Exo-face selectivity

The Paterno-Buchi photocycloaddition between carbonyl compounds and furans was first described in 1965 (equation 6)80. This report noted that only the head-to-head product 171 was formed, and that high exo face selectivity was exhibited. Subsequent to this and other early reports, this reaction has been systematically explored by several groups, owing largely to the various ways in which the 2,7-dioxabicyclo[3.2.0]hept-3-ene ring system can be exploited730,81. 

The cycloaddition of 4-phenyl-3//-l,2,4-triazole-3,5(4//)-dione to 2-ex0-3-exo-bis(chloromethyl)-5-[( )-methoxymethylidene]-6-methylidene-7-oxabicyclo[2.2.1]heptane occurs exclusively, within the limit of detectability by H NMR, on the e.vo-face, i.e., from above the plane of the molecule, to give ll6. This is in contrast to the endo-face selectivity reported for a large number of cycloadditions of dienes grafted on to the bicyclo[2.2.1] skeleton (see also Section 7.2.10.3.1). The formation of 7-oxabicyclo[2.2.1]heptane-diazene charge transfer complexes, i.e., the assistance of the ethereal bridge in the cycloaddition, has been invoked to explain the exo-face selectivity. 

Furan adds to vinylene carbonate to produce an exolendo mixture of Diels-Alder adducts [165]. Double hydroxylation of the 7-oxanorbornene double bond is highly exo face selective (Scheme 13.88). The diol thus obtained is protected as an acetonide. Saponification of the carbonate liberates a mixture of diols that is oxidized into m 5 6>-l,5-anhydroallaric acid derivative 316. Treatment of 316 with AC2O generates the anhydride 317. Subsequent reaction of 317 with methanol gives racemic 318 that can be resolved by fractional crystallization with brucine or by chromatographic separation of the (7 )-l-((3-naphthyl)ethylamides. The individual isomers of 318 each react with ClCOOEt and Me3SiN3 in situ to provide enantiomerically pure d- and L-riboside derivatives [166]. 

Since e rfo-6-methyl-2-oxabicyclo[3.1.0]hex-3-ene (endo-20, R = Me) reacts with TCNE to give cxo-4-methyl-8-oxabicyclo[3.2.1]oct-2-ene-6,6,7,7-tetracarbonitrile (exo-21, R = Me) exclusively and the exo-epimer gives the endo-product exclusively, attack of TCNE has to be exo (face selectivity). This seems to be in contrast to the reaction of ex<7-6-methyl-2-oxabicyclo[3.1.0]hex-3-ene (24) with ( )- and (Z)-butenedinitrile and the addition of dimethyl butynedioate to dimethyl exo-2-azabicyclo[3.1.0]hex-3-ene-2,6-dicarboxylate (22), which show the reverse stereochemistry. However, in these cases, the reaction temperature is much higher and epimerization is fast compared to the cycloaddition. When the reaction is carried out under high pressure the cycloaddition is accelerated but there is little effect on the epimerization. At 70°C and 7x10 Pa, epimerization and cycloaddition are of a comparable rate and exo attack of ( )-butenedinitrile to en fo-6-methyl-2-oxabicyclo[3.1.0]hex-3-ene is observed to a large ex-... 

The monoaddition of bulky dienophiles such as ethylenetetracarboni-tirle (TCNE) to 10 are generally exo face selective (e.g., giving adduct 57). However, less bulky dienophiles such as butynone or methyl vinyl ketone prefer, for stereoelectronic reasons, to add onto the endo face of 10 giving monoadducts 58 and 59, respectively [201]. 

NMR spectra, all compounds 6-39-6-41 were formed as single diastereoisomers. The X-ray structure of 6-39c and 6-41d (Fig. 6.11) unambiguously revealed that nucleophiles attacked at the exo-face of the aziridine core in NSBV 6-1, probably because the exo-face is less hindered while the nucleophilic attack at the endo-face would be suffered from repulsion of bulky substituents at 3,7-positions on NSBV 6-1. This exo-face selectivity was also observed for the nucleophilic ring opening of SBV derivatives. 

Reaction with Fe2(CO)9 is exo face selective, giving a mixture of the corresponding mono complexes (7) (anti-exo) and (8) (sy/j-exo). Further complexation of (8) with Fe2(CO)9 occurs in a nonstereoselective fashion to give mixtures of the diiron com-... 

The diastereoselective intramolecular Michael addition of /(-substituted cyclohexcnoncs results in an attractive route to ra-octahydro-6//-indcn-6-ones. The stereogenic center in the -/-position of the enone dictates the face selectivity, whereas the trans selectivity at Cl, C7a is the result of an 6-exo-trig cyclization. c7.v-Octahydro-5//-inden-5-ones are formed as the sole product regardless of which base is used, e.g., potassium carbonate in ethanol or sodium hydride in THF, under thermodynamically controlled conditions139 14°. An application is found in the synthesis of gibberellic acid141. 

R2=C02CH3) exhibit little difference in face selectivity, i.e., syn selectivity when subject to NaBH symanti = 65 35 in 18d 62 38 in 18e) and DIBAL-H syn.anti = 66 34 in 18d 61 39 in 18e) reduction. The behavior of 18d and 18e is also consistent with orbital unsymmetrization, as in 19. On the other hand, Mehta et al. suggested the presence of significant electrostatic contributions from exo-electron-withdrawing groups, rationalizing the syn face selectivity in 18b [75]. 

Benzonitrile oxide, generated by dehydrochlorination of benzohydroximoyl chloride, undergoes regio- and face-selective cycloadditions to 6,8-dioxabicyclo [3.2.1]oct-3-ene 108a yielding a 4 1 mixture of 4,5-dihydroisoxazoles 109 and 110. Both products have exo-stereochemistry, resulting from the approach of the nitrile oxide from the face opposite to the the methyleneoxy bridge. Structures of the adducts were determined by 1 H NMR spectroscopy and, in the case of compound 109, by X-ray diffraction analysis (275). 

Alkylation of 5-oxo-pyrrolo[ l, 2-tjoxazole 279 proceeded selectively from the exo-face of the corresponding enolate when treated with a base and an electrophile such as RX. Depending on the reaction conditions and the base used, the ratio exojendo 280/281 varied from 63/37 to 98/2 (Equation 43) <1999TL2707>. 

Metal complexes of bis(oxazoline) ligands are excellent catalysts for the enantioselective Diels-Alder reaction of cyclopentadiene and 3-acryloyl-l,3-oxa-zolidin-2-one. This reaction was most commonly utilized for initial investigation of the catalytic system. The selectivity in this reaction can be twofold. Approach of the dienophile (in this case, 3-acryloyl-l,3-oxazolidin-2-one) can be from the endo or exo face and the orientation of the oxazolidinone ring can lead to formation of either enantiomer R or S) on each face. The ideal catalyst would offer control over both of these factors leading to reaction at exclusively one face (endo or exo) and yielding exclusively one enantiomer. Corey and co-workers first experimented with the use of bis(oxazoline)-metal complexes as catalysts in the Diels-Alder reaction between cyclopentadiene 68 and 3-acryloyl-l,3-oxazolidin-2-one 69 the results are summarized in Table 9.7 (Fig. 9.20). For this reaction, 10 mol% of various iron(III)-phe-box 6 complexes were utilized at a reaction temperature of —50 °C for 2-15 h. The yields of cycloadducts were 85%. The best selectivities were observed when iron(III) chloride was used as the metal source and the reaction was stirred at —50 °C for 15 h. Under these conditions the facial selectivity was determined to be 99 1 (endo/exo) with an endo ee of 84%. 

The chiral ir-allyl-Pd(II) intermediates shown in Scheme 84 undergo epimerization. The efficiency of this step and the regiochemistry of the nucleophilic attack to the exo face are very important for obtaining enantioface selection (Scheme 89). Bosnich analyzed the general characteristics of the asymmetric alkylation in terms of the properties of the allylic acetate substrates and of the 7T-allyl-Pd(II) intermediates, which undergo facile o-tc-o rearrangement, readily switching the face of Pd coordination (208). Examination of the dynamic equilibria of a series of cationic ir-allyl-Pd-chiral phosphine complexes has indicated that the 7r-allyl intermediates epimerize 10-100 times faster than the nucleo-... 

Because the norbomene double bond of dicyclopentadiene is more strained, its selective hydrofbrmyl-ation can be achieved under mild reaction conditions (entry 9). Under more vigorous reaction conditions both double bonds are hydroformylated. The exo faces of both rings are the least hindered, accounting for the selectivity. 

Selective reduction of 530 with DIBAL gave a mixture (1 3) of the allylic alcohols 531 and 532 via preferential delivery of hydride to the unsaturated carbonyl function from the exo face. The allylic alcohol 531 was then converted to the allylic ether 533 by reaction with diazomethane in the presence of anhydrous aluminum chloride, whereas the major allylic alcohol 532 was converted to... 

The photoreaction of 1-cyanonaphthalene with norbomadiene in benzene yields four kinds of (2 + 2) cycloadducts [134], The addition occurs exclusively on the exo face of norbomadiene. In more polar solvents, the reaction becomes more selective, favoring the exo face to the naphthalene ring at the 1,2-position. 

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