Endo attack

The preference for endo attack in 7,7-dimethylnorbomene is certainly steric in origin, with the 7-methyl substituent shielding the exo direction of approach. The origin of the preferred exo-attack in norbomene is more subject to discussion. A purely steric explanation views the endo hydrogens at C—5 and C—6 as sterically shieldihg the endo approach. There probably is also a major torsional effect Comparison of the exo and endo modes of reproach shows that greater torsional strain develops in the endo mode of... 

In contrast to the extraordinarily high preference for endo attack observed with camphor (1), nucleophilic additions of organolithium and Grignard reagents to norcamphor (3) proceed with exclusive attack of the nucleophile from the exo face of the carbonyl group. 

Addition of trimethylaluminum to norcamphor (3), regardless of the stoichiometry of the reactants, leads to a mixture of the diastereomeric alcohols in a ratio of 95 5 also in favor of the erafo-alcohol6. Examination of the norcamphor model indicates that endo attack is sterical-ly more hindered than exo attack. However, steric interaction may not fully account for the exceptionally high exo selectivity. On the other hand, no severe torsional strain is involved if the nucleophile approaches the carbonyl group from the exo side, however, a nucleophile approaching from the endo side encounters torsional strain between the incipient bond and the C-l to C-6 carbon-carbon bond. Thus, in the case of norcamphor, steric and stereoelectronic factors reinforce each other, resulting in a strong directional influence for exo attack. 

The formation of alkyl shifted products H and 14 can be explained in terms of the formation of endo-intermediate 21 formed by endo attack of bromine to 2 (Scheme 4). The determined endo-configuration of the bromine atom at the bridge carbon is also in agreement with endo-attack. Endo-Intermediate 21 is probably also responsible for the formation of cyclopropane products 12 and 15. The existence of cyclopropane ring in 12 and 15 has been determined by and 13c NMR chemical shifts and especially by analysis of cyclopropane J cH coupling constants (168 and 181 Hz). On the basis of the symmetry in the molecule 12 we have distinguished easily between isomers 12 and 15. Aryl and alkyl shift products IQ, H, and 14 contain benzylic and allylic bromine atoms which can be hydrolized easily on column material. 

Norbomenone 26 undergoes reduction by sodium borohydride under kinetic conditions to produce 5% exo- (i.e., endo attack) and 95% endo- (i.e., exo attack) 2-norbomeol. This leads to the partial rate constants of 11.4 for exo and 0.6 for endo attack (relative rate with respect to the rate of LiAlH reduction of cyclopen-tanone (1.00)) [80]. In the saturated 2-norbomanone 25, the values are 4.55 for exo and 0.74 for endo attack. Thus, the introduction of the double bond enhances the... 

Diels-Alder reaction is one of the most fundamental reactions for organic synthesis. Its synthetic utility is unquestioned. The stereochemistry of the reactions has attracted much attention. The retention of stereochemistry in the diene and the dienophile, the predominant formation of endo-attack products in the reactions of cyclic dienes, and highly controlled regioselectivity in the reactions of substimted dienes and... 

Secondary orbital interaction had been proposed to explain predominant formation of endo attack prodncts in Diels Alder reaction of cyclopentadiene and dienophiles by Hoffmann and Woodward [22]. According to this rnle, the major stereoisomer in Diels-Alder reactions is that it is formed through a maximum accumulation of double bonds. In the Diels-Alder reactions, secondary orbital interaction consists of a stabilizing two-electron interaction between the atoms not involved in the formation or cleavage of o bonds (Scheme 19). 

As mentioned above, ferrocene is amenable to electrophilic substitution reactions and acts like a typical activated electron-rich aromatic system such as anisole, with the limitation that the electrophile must not be a strong oxidizing agent, which would lead to the formation of ferrocenium cations instead. Formation of the CT-complex intermediate 2 usually occurs by exo-attack of the electrophile (from the direction remote to the Fe center. Fig. 3) [14], but in certain cases can also proceed by precoordination of the electrophile to the Fe center (endo attack) [15]. 

Although the mercuration of ferrocene has been reported for many years, only recently has the mechanism of this reaction been elucidated. Recent studies indicate that the soft mercuric cation undergoes complexation to the Lewis-basic iron center prior to mercuration. This event is followed by the rate-limiting endo-attack of the cyclopentadienyl ring and subsequent product formation (Scheme 7).103... 

Activation of one the double bonds of the allene by coordination to an electrophilic metal center such as Hg(II), Ag(I), Pd(II), Rh(I), Cu(I) or Au(III). Then an intramolecular nucleophile can attack and the product is formed by protodemetallation of the intermediate (Scheme 15.1). Depending on electronic and steric factors, either the proximal or the distal Jt-bond of the allene 1 is activated in that way (2 and/or 3). For each of these two possibilities now an exo or endo attack of the nucleophile is conceivable, leading to intermediates 4—7. An equilibrium between both 5 and 6 and 9 is possible. Finally, from 4 the vinyl-substituted 8 is formed. From 5, 6 or 9 the exocyclic alkene 10 and/or the endocyclic alkene 11 can be observed. Compound 7 would deliver the endocyclic alkene 12. 

Spino and colleagues134 studied the Diels-Alder reactions of vinylallenes aiming to synthesize six-membered rings with a tetrasubstituted exocyclic double bond, which were to be employed as precursors of quassinoids. Some representative results of their investigations have been summarized in Table 5 (equation 56). Due to the presence of two different substituents at the allene terminus of 200, facial differentiation occurred, which resulted in non-equivalent amounts of geometrical isomers 201 and 202. The major isomers obtained in each case were formed by endo attack of maleic anhydride 144 at the less hindered face of the diene. 

In chlorinated solvents the reaction of 49 also gives products of exo and endo attack (exo endo = [151 +155]/[152 + 156] = 39 61), but in this case compounds of simple 1,2-addition are found to predominate. Once again the solvent-dependent product... 

These results have been interpreted in terms of trans addition of mercuric ion and nucleophile where the attack of the mercuric ion takes place from the more hindered side of the diene molecule. A transition state 197, involving an endo attack of mercuric ion with some stabilization by coordination to the 8,9-ethylenic bond to the mercury atom, has been proposed to support the suggested mechanism. Analogously, and in sharp contrast to the results obtained167 in the mercuration of norbomadiene which reacts with mercury salts via the usual scheme of exo-syn addition, the principal pathway in the mercuration of bicyclo[2.2.2]octa-2,5-diene is the formation of endo-syn products (equation 165). 

In the hydrolysis of the tosylate (21a) the predominance of exo isomers (21b) relative to endo isomers indicated the importance of steric hindrance of the C( 1) Me group to endo attack by the nucleophile. An analogous result was found for the products of bromination (21d) of the corresponding iodides (21c). 

Chiral 4,4-disubstituted cyclohexenones.1 The chiral bicyclic lactam 2, obtained by reaction of 4-acetylbutanoic acid with 1, on dialkylation gives mainly the diastereomer from endo-attack, with the highest diastereoselectivity obtained by using the larger electrophile in the second alkylation. Hydride reduction followed by hydrolysis furnished 4,4-dialkylated cyclohexenones (4) in >95% ee. 

Endo attack is preferred in some 1,3-dipolar cycloadditions. 

CASSCF calculations.7 Treatment of substituted 5-triethylsilyloxyhexa-l,2,5-triene derivatives with catalytic amounts of W(CO)6 was found to give the products of formal Cope rearrangement 2-triethylsilyloxyhex-l-en-5-ynes. The mechanism is believed to involve 6-endo attack by the silyl enol ether on the tungsten-activated allene, followed by ring opening with simultaneous loss of W(CO)s.8... 

Two main explanations were considered. First, the endo-attack may be hindered by non-bonding interactions of the hydrogen atoms at the 5- and 6-positions with reacting D20 this hypothesis was ruled out since the exo/endo ratio is still high for dehydronorcamphor [33] (exo/endo = 120) and for benzonorbornenone [34] (exo/endo w 700), i.e. in the absence of hydrogen... 

Another example features a Heck-type 5-exo-trig cyclization of the aryl iodide 139 occurring at room temperature in dichloromethane (Scheme 22) [82], Azomethine ylides originating from imines 133 were used to trap the Heck product 140 in a subsequent 1,3-dipolar cycloaddition. The diastereomeric products 141 and 142 both derive from an endo attack of... 

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