Six-membered transition state

Protonolysis. Simple trialkylboranes are resistant to protonolysis by alcohols, water, aqueous bases, and mineral acids. In contrast, carboxyUc acids react readily with trialkylboranes, removing the first alkyl group at room temperature and the third one at elevated temperatures. Acetic and propionic acids are most often used. The reaction proceeds with retention of configuration of the alkyl group via a cycHc, six-membered transition state (206). 

The selectivity observed in most intramolecular functionalizations depends on the preference for a six-membered transition state in the hydrogen-atom abstraction step. Appropriate molecules can be constmcted in which steric or conformational effects dictate a preference for selective abstraction of a hydrogen that is more remote from the reactive radical. 

The formation of the less favored trisubstituted isomer (37) occurs by the usual intramolecular axial proton transfer from the 6 position, whereas that of the tetrasubstituted isomer (38) involves the intramolecular proton transfer of the stereoelectronically less favored equatorial proton either via a four-membered transition state (39) or a six-membered transition state (40). 

The first column corresponds to six-membered transition states where two types can be differentiated situation A, where the proton transfer leads to a neutral tautomer, and situation B (often Tinuvin P or TIN 75), where the proton transfer leads to a zwitterionic tautomer (Scheme 25). 

Upon the irradiation the nitrous acid ester 1 decomposes to give nitrous oxide (NO) and an alkoxy radical species 3. The latter further reacts by an intramolecular hydrogen abstraction via a cyclic, six-membered transition state 4 to give an intermediate carbon radical species 5, which then reacts with the nitrous oxide to yield the 3-nitroso alcohol 2 ... 

There is quite some evidence for a mechanism as formulated above,especially for the six-membered transition state—the Barton reaction is observed only with starting materials of appropriate structure and geometry, while the photolysis of nitrite esters in general seldom leads to useful products formed by fragmentation, disproportionation or unselective intermolecular hydrogen abstraction. 

As a consequence of the pericyclic reaction path, the addition of a-stereogenic allylmctals to carbonyl compounds is accompanied by an effective 1,3-chirality transfer in the allylic moiety combined with 1,4-chira induction at the prostereogenic carbonyl group3032. The scheme also demonstrates the importance of the orientation of the substituent X in the six-membered transition state. By changing from a pseudo-axial to a pseudo-equatorial position, the cation-induced sy/i-attack addresses opposite faces of both prostereogenic moieties, leading to a Z-and an -isomer, these being enantiomeric in respect to the chiral moiety. 

In this case, /6 -attack at the carbonyl group is induced by the stereogenic center at the metal. This fact is best explained by an approach of the aldehyde trans to the nitroso group, forming a chair-like six-membered transition state in the lower half-sphere which is not shielded by the cyclopentadiene residue. 

Williams56 argues that these aldol-type condensations do not proceed via cyclic, chairlike six-membered transition states, in contrast to previous arguments to the contrary58., ... 

The Diels-Alder reaction is a pericyclic cycloaddition when bond-forming and bond-breaking processes are concerted in the six-membered transition state... 

Here too there is an enol that tautomerizes to the product. The mechanism is illustrated for the case of P-keto acids, ° but it is likely that malonic acids, a-cyano acids, a-nitro acids, and P,y-unsaturated acids behave similarly, since similar six-membered transition states can be written for them. Some a,P-unsaturated acids are also decarboxylated by this mechanism by isomerizing to the p,y-isomers before... 

In others, there is a five- or a six-membered transition state. In these cases, the addition to the double or triple bond must be syn. The most important reaction of this type is the Diels-Alder reaction (15-58). 

DeDnA in the lUPAC system. The elimination must be syn and, for the four- and five-membered transition states, the four or five atoms making up the ring must be coplanar. Coplanarity is not required for the six-membered transition state, since there is room for the outside atoms when the leaving atoms are staggered. 

The mechanism is Ei (see p. 1322). Lactones can be pyrolyzed to give unsaturated acids, provided that the six-membered transition state required for Ei reactions is available (it is not available for five- and six-membered lactones, but it is for larger rings ). Amides give a similar reaction but require higher temperatures. 

As we have indicated with our arrows, the mechanism of the uncatalyzed Cope rearrangement is a simple six-centered pericyclic process. Since the mechanism is so simple, it has been possible to study some rather subtle points, among them the question of whether the six-membered transition state is in the boat or the chair form. ° For the case of 3,4-dimethyl-l,5-hexadiene it was demonstrated conclusively that the transition state is in the chair form. This was shown by the stereospecific nature of the reaction The meso isomer gave the cis-trans product, while the ( ) compound gave the trans-trans diene. If the transition state is in the chair form (e.g., taking the meso isomer), one methyl must be axial and the other equatorial and the product must be the cis-trans alkene ... 

The rearrangement follows first-order (in the phosphazene) kinetics and the rate increases as the electron density supplied by the substituents A and B increases. It was suggested that the reaction proceeds via a six-membered transition state such as (30). 

The importance of the six-membered transition state for hydrogen transfer to form the ketene is clearly demonstrated by the 17-fold increase in the ketene addition product (X = NHR) in proceeding from a five-membered transition state to a six-membered transition state above/36,37 ... 

Intramolecular hydrogen abstraction. As stated above, photolysis of n-octylnitrite results in a predominance of the product corresponding to intramolecular hydrogen abstraction. Photolysis of 3-heptyl, 2-hexyl, and 2-pentylnitrites yields intramolecular hydrogen abstraction products in 28%, 31%, and 6% yields, respectively/5 In each case the product corresponded to hydrogen abstraction via a six-membered transition state ... 

Photolysis of 2-propylnitrite, in which intramolecular hydrogen abstraction cannot occur via a six-membered transition state, results in a 30% yield of 2-propanone. As we shall see, this intramolecular hydrogen abstraction has been extensively applied to steroid syntheses by D. H. R. Barton and hence is commonly referred to as the Barton reaction. 

Observation of the Norrish Type II reaction presents some difficulty in that generation of the biradical intermediate 12 requires a six-membered transition state and this is in conflict with the linear guest arrangement normally expected in the channel. However, as noted earlier, accommodation of planar six-membered rings in urea inclusion complexes has been observed 38. It appears that in this case the necessary six-membered transition state can be produced in the channel without destruction of the crystal structure. 

So far as thermal reactions are concerned, those that can proceed via six-membered transition states go most readily, and are by far the commonest. That a six-membered cyclic T.S. in the chair conformation is commonly preferred is shown by the fact that the meso form of (49) yields only (99.7%) the cis,trans form (50a), out of the three possible geometrical isomerides (cis,cis, cis,trans and trans,trans) of (50) ... 

This reaction also is concerted and proceeds via a six-membered transition state, but here the species (59), corresponding to the ene-one intermediate (53a) in the aromatic Claisen rearrangement, is in fact the end-product. This is so because there is in (59) no energetic driving force, comparable to re-aromatisation in (53a— 52a), to promote its enolisation. 

The selective generation of syn-isomers can plausibly be explained by the formation of (Z)-enolates 2-73 via 2-72 in the addition step and by a six-membered transition state 2-75 in the subsequent aldol reaction. 

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