Acyclic transition state

Ethyl (Z)-2-bromomethyl-2-heptenoate and aldehydes condense on reaction with chromium(II) chloride to furnish cw-3,4-disubstituted dihydro-3-methylene-2(3 //)-( uranones exclusively16, indicating that a (Z)-allylchromium complex might serve as reactive intermediate in the. mv-selec-tive addition step due to the bulky 2-substitucnt. Alternatively, an acyclic transition state for the reaction of the ( )-diastereomer, mediated by the Lewis acid dichloroaluminum hydride, has been discussed16. 

Extended acyclic transition states, such as G are also possible since, after the transmetalation, two additional equivalents of diethylaluminum remain that may serve as a Lewis acid26,44. 

The configurational course depends on the enolatc configuration and the metal ion which determines whether a cyclic (e.g., Zimmerman-Traxler type) or an acyclic transition state is traversed. At present the following transition state models have been proposed. 

The relative configuration of the diastcrcomers obtained on reaction of A-benzoyl a-methoxy-glycine methyl ester and various activated cyclohexenes is dependent on the cyclohexene substituent88. Whereas the boron trifiuoride catalyzed reaction with l-(4-morpholinyl)cyclohexene gives predominantly the awt/ -isomer, the. vrn-isomcr is predominantly formed in the titan-ium(IV) chloride catalyzed reaction with trimethylsilyloxycyclohexene. These results arc explained by a cyclic and an acyclic transition state, respectively. As expected, acetoxycyclohex-ene is less reactive. 

The chemical reactions through cyclic transition states are controlled by the symmetry of the frontier orbitals [11]. At the symmetrical (Cs) six-membered ring transition state of Diels-Alder reaction between butadiene and ethylene, the HOMO of butadiene and the LUMO of ethylene (Scheme 18) are antisymmetric with respect to the reflection in the mirror plane (Scheme 24). The symmetry allows the frontier orbitals to have the same signs of the overlap integrals between the p-or-bital components at both reaction sites. The simultaneous interactions at the both sites promotes the frontier orbital interaction more than the interaction at one site of an acyclic transition state. This is also the case with interaction between the HOMO of ethylene and the LUMO of butadiene. The Diels-Alder reactions occur through the cyclic transition states in a concerted and stereospecific manner with retention of configuration of the reactants. 

Reactions of chiral silanes with chiral aldehydes exhibit matching and mismatching characteristics (Eqs. 9.56 and 9.57) [48]. The additions proceed through an acyclic transition state, which favors syn adducts. The matched (M)/(R) pairing of Eq. 9.56 proceeds by way of a favorable Felkin-Anh arrangement to afford the syn,syn homopropargylic alcohol product. However, if the silanes possess an a-hydrogen, a vinylic chloride intermediate is formed, as shown in Scheme 9.13. Subsequent treat-... 

Scheme 9.18). The BF3 OEt2-promoted additions also proceed via acyclic transition states but the diastereoselectivity results from Felkin-Anh control. 

The differing steric outcomes of these cyclizations can be understood on the basis of an acyclic transition state in the former case and a coordinated cyclic transition state in the latter (Scheme 9.22). 

It was postulated that the role of the triflate reagent 69 is to activate the acetal, with the possible intervention of either 79 or 80 as the putative electrophUic species, which undergoes reaction with the enolsilanes via the extended acyclic transition state 81 (4). Based on the assumption that transition state R2 R3 interactions from either enolate geometry dictate the stereochemical course of... 

Diastereoselectivity in the aldol and the conjugate additions of 2 -hydroxy-1,T-binaphthyl ester enolates with a variety of carbonyl electrophiles has also been explored the tendency of the ester enolates, generated by BuLi, to react with aldehydes to give threo products preferentially with high diastereoselectivity has been interpreted in terms of an acyclic transition state of chelated lithium enolate involving the aldehyde carbonyl and the 2 -hydroxy group. 

It was found that benzaldehyde reacts with E and Z configured silyl ketene acetals to furnish identical aldol products [93] with high enantioselectivity. Neither diastere-oselectivity nor enantioselectivity were affected by double bond geometry of the silyl ketene acetal. This is an evidence for an acyclic transition state (Scheme 27). 

If there is no other interaction, such a reaction should proceed through an acyclic transition state, and steric factors should determine the amount of syn versus anti addition.41 This seems to be the case with BF3, where stereoselectivity increases with the steric bulk of the silyl enol ether substituent R1 42... 

If HMPA is included in the solvent, the Z-enolate predominates.162 DMPU also favors the Z-enolate. The switch to the Z-enolate with HMPA or DMPU can be attributed to a loose, perhaps acyclic, transition state being favored as the result of strong solvation of the lithium ion by HMPA or DMPU. The steric factors favoring the E transition state are therefore diminished.163 These general principles of solvent control of enolate stereochemistry are applicable to other systems.164... 

Although the allylation reaction is formally analogous to the addition of allylboranes to carbonyl derivatives, it does not appear to occur through a cyclic transition state. This is because, in contrast to the boron in allyl boranes, the silicon in allylic silanes has no Lewis acid character and would not be expected to coordinate at the carbonyl oxygen. The stereochemistry of addition of allylic silanes to carbonyl compounds is consistent with an acyclic transition state. Both the E- and Z-stereoisomers of 2-butenyl(trimethyl)silane give the product in which the newly formed hydroxyl group is syn to the methyl substituent.64 The preferred orientation of approach by the silane minimizes interaction between the aldehyde substituent R and the methyl group. 

The stereoselectivity is higher for the /i-stannanc.114 This stereochemistry is the same as that observed for allylic silanes and can be interpreted in terms of an acyclic transition state. (See page 571). Either an anti or gauche conformation can lead to the preferred syn product. An electronic n interaction between the stannane HOMO and the carbonyl LUMO is thought to favor the gauche conformation.115... 

Apart from cyclic or acyclic transition state geometry further distinctions of diastereoselec-tion have to be made with respect to the way in which the chiral center is attached to the reactive site. The term auxiliary control is used if a chiral subunit, e.g., an alcohol or an amine, is fixed covalently to the unsaturated substrate and then removed by bond cleavage after the addition. In contrast, if the stereogenic center remains part of the molecule after the addition, the term substrate control is applied (these definitions are given in Section A. 1.). 

Chiral allenylmetal compounds provide convenient access to enantioenriched homopropargylic alcohols through SE2 additions to aldehydes.3 The syn adducts can be obtained through addition of allenyl tributylstannanes in the presence of stoichiometric boron trifluoride etherate (BF3OEt2). The use of allenylmetal halides derivatives of Sn, Zn, and In lead to the anti diastereomers. The former additions proceed through an acyclic transition state whereas the latter are thought to involve a cyclic transition state, thus accounting for the difference in diastereoselectivity. 

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... 

Eliminations of H/Het via Acyclic Transition States The Mechanistic Alternatives... 

Let us now turn to /3-eliminations that take place via acyclic transition states. There three elimination mechanisms (Figure 4.16) depending on the order in which the C—H and the C—Het bonds of the substrate are broken. If both bonds are broken at the same time, it is a one-step E2 elimination. When first one and then the other bond is broken, we have two-step eliminations. These can take place via the El or the Elcb mechanism. In the El mechanism, the C— Het bond is broken first and the C—H bond is broken second. Conversely, in the Elcb mechanism the C—H bond is broken first, by deprotonation with a base. In this way the conjugate base (cb) of the substrate is produced. Subsequently, the C—Het bond breaks. 

Fig. 4.16. The three mechanisms of H/Het-elimination via acyclic transition states ba the attacking base baH the protonated base EWG electron-withdrawing group...

In isolated cases diastereoselectivity is reversed 2S>. Either acyclic transition states are transversed, or the usual pericycles are involved, having chair or boat conformations depending upon the enolate geometry, the substituents and the nature of the aldehyde 25>. These possibilities have also been discussed in irregularities reported for other enolates 48 109-m). For example, dicyclopentadienylchlorozirconium-109>, triphenyltin u0> and tris(dialkylamino)-sulfoniumnl> (TAS) enolates also favor... 

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