Endo diastereoselectivity

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 exo-endo diastereoselectivity is affected by Lewis acid catalysts, and the ratio of two stereoisomers can be explained on the basis of the FMO theory [17e, 46]. 

Good yields and high diastereoselectivities were obtained by using zeolites in combination with Lewis-acid catalyst [21]. Table 4.7 illustrates some examples of Diels-Alder reactions of cyclopentadiene, cyclohexadiene and furan with methyl acrylate. Na-Y and Ce-Y zeolites gave excellent results for the cycloadditions of carbocyclic dienes, and combining these zeolites with anhydrous ZnBr2 further enhanced the endo diastereoselectivity of the reaction. An exception is the cycloaddition of furan that occurred considerably faster and with better yield, in comparison with the classic procedure [22], when performed in the presence of sole zeolites. 

As expected, other enol ethers work well in these procedures. For example, Jones and Selenski find that implementation of method F, which occurs by addition of MeMgBr to benzaldehyde 5 in the presence of dihydropyran (DHP) at 78 °C affords a 66% yield of the corresponding tricyclic ketal 59 with better than 50 1 endo diastereoselectivity (Fig. 4.31).27 On the contrary, Lindsey reports use of method H with the benzyl alcohol 35 and diethylketene acetal. The cycloaddition reaction occurs almost instantaneously upon deprotonation of the benzyl alcohol 35 by f-butyl-magnesium bromide in the presence of the ketene acetal and yields the corresponding benzopyran ortho ester 60 in a 67% yield.29... 

According to recent quantum mechanical calculations, die importance of secondary orbital interactions, which have also been frequently used to explain die endo diastereoselectivity of Diels-Alder reactions, seems to be questionable and to be reserved for special cases like the addition of cyclopropene to various dienes. T. Karcher, W. Sicking, J. Sauer and R. Sustmann, Tetrahedron Lett., 33, 8027 (1992) R. Sustmann and W. Sicking, Tetrahedron, 48, 10293 (1992) Y. Apeloig and E. Matzner,./. Am. Chem. Soc., 117, 5375 (1995). 

A review of intramolecular 4 + 3-cycloadditions of allyl cations has been presented.277 The 4 + 3-cycloaddition reaction of C(2)-substituted furans with 1,3-dimethyloxyallyl cations show high endo diastereoselectivity and a cis dia-stereospecificity.278 The tandem Peterson olefination/[4 + 3]-cycloaddition of tertiary alcohols (149) in the presence of filran and Lewis acids (TiCLt) furnishes cycloheptanes (150) in modest yields (Scheme 57).279 (Trimethylsilyl)methyl allylic sulfones (151) were used to investigate the scope and limitations of intramolecular 4 + 3-cycloadditions of allylic sulfones (Scheme 58).280 Lewis acid-catalysed 4 + 3-... 

The reaction of 2- and 3-vinylindoles with dienophile 214 constitutes the first example of an asymmetric Diels-Alder reaction of vinyl heterocycles. From 3-vinylindoles, enantiomerically pure carbazoles 215a-c were obtained, whereas from the vinylindole 197 together with 215d, diastereomer 216 was obtained as a minor product. Conversely, 2-vinylindoles provided inseparable mixtures of diasteromeric carbazoles. On the other hand, the cycloaddition reactions of 3-vinylindoles with 217 furnish the tetrahy-drocarbazoles 218 with endo-diastereoselectivity (93T2863). 

Diels-Alder reaction of 2-bromoacrolein and cyclopentadiene using 10 mol% of titanium catalyst 74 gave the synthetically versatile (R)-bromoaldehyde adduct 75 in 94% yield, 67 1 exo. endo diastereoselectivity, and 93% ee. The absolute stereochemical outcome of the reaction is consistent with the proposed transition state assembly 76 in which the dienophile coordinates at the axial site of the metal, proximal to the indane moiety through Ji-attractive interactions. In this complex, the 7t-basic indole and the Ji-acidic dienophile can assume a parallel orientation facilitated by the octahedral geometry of the transition metal. The aldehyde would then react through a preferential s-cis conformation (Scheme 17.27).54... 

Powell, Maki, and Fu reported a Ni-catalyzed tandem radical 5-exo cyclization/ Stille coupling reaction (Fig. 19) [75]. When allylic bromo ethers 80 were subjected to a reaction with trichlorophenylstannane 81a in the presence of 10 mol% NiCl2 and 15 mol% of bipy 26, bicyclic phenyl-substituted products 82 were isolated in 57-67% yield and moderate to excellent endo-diastereoselectivity. Suzuki-Miyaura-type coupling reactions of 80 with arylboronic acids 81b worked similarly in 69-87%... 

Diels-Alder Reactions. Chiral a,p-unsaturated imides participate in Lewis acid-promoted Diels-Alder cycloaddition reactions to afford products in uniformly excellent endo/exo and endo diastereoselectivities (eq 50 and 51). Unfortunately, this reaction does not extend to certain dienophiles, including methacryloyl imides, p,3-dimethylacryloyl imides, or alkynic imides. Cycloadditions also occur with less reactive acyclic dienes with high diastereoselectivity (eq 52). Of the auxiliaries surveyed, the phenylalanine-derived oxazolidinones provided the highest diastereoselectivities. This methodology has been recently extended to complex intramolecular processes (eq 53). In this case, use of the unsubstituted achiral oxazolidinone favored the undesired diastereomer. 

The chiral tartrate-derived dioxaborolidine has been used to effect the enantiose-lective Diels-Alder reaction between a-bromoacrolein and cyclopentadiene [24]. In the presence of 20 mol % catalyst, the (2f )-bromoaldehyde is obtained in 96 % yield, 85 15 R S) enantioselectivity and 96 4 exo.endo) diastereoselectivity (Eq. 24). 

Besides being essentially 100 % stereospecific, the reaction of trans,trans-2,4-hexadiene with 1,3-cyclohexadiene is at least 98 % endo diastereoselective (Scheme 19) [39, 47, 48],... 

Scheme 19. endo Diastereoselectivity of the cation radical Diels-Alder. 

Keywords Stereogenic reactions. Mechanism control. Substrate and reagent control. Stereoselectivity, Simple diastereoselectivity, exo-endo-Diastereoselectivity, Double stereodifferentiation, Chiral catalysts, Chiraphor and catalaphor. Hybrid catalysts. Chiral auxiliary... 

H. E. Zimmerman. Thus triplet excited 4,4-diphenylcyclohex-2-en-l-one gives the phenyl migration product 5,6-bicyclo[3.1.0]hexan-2-one in high trans (or endo) diastereoselectivity (> 250 1). A different pathway (named Type A rearrangement) was found for cyclohexadienones (obviously directly connected with the di-7t-methane rearrangement) ... 

The generally observed endo preference has been justified by secondary orbital interactions, [17e, 42,43] by inductive or charge-transfer interactions [44] and by the geometrical overlap relationship of the n orbitals at the primary centers [45], The exo-endo diastereoselectivity is affected by Lewis acid catalysts, and the ratio of two stereoisomers can be explained on the basis of the FMO theory [17e, 46]. 

Cycloaddition reactions of the simple alkyl and aryl aldehydes 65 with (E)-l-methoxy- 1,3-butadiene (18b) under high pressure conditions afforded adducts 66 and 67 in reasonable to good yields [2g, 23]. A marked preference for the endo-diastereoselectivity has been observed as usual, applying pressure enforces endo-addition (Scheme 5.5). Using mild Lewis-acid catalysts [24], such as Eu(fod)3, Yb(fod)3, or Eu(hfc)3, in combination with pressure, allows good results to be obtained with the added advantage of reducing the pressure to lOkbar [25] (Scheme 5.5). 

Nitrone configuration is related to the problem of exo/endo diastereoselection. 

Compound 232 gave exo cycloadducts, along with smaller amount of the endo isomer in reaction with both dienes. Reactions of 233 with diphenylisobenzofuran led exclusively to the exo-isomers, in contrast to the endo diastereoselectivity observed for nonfluorinated a,p-unsaturated carbonyl compounds. 

The synthesis of seven-membered rings from furans and a,a -dibromoketones via oxyallyl intermediates is well known. It was reported that this reaction occurs quite easily when water is used as solvent <97TL8031>. In a study on the influence of steric and electronic effects on a function attached at C-2 of furans in the yield and diastereoselectivity of [4 + 3] cycloaddition reactions with oxyallyl cations it was found that in almost all cases a c/x-diastereospecificity and a high endo diastereoselectivity is obtained <97T11669>. A tandem Peterson olefination-[4 + 3] cycloaddition reaction with furans has been reported <97JOC1578 97TL386l>. For an intramolecular [4 -t- 3] cycloaddition see <97JOC6051>. The first asymmetric [4 + 3]... 

Hashimoto and coworkers [69] have recently begun to explore the use of chiral rhodium catalysts in the intramolecular dipolar cycloadditirai reactions of indoles, and have applied their methodology to the synthesis of the Aspidosperma ring system. Thus, the cycloaddition of the cyclopropyl carbonyl ylides derived from cyclopropyl diazo-5-imido-3-ketoesters 135 upon treatment with dirhodium (11) tetrakis[Af-tetrachlorophthaloyl-(5)-ferf-leucinate] gave cycloadducts 136 along with the spiro[2.3]hexanes 137 in only moderate yields (Scheme 34). Although the reaction proceeds with exclusive endo diastereoselectivity, only moderate enantioselectivities of up to 66% enantiomeric excess (ee) could be obtained. 

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