to more than 99%. 

Enyne 112a having a boron moiety on the alkyne gives vinyl boron 113a [Eq. (6.83)], whose carbon-boron bond can be converted to a carbon-carbon bond. Enyne metathesis followed by Diels-Alder reaction of the resulting diene with DMAD gives tricyclic compound 114 [Eq. (6.84)]. ... 

Recently, the first examples of catalytic enantioselective preparations of chiral a-substituted allylic boronates have appeared. Cyclic dihydropyranylboronate 76 (Fig. 6) is prepared in very high enantiomeric purity by an inverse electron-demand hetero-Diels-Alder reaction between 3-boronoacrolein pinacolate (87) and ethyl vinyl ether catalyzed by chiral Cr(lll) complex 88 (Eq. 64). The resulting boronate 76 adds stereoselectively to aldehydes to give 2-hydroxyalkyl dihydropyran products 90 in a one-pot process.The diastereoselectiv-ity of the addition is explained by invoking transition structure 89. Key to this process is the fact that the possible self-allylboration between 76 and 87 does not take place at room temperature. Several applications of this three-component reaction to the synthesis of complex natural products have been described (see section on Applications to the Synthesis of Natural Products ). 

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