Diels-Alder reaction boronic esters

The synthesis by K. C. Nicolaou and co-workers is summarized in Scheme 13.43. Diels-Alder reactions are prominent in forming the early intermediates. The formation of the A ring in steps A and B involves use of z-cli loroacrylonitrile as a ketene synthon. In step C, the pyrone ring serves as diene. This reaction is facilitated by phenylboronic acid, which brings the diene and dienophile together as a boronate ester, permitting an intramolecular reaction. 

An asymmetric aza-Diels-Alder reaction between functionalized 1,3-dienes and imines is mediated by a binaphthol-modified boronic ester (Scheme 108) (267). Unfortunately, at the present time the reaction requires a stoichiometric amount of the chiral promoter. 

Figure 15.16 Boronic ester annulation, including a Diels-Alder reaction, developed by Micalizio and Schreiber [47].

Most chiral organoboron Lewis acids reported to date are based on an organoborane that is attached to a chiral organic moiety such as a diol, aminoalcohol, or other readily available chiral substrates.Organoboron derivatives recently used as catalysts in enantioselective Diels-Alder reactions include the family of chiral acyloxyboranes (CAB) with (196) and (197) as representative examples and various cyclic boronic esters such as (198) and (199). An interesting system that combines the favorable Lewis acid properties of fluorinated arylboranes with a chiral Bronsted acid has been developed by Ishihara and Yamamoto. The Bronsted acid-assisted chiral Lewis acids (BLA) (200) was found to be highly effective in enantioselective cycloadditions of Q ,jS-enals with various dienes. The presence of the Bronsted acid functionality leads to significant acceleration of the reaction. 

Three successive [2+4] cycloadditions were used in the synthesis of the pentacyclic methyl ether of G-2N by Kraus and Zhao [92] and later, by a slightly modified procedure, also of the natural product G-2N (118) [93] (Scheme 31). Thermal reaction of the cyclobutanol 112 with acrylic ester gave the dihydronaphthalene 113 which was demethylated by treatment with boron tribromide and converted into the exocyclic ketene acetal 114. This unstable diene was reacted in a second cycloaddition with 2,6-dichlorobenzoquinone (115) to afford the tetracyclic chloroquinone 116. In a last Diels-Alder reaction, ring E was anella-ted by treatment of 116 with l-methoxy-l,3-bis[(trimethylsilyl)oxy]-l,3-buta-diene (117) to yield the pentacyclic natural product G-2N (118) [93]. 

Other Uses. Reagent 1 has been used for enantioselec-tive enolborination, albeit with poor (1.1 1) selectivity. Similar bis-sulfonamide-derived boron Lewis acids have been used for aldol additions, "" ester-Mannich reactions, Diels-Alder reactions, Ireland-Claisen reactions, and [2,3]-Wittig rearrangements. Similar bis-sulfonamide-derived aluminum Lewis acids have been used for aldol additions, Ehels-Alder... 

Chiral alkyldihaloboranes are among the most powerful chiral Lewis acids. In general, however, because alkyldihaloboranes readily decompose to alkanes or alkenes as a result of protonolysis or /3-hydride elimination, it is difficult to recover them quantitatively as alkylboronic acids. Aryldichloroborane is relatively more stable and can be reused as the corresponding boronic acid. We have developed chiral aryldichlorobor-anes 23 bearing binaphthyl skeletons with axial chirality as asymmetric catalysts for the Diels-Alder reaction of dienes and a,/3-unsaturated esters (see, e.g., Eq. 37) [36]. 

Erraan and Stonehave devised a new method for the construction of the tricyclic skeleton associated with such sesquiterpenes as a-patchoulene (438) and cyperene (439). The route they employed was the formation of the acid-ester (440 R = OH) by a Diels-Alder reaction of 3-ethoxycarbonyl-2,4-dimethyl-penta-1,3-diene with acrylic acid. The corresponding diazo-ketone (440 R = CHN2), on treatment with boron trifluoride etherate, gave the keto-esters (441) and (442) directly. This direct acid-catalysed cyclization proved to be more efficient than the conventional copper-catalysed thermal decomposition of (440 ... 

This method was used by Hudlicky in a synthesis of the alkaloid narciclasine. The diol 90 was trapped as the usual acetal and reacted as a diene with the nitroso ester Me02C-N0 in a hetero-Diels-Alder reaction to give 91. Suzuki coupling of the vinylic bromide with the right aryl boronic acid gave 92 and the N-0 bond was reduced with Mo(CO)6 to give the advanced intermediate 93 on the way to narciclasine28 94. 

Both enantiomers of binaphthol have found many uses as chiral reagents and catalysts. Thus, they modify reducing agents (e.g., lithium aluminum hydride) for the reduction of ketones to chiral secondary alcohols (Section D.2.3.3.2.) or react with aluminum, titanium or boron compounds to give chiral Lewis acids for asymmetric Diels-Alder reactions (Section D. 1.6.1.1.1.3.) and ene reactions (Section D.I.6.2.). They have also been used as chiral leaving groups in the rearrangement of allyl ethers (Section D.l.1.2.2.) and for the formation of chiral esters with a-oxo acids (Section D. 1.3.1.4.1, and many other purposes. 

There are many other enantiomericaUy pure boron-based Lewis acid catalysts used in the Diels-Alder reaction, Amongst these the dichloroborane (8.40) used by Hawkins is noteworthy because the substrates used were enoate esters, such as methyl acrylate (8.41) ° a, 3-unsaturated ketones and acid chlorides such as (8.42) rather than the enals generally tested in Diels-Alder reactions. 

Diels-Alder reactions. Vinyidichloroborane reacts with simple dienes in toluene at 110° to form adducts in good yield. These are isolated as the boronic esters of pinacol (equation I). Of greater interest, the C—B bond of the adduct can be replaced by... 

In order to prepare the cyclohexenaldehyde 8, 3-hydroxy-2-pyrone 14 and ethyl 4-hydroxy-2-methyl-2-butenoate 15 are subjected to a Diels-Alder reaction in the presence of phenylboronic acid which arranges both reactants to the mixed boro-nate ester 19 as a template to enable a more efficient intramolecular Diels-Alder reaction with optimal control of the regiochemical course of the reaction. Refluxing in benzene affords the tricyclic boronate 20 as primary product. This liberates the intermediate cycloadduct 21 upon transesterification with 2,2-dimethylpropane-l,3-diol which, on its part, relaxes to the lactone 22. Excessive i-butyldimethyl-silyltriflate (TBSTf) in dichloromethane with 2,6-lutidine and 4-7V,A-dimethyl-aminopyridine (DMAP) as acylation catalysts protects both OH goups so that the primary alcohol 23 is obtained by subsequent reduction with lithiumaluminum-hydride in ether. 

The chemists have long believed that the trivalent boron atom with its empty p orbital should behave in a fashion to that of the traditional organic electron-withdrawing group [1]. This idea is attractive when applied to the activation of Diels-Alder dienophiles, because the intermediate boron compounds can be transformed to an array of different functional moieties, none of which can usually be obtained by a direct Diels-Alder reaction. Matteson [2] and Evans [3] have reported the reactions of vinylboronic esters with dienes under strenuous reaction conditions but with low yields of the products. Similarly, vinyldichlo-roborane gives low yield [4] on reaction with cyclopentadiene. 

In this first example, a cobalt(I)-catalyzed Diels-Alder reaction employing alkynyl boron derivatives 2 and 1,3-diene 1 for preparation of dihydroaromatic building blocks 4 is disclosed. Ensuing, dihydroaromatic boronic ester intermediates 3 were used as useful synthetic scaffolds in an unusual thermal Diels-Alder reaction with different dienophiles, generating highly substituted and functionalized products in acceptable to very good yields by recrystallization after four synthetic steps. Five new C—C bonds from four simple components were formed in this process. 

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