Endo-substituents

Endo (Section 14.5) A term indicating the stereochemistry of a substituent in a bridged bicycloalkane. An endo substituent is syn to the larger of the two bridges. 

The second factor used to support the non-classical position is the high exojendo rate ratio usually found in solvolysis. The high ratios have been taken as evidence for delocalization of the a electrons of the bond between C-1 and C-6 into the rear of a developing p-orbital at C-2 as an ex o-substituent ionizes. Similar delocalization during the ionization of an endo-substituent is not anticipated because of poor orbital alignment. 

The basic differences in electron delocalization between the homoaromatic homotropenylium and homocyclopropenium ions and the bicyclo[3.1. Ojhexenyl cations result in fundamentally different reactions of these cations. As was noted earlier, the homotropenylium and homocyclopropenium ions undergo a characteristic ring-inversion process which interconverts the exo and endo substituents on the methylene bridge. With 61 and its derivatives no such reaction occurs. Rather, two different types of thermal isomerization occur. The first of these is the irreversible rearrangement to the cyclo-hexadienyl ions mentioned above. The second thermal isomerization involves a circum-ambulation of the methylene group around the periphery of the five-membered ring,37-143.,45.152. 

With a titanacyclobutane complex as initiator the rate of polymerization is independent of [M] and therefore governed by the rate of opening of the titanacyclobutane chain carrier432. The comparative stability of the metallacyclobutane bearing an endo substituent is a feature which is also found in the ROMP of other substituted norbomenes see Section Vm.C.12. In contrast, the rate of ROMP of 235 induced by ReCl5/Me4Sn (1/1.5) is first-order in both catalyst and monomer and here the addition of monomer to the metal carbene complex must be rate-determining562. 

The basic skeleton of these compounds is 2,9-dioxa-bicyclo[3.3.1]nonane (57), which has limited steric flexibility. 1,7-Anhydroheptoses adopt predominantly the twin-chair conformation 57a, provided that no endo substituents are present at positions C-3 and C-7 to cause steric interactions. Otherwise, flattened boat-like and skew conformations may also play an important role. 

An unusual cyclopropanation of 9-bromocamphor derivatives (5) to a 7-spirocyclo-propyl camphor derivative (6) has been realized by the action of potassium r-butoxide (or sodium hydride) in warm DMSO (Scheme 8).29 The exo-hydroxy group and a nonhydrogen endo-substituent at C(2) were proven to be essential structural elements, and the solvent DMSO the sole effective reaction medium. 

Groups that are cis to this bridge are termed exo substituents, and groups that are trans to this bridge are termed endo substituents. 

The diastereoselective allylindium addition to norbornyl cr-diketones leads to acyloins. The diastereoselection in the case of monoallylation products greatly depends on the nature of 5-endo substituents. Non-chelating groups direct the addition from the sterically less congested exo-face, diagonal to the substituent, whereas chelating substituents, such as an alkoxy or acetoxy unit, induce a complete reversal in the selectivity (Equation (16)).169... 

More remote substituents may also participate in epoxide opening/rearrangement. Christol and coworkers examined several S,(6)-substituted-2,3-norbomene ejco-oxides under acidic conditions, and found that certain 5-endo substituents played a part in oxirane opening. For example, oxa rings were formed in reactions of substrates bearing 5-entfo-methoxycarbonyl or -hydroxymethyl groups. A novel 1,4-migration of chloride was also detected (equation 28). ... 

Note how the cis product is obtained in the metalla-ene reaction. This stereochemical result reflects the preference of this particular substrate for an endo transition state, just as in cycloadditions. In cycloadditions, though, the endo substituent of the dienophile is usually an electron-withdrawing substituent, whereas in this ene reaction the endo substituent of the enophile is simply the alkyl chain joining it to the ene. 

Acetonation of D-talose in the presence of anhydrous copper(II) sulfate and sulfuric acid gave, as the major product, the 2,3 5,6-diacetal (28%) with a smaller proportion of the 1,2 5,6-diacetal (10%).16 These results are in accordance with the predictions of Mills10 that the 2,3 5,6-diacetals of mannose, gulose, allose, and talose would be thermodynamically favored, as they have the minimum number of endo substituents. 

The condensation of acetone with D-ribose, with sulfuric acid as the catalyst, has also been examined in detail.17 The major component is 2,3-O-isopropylidene-D-ribofuranose (59%), together with three minor components l,5-anhydro-2,3-0-isopropylidene-D-ribofuranose (9%), 1,2 3,4-di-O-isopropylidene-a-D-ribopyranose (3%), and 1,2-0-isopropylidene-a-D-ribofuranose (6%). The authors observed that the only marked difference when other catalysts (such as copper sulfate or zinc chloride) were used was the absence of the anhydro compounds. Assuming that the 1-hydroxyl group is equatorial, the preponderance of the 2,3-acetal is consistent with the thermodynamic stability of the isomer having the least number of endo substituents and with the unfavorable interactions between the acetal rings in the 1,2 3,4-diacetal, which possesses a cis-syn-cis arrangement of rings.10... 

Due to a strong preference for exo attack, indirect methods are required to install endo substituents. For example, addition reactions which proceed through bridged cationic intermediates cause other nucleophilic species to add from the endo face. Hence, endo halide substitution follows bromonium and selenonium ion formation. A striking example of this phenomenon is the inter-... 

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