Enrfo-Selectivity

Mataka and coworkers further studied the exo/endo selectivity of outside attack products in the reactions of 96 and 97 with A-(5-X-phenyl)maleimides [56]. They found that the endo/exo selectivity is markedly dependent on the electronic nature of the substituent X (Scheme 47). The electro-withdrawing substituents such as NOj and Cl enhance enrfo-selectivity. The relative order of the enr/o-selectivity is NOj > Cl > H > OCH3. 

The Diels-Alder reaction is of wide scope. Not all the atoms involved in ring formation have to be carbon atoms the hetero-Diels-Alder reaction involving one or more heteroatom centers can be used for the synthesis of six-membered heterocycles. The reverse of the Diels-Alder reaction—the retro-Diels-Alder reaction —also is of interest as a synthetic method. Moreover and most importantly the usefulness of the Diels-Alder reaction is based on its yyn-stereospecificity, with respect to the dienophile as well as the diene, and its predictable regio-and enrfo-selectivities. °... 

The carbon acid Tf2CH2 reacts with Me3Al to form Me2AlCHTf2, which is an excellent catalyst for the highly enrfo-selective Diels-Alder reaction between cyclopentadiene and conjugated lactones. ... 

Edman and Simmons [146] synthesized bicyclo[2.2.1]hepta-2,5-diene-2,3-dicar-boxylic anhydride 80 as a facially perturbed dienophile on the basis of the norbornadiene motif, and its top selectivity in Diels-Alder reactions with cyclopentadiene (top-exo top-endo = 60 70 1) was observed by Bartlett (Fig. 14) [147], The most preferred addition was top-exo addition, along with the minor addition modes, top-endo bottom-enrfo addition (Fig. 14). The addition of butadiene to this anhydride preferentially afforded the top-adduct (top bottom = 6 1). In the addition of anthracene, a top-adduct was formed exclusively. 

Despite the mechanistic obscurity of C-H bond oxidation by chromic acid, regio-selectivity has been discerned in well defined systems [256]. For example, oxidation of enrfo-fenchyl acetate and the bomyl acetates (exo and endo) gives ketones in which the new carbonyl group is derived from a donor carbon. 

The origin(s) for the preference of stereostructure A in the acrylic acid ester addition is not known with certainty. A steric effect may explain the observation. The bulky acceptor substituent of the dienophile might be less hindered—and this is quite counterintuitive—in the enrfo-orientation in the transition state shown in Figure 15.31 than in the alternative exo-position. One might use the structure B to suggest that the substituent of the dienophile in A does not try to avoid the C atoms C2 and C3 as much as it tries to stay away from the H atoms cis-H1 and cis-H4. The increase of e/w/o-selectivity upon addition of a Lewis acid could then be explained by the premise that the complexing Lewis acid renders the ester group more bulky. This increased steric demand enhances its desire to avoid the steric hindrance in its ew-posi-tion. 

Fig. S Selectivity-reactivity relationship, p vs. log A plots, for solvolyses of a,a-dialkylbenzyl OPNB in 80% aqueous acetone at 25 C plots of ,a-dialkylbenzyl-OPNB carrying dialkyl groups structurally unspecified, otherwise specified O, benzyl-OPNBs squares denote 2-norbomyl derivatives, exo- and enrfo-isomers , benzyl-OPNBs having conjugative a-substituents.

A different distribution was observed when a-deutero-enrfo-armilenol was treated with similar reagents. This four-fold random distribution of deuterium, only among a, y, 5 and 0 carbons is consistent with [458] or rearranging [457]. Only four-fold randomization was observed when selectively a-deuterated [460] was transformed into the cation [457] (or [458]) by fluorosulfuric acid. Thus it necessarily follows that the 11-fold automerization is not a property of the armilenyl cation [457] (or [458]) but rather of a precursor which more resembles the [4.3.2]-system. 

Chang et al. reported a mild tandem intramolecular hydroamination of yne amines to form an enrfo-adduct intermediate, which reacts with electron-deficient azides to produce cyclic amidines <06JA12366>. Selected examples of an interesting synthetic route to tropene derivatives 165 via a dual hydroamination strategy is shown below. This one-step reaction makes use of a palladium catalyst and takes place by sequential intermolecular hydroamination of cycloheptatriene with aryl, heteroaryl, and primary alkyl amines to generate intermediate 166, followed by transannular intramolecular hydroamination <06JA8134>. 

An asymmetric Simmons-Smith reaction was reported by Kang et al. [18]. The reaction of (3-D-fructopyranoside 13 with a,(3-unsaturated aldehydes gave enrfo-acetals 14 along with exo-isomers 15 in a ratio of about 1.5 1. The enrfo-acetals afforded the best selectivity, typically giving (2/f,3/f)-hydroxymethyl cyclopropanes 17 with up to 85% ee. It should be noted that the corresponding exo-acetals 15 underwent the cyclopropanation reaction with lower stereoselectivity. In these cases, the group cannot effectively block either side of the alkene in contrast to the endo-isomer [18] (Scheme 10.3). 

With palladium(O) in the presence of phosphane ligands, the selectivity of the reaction is much lower. Besides 67% polymeric material, a 33% combined yield of cycloaddition products is obtained with a palladium/triphenylphosphane molar ratio of 1 1 after 2 hours at room temperature with complete conversion. The cycloaddition products consist of the dimer 30 (12%), methyl 3,3,7,7-tetramethoxy-exo-tricyclo[4.1.0.0 ]heptane-5-acetate (32, 71%) as the decomposition product of the primarily formed 5-(2,2-dimethoxyethenyl)-3,3,7,7-tetramethoxy-e.V( -tricyclo[4.1.0.0 ]heptane (31), and 3,3,6,6,9,9,12,12-octamethoxy-exo,enrfo,cxo-pentacyclo [9.1.0.0 . 0 . 0 i°]dodecane (33, 17%). 

Enzymes are outstandingly active and highly selective catalysts [332], however, their use in synthesis is often limited by the lack of appropriate cofactors. Reduced nicotinamide cofactors, NADH and NAD(P)H play an important role in many enzyme-catalyzed reactions of practical interest. For example, cyclohexanone and 2-norbomanone was reduced by horse liver alcohol dehydrogenase to afford cyclohexanol, exo-norbomanol (72 %, 38 % e.e.) and enrfo-norbomanol (28 %, 100 % e.e.) on the expense of NADH [333] (Scheme 3.52). 

The thermal hetero-Diels - Alder reaction of diene 1 a to butyl glyoxylate (2 a) leads to a mixture of four possible diastereomers 3-6 in good yield with a predominance of enrfo-attack (jS-sugar) and a d.r. 69 31 in favor of the L-sugar. Dienes lb andc, in the same reaction, produce almost equal amounts of endo- and exo-products with a low selectivity in the formation of new stereogenic centers at C-5 (carbohydrate nomenclature)23-25. 

The lithium dienolate 23, generated by treatment of ethyl (Z)-2-bromo-2-butenoate (22) with lithium diisopropylamide, undergoes smooth addition to enones and provides vinylcyclopropane derivatives in good yield15. The simple diastereoselectivity of this formal [2 I 1] cycloaddition is usually mildly moderate, as demonstrated by the addition of 23 to cyclopentenone which affords bicyclo[3.1.0]hexan-2-one 24 as a 57 43 mixture of endolexo-isomers. On the other hand, the diastereofacial selectivity of the carbene equivalent 23 is very high. Thus, the cy-clopentene derivative 25 is attacked only anti with respect to the dioxolane moiety giving the adduct 26 as enrfo/ew-isomers. 

The enhancement in reactivity and selectivity induced by an internal lxwis base is such that n-PrMgCI and n-BuMgCl, normally significantly less reactive than LlMgCI. can he used in the metal-catalyzed process with the more reactive bicyclic homoallylic alcohols and ethers shown in Table 4.5. Whereas reactions of exo-5-norbornen-2-ol with n-PrMgCl and n-BuMgCI yield <15% of the two exo alkyl isomers non-selectively, enrfo-5-norbornen-2-ol (4 equiv of /r-alkylMgCI, 10 mol ck CpiZrCh. 25 C)... 

When copper catalysed, indene for instance reacts with diazoacetates to give either exo- or enrfo-cyclopropanes (see Figure 7.26). ° The distinct difference in the selectivities achieved by using different concave 1,10-phenanthrolines lies in the different geometry of the ligands. 

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