Six-membered transition structures

X-Substituted Allyl Anions. Allyl anions with alkyl substituents almost always react with carbonyl electrophiles at the more substituted a position, as in the reaction of the prenyl Grignard reagent with aldehydes to give the product 4.39, presumably because the metal attaches itself preferentially to the less-substituted end of the allyl system and then delivers the electrophile in a six-membered transition structure 4.38. In contrast, alkylation of a similar anion with an alkyl halide gives mainly the product 4.40 of y attack, which is normal for an X-substituted allyl anion when a cyclic transition structure is not involved. 

The reaction of ( )- and (Z)-71 with aldehydes has been demonstrated to proceed smoothly with high regio- and diastereoselectivity [50]. Reaction of the ( )-71 provides almost exclusively the syn homoallylic alcohols, while (Z)-71 provides the corresponding anti alcohols. The stereochemical course of the reaction has been attributed to the intermediacy of a chairlike, six-membered transition structure assembly which incorporates all three elements and places the C(3) substituent in pseudoequa-torial or pseudoaxial orientations according to olefin geometry (Scheme 10-29). 

Enantiomerically pure allyl(triethoxy)silanes (82) react readily with aldehydes to provide homoallylic alcohols (Scheme 10-35) [62]. The y-carbon of the allylsiliconate attacks the aldehyde on the same side of the allyl group syn Sg). The observation of high syn-relative diastereoselectivity and high syn S (internal diastereoselec-tivity) is readily explained by a cyclic six-membered transition structure. 

The transmetallation or the metal-metal exchange reaction of an allylic tin species with an electrophile was first observed in 1970 [77]. The possibility that transmetallation may play a role in the Lewis acid-promoted reaction of allylstannanes with aldehydes was initially discussed by Tagliavini [78], Keck [79], Yamamoto [71b, 80], and Maruyama [81]. It is believed that upon transmetallation with either SnCU or TiCl4, the addition of an allylstannane and aldehyde will occur via a cyclic, six-membered transition structure. The reaction occurs by coordination of the aldehyde carbonyl with the Lewis acidic trichlorotin or trichlorotitanium reagent, thus affording the anti homoallylic alcohol (Scheme 10-42). 

The thermally promoted reaction of an enantiomerically pure a-alkoxyallylstan-nane with achiral aldehydes was first reported by Thomas in 1984 [100]. The a-alkoxyallylstannane 145 (prepared from menthol and a racemic stannol) is heated with the aldehyde at 130°C to produce the homoallylic alcohol 146 as a single diastereomer in good yield (Scheme 10-62). Chairlike, six-membered transition structures can account for the observed diastereoseleetivity in these reactions. The a-alkoxy group prefers to adopt an axial position in the transition structure, ensuring that the diastereomers 145 and 147 react selectively with the aldehyde from only one face of the carbonyl group. 

The addition of a 160 to achiral aldehydes in the presence of SnCU produces only the anti homopropargylic alcohols (Scheme 10-67) [106]. The reaction is believed to proceed via transmetallation of the tributyistannyl moiety to the tri-chlorostannyl group. The formation of the anti product then occurs by a syn Skj2 pathway through a cyclic six-membered transition structure (product ee was identical to the ee of 160). 

The asymmetric allylboration of achiral aldehydes with a substituted chiral al-lylborolane 193 and ( )- or (Z)-194 has been reported [128]. The enantioselectiv-ity observed with (5)-193 at -100 C and aldehydes is uniformly high with all of the achiral aldehydes examined (Scheme 10-75). The enantioselection observed with the borolane 193 is proposed to be primarily steric in origin and not from any stereoelectronic component. The reaction likely proceeds via a closed, six-membered transition structure in which the aldehyde is coordinated such that the trimethylsilyl group is oriented anti to the developing B-0 bond. 

For the allyl ether/Me3Si+ system the usual ether reaction , i.e. loss of an olefin via a four-centre elimination, is a minor process. The two major decomposition pathways occur through six-membered transition structures (reactions 115, 116) and, obviously, involve the allylic double bond. Quite remarkable is the methyl transfer 293- 295. 

Fig. 3 The optimized six-membered transition structures with selected bond lengths (in angstroms). Their relative Gibbs free tmergies are in kcal/mol. Calculated at the B3LYP/...

To confirm these suggested acceleration reactions, Ariffin et al. [76] estimated the activation energy value a of the 0-elimination via a pseudo-six-membered transition structure by well-known... 

Dorigo, A. E. and Houk, K. N., Transition structures for intramolecular hydrogen-atom transfers the energetic advantage of seven-membered over six-membered transition structures, /. Am. Chem. 

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. 

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. 

The availability of a six-membered transition state, although necessary, is not always sufficient for an intramolecular hydrogen abstraction to take place. The distance X-Y (structure 95a) also must fall between certain critical limits, usually attainable in nonrigid aliphatic systems but often unsatisfied in rigid situations, i.e., steroids. 

Enantioselective condensation of aldehydes and enol silyl ethers is promoted by addition of chiral Lewis acids. Through coordination of aldehyde oxygen to the Lewis acids containing an Al, Eu, or Rh atom (286), the prochiral substrates are endowed with high electrophilicity and chiral environments. Although the optical yields in the early works remained poor to moderate, the use of a chiral (acyloxy)borane complex as catalyst allowed the erythro-selective condensation with high enan-tioselectivity (Scheme 119) (287). This aldol-type reaction may proceed via an extended acyclic transition state rather than a six-membered pericyclic structure (288). Not only ketone enolates but ester enolates... 

Various bimolecular assemblies that have been proposed for the transition state are shown in Scheme 13 (14, 19a, 20g). Bicyclic transition state A involves transfer of bridging alkyl group (R) to the terminally located aldehyde, while transition structure B involves reaction between terminal R and bridging aldehyde. The reaction may proceed via mono-cyclic, boat-like six-membered transition state C. Transition structures of types B and C were originally proposed for the reactions of orga-noaluminum compounds and carbonyl substrates (26, 27). Ab initio calculations suggest that methyllithium dimer reacts with formaldehyde through a bicyclic transition state related to A (28). The dinuclear Zn... 

A kinetic study of structural effects on the A-nitrosation of amino acids by nitrite in aqueous solution has established that the dominant term in the rate equation corresponds to nitrosation by dinitrogen trioxide.189 Nitrosation by intramolecular migration of the nitroso group from an initially nitrosated carboxylate group can compete when the transition state has a five- or six-membered ring structure. Nitrosation of A-methyl-4-tolylsulfonylguanidine involves rapid nitrosation of the N-... 

Kinetics of the gas-phase elimination of 2-hydroxynitroalkanes have been investigated at the MP2/6-31G level of theory.31 The thermal elimination of 2-hydroxynitroalkanes occurs in a retro-aldol type of mechanism with a six-membered transition state structure characterized by the transference of the hydroxyl hydrogen to the nitro group to give acetaldehyde and the corresponding nitroalkane for the secondary substrates and acetone and nitromethane for the tertiary substrate. 

To explain the stereochemical outcome of the reaction of allylic boron reagents with carbonyl compounds, Houk and Li carried out calculations on the transition structures of the model reaction of formaldehyde and allylboronic acid6 (Scheme 3.V). The bimolecular complex formed initially between allylboronic acid and formaldehyde would rearrange via a six-membered transition state to form an intermediate. Calculations show that chair transition state A is 8.2kcal/ mol more stable than twist-boat transition structure B, clearly confirming that the six-membered chairlike transition-state model is a legitimate scheme to predict the stereochemical outcome of the boron allylation reaction. 

A comparison of the degrees of polymerization and of the molecular mass distribution curves of the products may help to reveal the nature of the reactions which occur. Another kind of degradative transfer was described by Scott and Senogles [12]. It involves intramolecular transfer with the formation of a non-propagating centre and occurs during the generation of chains with a tendency to form five- and six-membered cyclic structures as a transition stage... 

Hydrogen abstraction via a six-membered transition state is no longer feasible when the double bond is moved one carbon out of conjugation with the dione as in 4,4,5-trimethyl-5-hexene-2,3-dione (153). The product, obtained in over 90 % yield 113), was the bicyclic ketooxetane 154. This appears to be an intramolecular example of the well-known photoaddition of diones to alkenes (cf. Section IXA). The structure of 154 appears to be well-established and to exclude any possibility of a fast isomerization, involving 1,3-acyl migration, to 155. 

Amazingly, all central C=C bonds were 98% trans, a remarkable stereoselectivity for any reaction. This fact rules out the intervention of an Syl route—unless some inexplicable stereocontrol is in operation. Since the transition state must embody rotational restrictions, the mechanism would not be invalidated. In this bimolecular approach the incoming and departing groups would be somehow associated as to discourage rotation of the carbon skeleton. Structure III, for example, would contain a comfortable six-membered transition state that should fulfill this requirement thoroughly, although it is unprecedented. 

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