Exo reactions

CSTR WITH FIRST-ORDER EXO. REACTION AND JACKET... 

The broken lines in the diagrams show the trace of the plane of the n orbitals. A reaction will occur readily if X lies on this plane and makes an obtuse angle with the C=Y bond. Molecular models show that the carbon backbone is long and flexible enough to satisfy both of these criteria for the exo reactions. The 6-endo reaction poses problems. If X lies in the n plane, the carbon skeleton has to adopt a boat conformation, leading to a perpendicular attack. However, if X moves slightly out of the n plane, an acceptable compromise can be achieved the attack trajectory becomes non-perpendicular, with a fair nucleophile-n overlap. However, neither condition can be satisfied for a 5-endo reaction. Note that a direct application of Baldwin s empirical rules would have masked these subtleties. 

Krief has applied selenium chemistry to some anionic cascade cyclisations.128 For example, 293 can be cyclised in two successive 5-exo reactions to give a mixture of the stereoisomers of 297. If 294 is warmed to 0 °C, an alternative sort of tandem process occurs after cyclisation onto the alkene, the organolithium 295 undergoes an intramolecular displacement, stereoselectively generating the 5,3-fused system of 296. Similar intramolecular cyclopropanations (of a-bromo organolithiums) have been described by Hoffmann151 but are probably mediated by carbenes rather than a sequential cyclisation-substitution sequence. 

A endo-5-exo reaction describes a bicyclization with an initial 6-endo and a terminating 5-e.vo ring closure. The prefix trans or cis describes the ring junction and the prefix anti or syn describes the relative stereochemistry of two adjacent carbon centers. 

Type I The 5- and (less) 6-e.w-cyclization product is usually a 2-vinylcyclopentanol or 2-vinylcyclohexanol. The carbonyl ene reaction mechanism is also found for 5-exo and 6-exo reactions. It is worth noting that ene reactions forming cyclopentanols are reversible due to ring strain10. 

Type-Ill cyclizations are initiated by conversion of an acetal, ketal or enol ether into an oxonium ion. Such an activated carbonyl group attacks an olefin intramolecularly in an exo reaction. Mono- and trialkylated double bonds form new C-C bonds regioselectively at the least hindered terminus according to Markovnikov s rule, and in this case endo cyclization products can be produced25. It is worth noting that acetals are also used as initiators in cation olefin cyclizations (see Section 1.5.5.3.)26. Use of activated acetals in Lewis acid catalyzed C-glycoside synthesis is also known 12c 12e. 

A 5-exo reaction can be observed when ,/Tepoxycyclohexenone is treated with tin(lV) chloride. After a regioselective oxirane ring opening, cyclization follows via axial attack of the alkyne group. The terminal vinyl cation is trapped by chloride and the bicyclo[4 3.0]nonan-2-one system 1 is formed stereoselectively in 94% yield5. 

Ionization of allylic systems, generating stabilized ions, is one of the most successful methods of inducing cyclization. On treating chiral linalool with protic acids, a 6-exo reaction takes place via a chairlike transition state (concerted mechanism) but the configuration is inverted on building chiral limonene (10)14. 

The first example of an epoxide-induced pentacyclization has been describedlos. The process is separated into a tri- and a consecutive bicyclization. Termination of the initial tricyclization leads to a fluorine-stabilized cation, which simultaneously induces the final bicyclization. The whole process is terminated by a 6-exo reaction of a propargyl silane group. Additionally, some mono- and bicyclic byproducts are isolated105. Further investigations with the well-known... 

Diels-Alder reaction shows a more negative activation volume than the corresponding exo reaction (around —2.5 cm mol ) [41]. Therefore, high pressures have an impact on regio- and stereoselectivity, e.g. by increasing the endo exo ratio [42, 43]. 

The reactivity difference along endo and exo reaction paths has been shown by Berson et to depend clearly, although slightly, on the solvent polarity in the case of cyclopentadiene addition to some acrylic esters on increasing the polarity of the solvent, as defined by the Z parameter " , the logarithm of the endolexo ratio in the adduct increases in a roughly linear manner (Fig. 1). 

Danishefsky et al. have achieved a synthesis of a methyl peracetyl-oc-hikosaminide (216), an undecose degradation product of the anthelmintic hikizimycin, in which use is twice made of the siloxy-diene aldehyde Diels-Alder reaction. Thus, the reaction between the diene (211) and furfural with [EuCfod) ] catalysis leads to the pyrone (212) which, after elaboration to (213), is again condensed with (211), but this time with magnesium bromide catalysis, which causes addition of the remaining four carbon atoms of the undecose in a chelation-controlled and, notably, a topically exo reaction. Elaboration of (215) to the required protected hikosamine (216) then follows in a straightforward manner. 

A methacrylic acid (MAA)-divinylbenzene (DVB) copolymer was noncovalently imprinted with TSAs for the endo- and exo-reaction pathways (5 mol%). The TSAs were prepared by an analogous Diels-Alder reaction between cyclohexa-l,3-dienyl-carbamic acid benzyl ester and N,N-dimethylacrylamide (Scheme 9b). It should be remembered... 

In the competition between the 5-C-exo process with an ester and the 6-C-exo process with a ketone shown in the last equation in Scheme 16, the latter predominates, suggesting that monoesters might not be sufficiently acidicJ Clarification of these subtle points seems to require furthCT investigation. In this connection, the 6-C-exo reaction shown in Scheme 17 is instructive as this represents an extension of potentially high synthetic utility. ... 

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