Transition antiperiplanar

Model calculations generally support Felkin s hypothesis35-38. However, an additional controlling factor is the stabilization of the transition state by the approach of the nucleophile antiperiplanar to a vicinal bond35. In the transition state for axial attack (Figure 8), the incipient bond is approximately antiperiplanar to two axial C — H bonds. Flattening of the ring improves this antiperiplanarity and, therefore, the more flattened the cyclic ketone, the more axial attack is preferred. 

Since equatorial attack is roughly antiperiplanar to two C-C bonds of the cyclic ketone, an extended hypothesis of antiperiplanar attack was proposed39. Since the incipient bond is intrinsically electron deficient, the attack of a nucleophile occurs anti to the best electron-donor bond, with the electron-donor order C—S > C —H > C —C > C—N > C—O. The transition state-stabilizing donor- acceptor interactions are assumed to be more important for the stereochemical outcome of nucleophilic addition reactions than the torsional and steric effects suggested by Felkin. 

An open-chain antiperiplanar transition state was initially proposed for this reaction74, although a synclinal alternative has since been suggested56. 

The stereoselectivity of the boron trifluoride induced reactions was initially discussed in terms of open-chain, antiperiplanar transition states66. However studies of Lewis acid induced intramolecular allylstannane-aldehyde reactions are supportive of a synclinal process56,67. 

The stereoselectivity of these intermolecular reactions between 1-alkoxyallylstannanes and aldehydes induced by boron trifluoride-diethyl ether complex is consistent with an open-chain, antiperiplanar transition state. However, for intramolecular reactions, this transition state is inaccessible, and either (Z)-.yyn-products are formed, possibly from a synclinal process105, or 1,3-isomerization competes113. Remote substituents can influence the stereoselectivity of the intramolecular reaction114. 

The diastereoselectivity of this reaction contrasts dramatically with the generally low selectiv-ities observed for aldol reactions of lithium enolates of iron acyls. It has been suggested thal this enolate exists as a chelated species48 the major diastereomer produced is consistent with the transition state E which embodies the usual antiperiplanar enolate geometry. 

The preferential conversion of the aluminum enolatc 2 c to diastereomer 3 is consistent with the boat-like transition state A where the enolate has adopted the usual antiperiplanar E geome-try42-50. The aldehyde substituent occupies the lower energy equatorial position of a boat-like transition state which places the bulky dialkylaluminum moiety away from the iron ligands. Possible transition states for the other observed diastereomeric products are also illustrated. 

The diastereoselectivity of the copper enolate 2b may be rationalized by suggesting that the chair-like cyclic transition state J is preferred which leads to the major diastereomer 4. The usual antiperiplanar enolate geometry and equatorial disposition of the aldehyde substituent are incorporated into this model. Possible transition states consistent with the stereochemistries of the observed minor aldol products are also illustrated. 

The diastereoselectivity observed can be explained by a synclinal transition state, probably influenced by chelation and/or stereoelectronic effects of the developing cation38. The minor product is formed via an antiperiplanar transition state. All compounds obtained are useful precursors for several spirocyclic natural products, such as terpenes like lubimine or acoradi-ene. 

In general, the Henry reaction proceeds in a non-selective way to give a mixture of anti (erythro) and syn (threo) isomers. Ab initio calculations on the Henry reaction suggest that free nitronate anions (not influenced by cations) react with aldehydes via transition states in which the nitro and carbonyl dipoles are antiperiplanar to each other. This kind of reaction yields anti-nitro alcohols. The Henry reaction between lithium nitronates and aldehydes is predicted to occur via cyclic transition states yielding syn-nitro alcohols as major products (Eq. 3.64).108... 

Here the P-hydrogen and the chlorine are both axial. This allow an antiperiplanar transition state. 

The stereoselectivity proved to be dependent on the nature of the halide ligand X and was found to be complete for X = Br. Reversal of the diastereoselectivity from anti to syn has been accomplished by adding Et2OBF3 [37]. The predominant syn selectivity in the presence of this Lewis acid is consistent with a non-cyclic antiperiplanar transition state. 

There are two other mechanistic possibilities, halogen atom abstraction (HAA) and halonium ion abstraction (EL), represented in Schemes 4.4 and 4.5, respectively, so as to display the stereochemistry of the reaction. Both reactions are expected to be faster than outer-sphere electron transfer, owing to stabilizing interactions in the transition state. They are also anticipated to both exhibit antiperiplanar preference, owing to partial delocalization over the C—C—Br framework of the unpaired electron in the HAA case or the electron pair in the EL case. Both mechanisms are compatible with the fact that the activation entropies are about the same as with outer-sphere electron donors (here, aromatic anion radicals). The bromine atom indeed bears three electron pairs located in two orthogonal 4p orbitals, perpendicular to the C—Br bond and in one s orbital. Bonded interactions in the transition... 

Chiral allenyltitanium reagents, prepared from propargylic phosphates as outlined, react with alkylidene malonates to afford 1,4-adducts with excellent anti dia-stereoselectivity (Table 9.26) [42]. The addition is presumed to take place through an open antiperiplanar transition state (Scheme 9.12). 

Roth and coworkers23 reported NMR data of the orthogonal butadiene (Z,Z)-3,4-dimethylhexa-2,4-diene. (Z,Z)-13 having the planes of the double bonds at a dihedral angle not far from 90°. This diene serves as the model for conjugated diene lacking rr-electron delocalization and for the transition state for interconversion of antiperiplanar (trans) and synperiplanar (cis or gauche) butadiene. 

Darzens reaction of (-)-8-phenylmethyl a-chloroacetate (and a-bromoacetate) with various ketones (Scheme 2) yields ctT-glycidic esters (28) with high geometric and diastereofacial selectivity which can be explained in terms of both open-chain or non-chelated antiperiplanar transition state models for the initial aldol-type reaction the ketone approaches the Si-f ce of the Z-enolate such that the phenyl ring of the chiral auxiliary and the enolate portion are face-to-face. Aza-Darzens condensation reaction of iV-benzylideneaniline has also been studied. Kinetically controlled base-promoted lithiation of 3,3-diphenylpropiomesitylene results in Z enolate ratios in the range 94 6 (lithium diisopropylamide) to 50 50 (BuLi), depending on the choice of solvent and temperature. ... 

Ab initio methods using the 6-31 + G basis sets have been used in a theoretical study of competing, S n2 and El reactions of NCCH2CH2CI with HO and HS in the gas phase. The antiperiplanar elimination transition state, which is favoured over those for n2 and El(gauche) reactions, is more lcB-like than that for the slower El anti) reaction of ethyl chloride. 

The results suggest that competition between antiperiplanar and synclinal transitions... 

This is attributed to the unfavourable steric interactions which arise in the transition state that is required for antiperiplanar migration of the exocyclic substituent.143 Some examples of synthesis of alcohols by hydroboration-oxidation are included in Scheme 4.8. More vigorous oxidizing agents such as Cr(VT) reagents effect replacement of boron... 

It remains to explain why the Felkin transition states are the most stable. During the reaction, the major interaction occurs between the nucleophile s HOMO and the substrate s LUMO. Therefore, the most reactive conformation of the substrate is that with the lowest LUMO. This corresponds to the geometry in which the C2-L bond is parallel to the tt system, as there is then a good overlap between the orbital and the lowlying ac2-L orbital, leading to a stabilization of the LUMO. The nucleophile may attack this conformer in an antiperiplanar or synperiplanar stereochemistry. The latter is disfavoured for two reasons ... 

If this interpretation is correct, then in any reaction with asymmetric induction, a search for antiperiplanarity between the incipient bond (Nu-Cl) and an adjacent sigma bond (C2-L) should lead to the most favourable transition states, all other things being equal. Let us apply this rule to the so-called product development control problem. Consider a conformationally fixed cyclohexanone, for example 14. 

Finally, it should be mentioned that Suzuki et al. have aheady remarked the correlation existing between ketone flexibility and axial attack. Vails, Toromanoff and Mathieu have also underlined the importance of antiperiplanar attack, although their interpretation is different from ours and stresses the low energy content of the pre-chair transition state. 

A different kind of closed five-membered transition state has been postulated in 5-e.vo-trig radical13 and metallo-ene14 cyclizations. In both cases simple diastereoselection is effected via similar transition states (36 and 42) in which the exocyclic appendages adopt antiperiplanar arrangements with respect to the endocyclic C-C bonds (C-2/3 and C-3/4). Thus, the appendages are in the cis orientation on the newly formed rings 37/38 and 43/44. 

The preferred transition state can be described as depicted in 954,57 with the electrophile approaching antiperiplanar to the perpendicularly disposed Z substituent [Si(CH3)2C6H5]. 

It appears likely that the reaction proceeds through the ene reaction pathway, although such an ene reaction pathway has not been previously recognized as a possible mechanism in the Mukaiyama aldol reaction. In general, an acyclic antiperiplanar transition-state model has been used to explain the formation of the syn-diastereomer from either ( )- or (Z)-silyl enol ethers [58]. However, the cyclic ene mechanism now provides another rationale for the. vyra-diastereose-lection regardless of the enol silyl ether geometiy (Figure 8C.7). 

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