Endo Products Research Articles

Asymmetric [4+2] cycloadditions employing 1,3-dienes derived from ( R)-4- t-butyldimethyl-silyloxy-2-cyclohexen-1-one

1,3-Dienes derived from ( R)-4- t-butyldimethylsilyloxy-2-cyclohexen-1-one react with activated dienophiles to form predominately (or sometimes exclusively) syn/ endo products. These controlled [4+2] cycloadditions increase the asymmetric complexity from one asymmetric center in the starting material to five asymmetric centers in the products in a single step, and provide a powerful approach for the asymmetric synthesis of compounds containing the bicyclo[2.2.2]octanone carbon skeleton.

Effect of Ring Size on theExo/EndoSelectivity of a Thermal Double Cycloaddition of Fused Pyran-2-ones

A study of an unusual effect of the size of the ring fused to 2H-pyran-2-ones on the exo/endo selectivity of a thermal double cycloaddition of N-substituted maleimides or maleic anhydride yielding bicyclo[2.2.2]octene derivatives is presented. With subtle variations of starting compounds and reaction conditions exclusively exo,exo or exo,endo products can be prepared.

Endo-selective enyne ring-closing metathesis promoted by stereogenic-at-Mo monoalkoxide and monoaryloxide complexes. Efficient synthesis of cyclic dienes not accessible through reactions with Ru carbenes.

Stereogenic-at-Mo monoalkoxide and monoaryloxide complexes promote enyne ring-closing metathesis (RCM) reactions, affording the corresponding endo products with high selectivity (typically >98:<2 endo:exo). All catalysts can be prepared and used in situ. Five-, six-, and seven-membered rings are obtained through reactions with enyne substrates that bear all-carbon tethers as well as those that contain heteroatom substituents. The newly developed catalytic protocols complement the related exo-selective Ru-catalyzed processes. In cases where Ru-based complexes deliver exo and endo products nondiscriminately, such as when tetrasubstituted cyclic alkenes are generated, Mo-catalyzed reactions afford the endo product exclusively. The efficiency of synthesis of N- and O-containing endo diene heterocycles can be improved significantly through structural modification of Mo catalysts. The modularity of Mo-based monopyrrolides is thus exploited in the identification of the most effective catalyst variants. Through alteration of O-based monodentate ligands, catalysts have been identified that promote enyne RCM with improved efficiency. The structural attributes of three Mo complexes are elucidated through X-ray crystallography. The first examples of catalytic enantioselective enyne RCM reactions are reported (up to 98:2 enantiomer ratio and >98% endo).

Asymmetric Construction of Nitrogen-Containing [2.2.2] Bicyclic Scaffolds Using N-(p-Dodecylphenylsulfonyl)-2-pyrrolidinecarboxamide

An organocatalyzed approach to enantioenriched isoquinuclidines and bicyclo[2.2.2]octanes via a p-dodecylphenylsulfonamide-modified proline catalyst has been developed. A series of aromatic imines have been explored for the formation of isoquinuclidines with high levels of enantioselectivity and diastereoselectivity, strongly favoring the exo product. A series of aliphatic imines has also been explored, which provide access to bicyclo[2.2.2]octanes through a novel mechanistic pathway in high levels of enantioselectivity and diastereoselectivity, favoring the endo product.

Comparison of stirred tank and airlift bioreactors in the production of polygalacturonases by Aspergillus oryzae

The production of endo and exo-polygalacturonase (PG) by Aspergillus oryzae IPT 301 was studied in a stirred tank bioreactor (STR) and an internal circulation airlift bioreactor. Using a factorial experimental design, a soluble culture medium was defined which allowed the production of exo- and endo-PG comparable to that obtained in a medium containing suspended wheat bran. The soluble medium was used in tests to compare the production of these enzymes in the STR and airlift bioreactor. In these tests, after 96 h, maximum enzymatic activity values achieved for exo- and endo-PG were 65.2 units (U) per mL and 91.3 U mL −1, in the STR, with similar activity values of 60.6 U mL −1 and 86.2 U mL −1, respectively, being achieved in the airlift bioreactor. The airlift bioreactor also showed satisfactory results regarding the oxygen transfer rate in this process, indicating its potential to be used in an eventual larger scale production of exo- and endo-PG, with lower costs for both installation and operation.

6- exo versus 7- endo iodolactonizations of 2-(alkynyl)phenylacetic acids

Exposure of 2-alkynylphenylacetic acids to excess iodine in acetonitrile containing anhydrous potassium carbonate delivers good yields, either of the corresponding isochroman-3-ones or benzo[ d]oxepin-2(1 H)-ones, depending upon the alkyne substituent: when this is alkyl, the former 6- exo products dominate, otherwise the 7- endo products are formed largely or, more often, exclusively.

Modular Total Synthesis of Lamellarin G Trimethyl Ether

A modular synthesis of the lamellarin G trimethyl ether has been developed based on the application of several reaction ­sequences which include Friedel-Crafts acylation, esterification, haloarylation, and oxidative cyclization. The formation of pyrrolo [2,1-a]isoquinoline core, the key step for the successful completion of lamellarin G trimethyl ether synthesis, is comfortably accomplished through the haloarylation of 3-bromo-4-(3,4-dimethoxy-benzoyl)-6,7-dimethoxy-chroman-2-one which has resulted in exclusive endo product.

Preparation of halo enol phostones by reaction of acetylenic phosphonate monoesters with (bis-collidine)halo hexafluorophosphate

Reaction of non-conjugated acetylenic phosphonate monoesters with (bis-collidine) bromo and iodo hexafluorophosphates was found to lead to the formation of halo enol phostones. Depending on the size of the heterocyclic compounds formed (6–8-membered compounds), endo or a mixture of endo and exo cyclization products were obtained.

Brønsted Acid Catalyzed Enantioselective 1,3-Dipolar Cycloaddition

An asymmetric 1,3-dipolar cyclo­addition of nitrones with ethyl vinyl ether catalyzed by chiral phosphoramides is reported. The presented reaction yields the endo products as the major diastereomer. Several phosphoramides bearing different aryl groups at the 3,3′-positions of the binol backbone were screened, with catalyst 1 giving the best results. A variety of diaryl nitrones could be employed in this reaction. High enantioselectivities were obtained only with electron-deficient aryl groups.

Enantioselective 1,3‐Dipolar Cycloaddition of Nitrones with Ethyl Vinyl Ether: The Difference between Brønsted and Lewis Acid Catalysis

Brønsted and Lewis face off: A new chiral N-triflyl phosphoramide is used for asymmetric 1,3-dipolar cycloaddition of diaryl nitrones to ethyl vinyl ether to give the endo products in up to 93 % ee (see scheme; Tf=trifluoromethanesulfonyl; Ad=adamantyl). The structure of the chiral phosphoramide was confirmed by X-ray crystallographic analysis. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z705314_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Hydrazide-catalyzed 1,3-dipolar nitrone cycloadditions

The triflate salts of cyclic hydrazides function as asymmetric catalysts for the [3+2]cycloadditions of nitrones with α,β-unsaturated aldehydes. The camphor-derived hydrazides show a preference for the exo isomers during these reactions, providing a compliment to other organically catalyzed dipolar cycloadditions. Enantiomeric excesses as high as 93% were realized for the exo isomers, while some endo products were obtained in 94% ee.

Enantioselective Rh-Catalyzed Intermolecular Hydroacylation

The authors report the first asymmetric rhodium-catalyzed intermolecular hydro­acylation reaction. It is found that monodentate phosphine ligands give endo products while bidentate phosphine give exo products selectively. Interestingly, even the minor exo isomers obtained from monodentate ligands are formed in consistently higher ee values than the corresponding endo isomers.

An Unprecedented Rhodium‐Catalyzed Asymmetric Intermolecular Hydroacylation Reaction with Salicylaldehydes

AbstractAn unprecedented enantio‐ and diastereoselective rhodium‐catalyzed intermolecular hydroacylation reaction of salicylaldehydes with norbornenes is reported in which the corresponding aryl ketones are obtained in high diastereomeric and moderate enantiomeric excesses. It was found that monodentate phosphoramidite ligands gave rise to endo products, while bidentate phosphine ligands catalyzed the reaction to form exo products predominantly.

The calculated effects of substitution on intramolecular cyclization of 2,5-hexadienyl radicals

The effects of substituents on the rate of intramolecular cyclization of the 2,5-hexadienyl radicals have been investigated computationally with DFT theory, using the UB3LYP functional. Various substituents – CN, NO 2, CH 3, NH 2, and t-butyl – at various positions – C 1, C 5 and C 6 – were considered in the calculations. An electron-donating substituent on the C 1 position raises the radical SOMO energies to increase the interaction with the alkene LUMO, whereas an electron-withdrawing counterpart lowers the SOMO and increases the interaction with the alkene HOMO. Both interactions decrease the activation energies, by 0.9–10.2 kcal/mol, and increase the rate of reaction rate, from 3 to 2.7 × 10 7 times. Similar results were obtained for the substituents at the C 6 position, and the activation energies for the intramolecular cyclization were decreased by 0.2–4.8 kcal/mol and the reaction rate increased from 2 to 2.8 × 10 3 times. The substituent at the C 5 position favors the formation of a 6- endo product because of a steric effect. The effects of disubstituents at both C 1 and C 6 positions were also investigated; the results showed that the electron-withdrawing groups decrease most effectively the activation energies. The so-called captodative effect was also investigated.

Intramolecular electrophilic hydroarylation via Claisen rearrangement: synthesis of chromenes, heterothiochromenes and heterodihydrothiochromenes

We have designed and synthesized several basic and novel fused ring heterocycles by intramolecular hydroarylation with an efficiency and scope to develop intermediates of potential value. This method demonstrated consistent performance with arene–ene and arene–yne substrates of diverse structural features, including propargyl ethers, allyl thioethers, and propargyl thioethers resulting in 6- endo products.

Synthesis of Complex Condensed Heterocycles by Diels-Alder Reactions

(E)-3-(2-Alkoxyvinyl)-benzofurans, -furopyridines and -indoles undergo rapid [4+2] cycloaddition reactions with even poorly reactive dienophiles under thermal and pressurized conditions to afford condensed dibenzofurans, dibenzofuro[2,3-c]pyridines, carbazoles, 2-azacyclopenta[c]fluorenes, furo[2,3-c]isochromenes, among other complex ring systems. Interesting temperature and pressure dependence on stereoselectivity was observed: endo products are derived by pressure-mediated reactions while exo isomers result under thermal conditions. For successful cycloaddition to give the [4.4.0] condensed isochromene and isoquinolinone systems, activated dienophiles such as maleic anhydride were required.

A New Method for Recycling Asymmetric Catalysts via Formation of Charge Transfer Complexes

[reaction: see text]. A new concept for recycling asymmetric bis(oxazoline)-type catalysts is reported. The formation of charge-transfer complexes between the chiral ligand and trinitrofluorenone and their subsequent precipitation and reuse by addition of new substrate solutions is described. The efficiency of this procedure is demonstrated in a Diels-Alder reaction to reach the expected endo product as major isomer (up to 97% de and 94% ee): the catalyst was used up to 12 times without loss of either activity or selectivity.

Diels–Alder Synthesis of endo-cis-N-Phenylbicyclo[2.2.2]oct-5-en-2,3-dicarboximide

endo-cis-N-Phenylbicyclo[2.2.2]oct-5-en-2,3-dicarboximide was synthesized by a Diels–Alder cycloaddition of 1,3-cyclohexadiene and N-phenylmaleimide in ethyl acetate. 1,3-Cyclohexadiene and N-phenylmaleimide were selected to illustrate the Alder rule, which reflects a preference for endo products and to overcome the difficulties associated with the traditional combination of 1,3-cyclopentadiene and maleic anhydride. This Diels–Alder reaction can be performed on macro- or miniscale, at room temperature for a week or under reflux for 2.5 hours to produce a 91% yield of a white solid that precipitates from solution and can be analyzed without further purification. Typical student results after 1.5 hours of reflux were 1.05 g (78%), mp 203.4–205.3 °C (lit. 204–206 °C). Results from IR and 1H and 13C NMR were consistent with literature values.

Salt, concentration, and temperature effects on an asparagine-based, aqueous Diels–Alder cycloaddition

Results are reported on the salt, concentration, and temperature effects in an aqueous, auxiliary-mediated asymmetric Diels–Alder cycloaddition. The auxiliaries were prepared under basic aqueous conditions from asparagine and trimethylacetaldehyde, and coupled to acryloyl chloride to generate dienophiles in one pot. Temperature and concentration modestly impacted cycloaddition stereochemistry. Experiments with a range of salts examined the speculation that complexation between the counterion of the auxiliary carboxylate and the dienophile carbonyl promotes the formation of the minor endo product, reducing cycloaddition diastereoselectivity for the endo products. The transformation was poorly selective for the carboxylic acid but gave moderate selectivities for several metallated carboxylates. The magnitude of the diastereoselectivity of the endo products was weakly dependent on carboxylate counterion and more strongly influenced by the basicity of the salt anion. Data presented suggest that Lewis acid catalysis reduces cycloaddition diastereoselectivity for the endo products.

Versatile Diastereoselectivity in Formal [3,3]-Sigmatropic Shifts of Substituted 1-Alkenyl-3-alkylidenecyclobutanols and Their Silyl Ethers

A new method for the preparation of highly substituted cyclohexenones is reported. [2 + 2] Cycloaddition of 2-silyloxydienes with allenecarboxylate affords the 1-alkenyl-3-alkylidenecyclobutanol silyl ethers. Thermolysis of these compounds affords the methylene cyclohexenyl silyl ethers with excellent exo selectivity (>95:5) when monosubstituted alkenyl groups are used, while the use of disubstituted alkenyl groups gives generally low selectivity ( approximately 2:1). However, rearrangement of the anion of the cyclobutanol (prepared by acidic hydrolysis of the TMS silyl ether) at low temperature gives the endo product with good to excellent diastereoselectivity (5-23:1). Two different mechanistic rationales are given for the two different processes: the first via a diradical and the second via a cleavage intramolecular Michael addition. Thus, the same starting material (e.g., 20) can be converted into either the exo or endo product, 22x or 22n, with good diastereocontrol by just changing the rearrangement conditions.