Antiperiplanar orientation

Much work has been done to determine sets of substituent effects in specific conformationally mobile or rigid frameworks, since a knowledge of such effects often furnishes valuable conformational information. For instance, it was concluded from yg- and 8-SCS values that substituents (X = OH, I) on the C(19) methyl group in some cholest-S-enes prefer an antiperiplanar orientation [X-C(19)H2-C(10)-C(1)] with respect to C(l) (81). In the following, SCS information for various classes of cyclic systems is discussed, with particular emphasis on configurational and conformational analysis. 

The initial step in the alternative hydrolysis mechanism is protonation of the ring 0i by Glu 35 (Scheme I). Cleavage of the endocyclic C1-O5 bond forms the acyclic oxocarbonium ion intermediate, which is stabilized by Asp 52. Attack by water, cleavage of the C1-O4 bond, and ring closure then lead to the observed products. Existing experimental data on lysozyme hydrolysis are consistent with Scheme I (see references in Post and Karplus ( )). Moreover, distortion of the ring in site D is not required and the antiperiplanar orientation of an exocyclic O4 lone pair orbital relative to the cleaved C1-O5 bond found in the simulation (see section on "Enhancement of a Substrate Conformation Optimum for Catalysis") is in accord with stereoelectronic requirements (1 ). ... 

The main steps in the currently accepted catalytic cycle of the Heck reaction are oxidative addition, carbopalla-dation (G=G insertion), and / -hydride elimination. It is well established that both, the insertion as well as the elimination step, are m-stereospecific. Only in some cases has formal /r/ / i--elimination been observed. For example, exposure of the l,3-dibromo-4-(dihydronaphthyloxy)benzene derivative 16 and an alkene 1-R to a palladium source in the presence of a base led to a sequential intra-intermolecular twofold Heck reaction furnishing the alkenylated tetracyclic products 17 in good to excellent yields (Scheme 9). " In the rate-determining step, the base removes a proton in an antiperiplanar orientation from the benzylic palladium intermediate. The best amine base was found to be l,4-diazabicyclo[2.2.2]octane, which apparently has an optimal shape for this proton abstraction. 

An attempt to study resolved (( )-18) as a probe for the detailed mechanism of the Adn—E vinylic substitution reaction has been complicated by intervention of a competing reaction route this is believed to involve a competing (ElcB elimination-addition, for which antiperiplanar orientation of H and Cl is not a requirement.7 a-Deuterated (ca 50%) E- and Z-substitution products (which do not themselves exchange deuterium) are obtained on reaction with MeS in 9 1 CD3CN-D2O but no incorporation of deuterium in unreacted ((/r)-18) occurs and neither does isomerism to ((Z)-18) precede elimination. 

The P-addition of alkyl radicals to 4-methyl-2-(arylsulfinyl)-2-cyclopentenone 117 has been shown to occur in a completely stereocontrolled manner. Of a mixture of (4/ )- and (45)-117, only (4R)-117 reacts with t-Bu and i-Pr radicals to give the trans adducts 119a and 119b in 99% yield, while (45)-117 remained entirely unreacted. The stereochemical outcome of the reaction shows that the alkyl radical approaches from the side opposite to the aryl moiety in an antiperiplanar orientation to the carbonyl and sulfoxide bond. The 2,4,6-triisopropylphenyl group on sulfur plays a critical role, as it effectively shields the olefin face at the P-position by one of the isopropyl groups. This was confirmed by the 1 1 diastereomeric mixture obtained in the reaction of 4-methyl-2-(p-tolylsulfmyl)-2-cyclopentanone with the tert-butyl radical. 

The MgBr2-promoted additions to the (5)-a-benzyloxy aldehyde proceed via a chelation-controlled transition state (Fig. 18). Approach to the carbonyl face of the nearly planar five-membered magnesium chelate is directed by the methyl substituent resulting in re attack by the allenylstannane through the antiperiplanar geometry for the (P) stannane and the synclinal geometry for the (M) stannane. An antiperiplanar orientation of the (A/) stannane would place the vinylic methyl substituent in close proximity to the chelate ring. 

There are emerging examples in which dppf functions as a unidentate ligand. This coordination mode has been postulated as the key intermediate in some catalytic processes (see Sect. 1.5.2.1). Diphosphines acting as a unidentate ligand were once thought to be unstable based on entropy arguments. In this mode of coordination, the expected antiperiplanar orientation of the pendant phosphine is rarely observed. The approximate anticlinal (eclipsed) conformation of most known unidentate complexes (t 122 — 123°) [42, 47, 51, 53] possibly reflects the higher influence of the... 

In their 2001 paper, the authors assume that transition state B is the favored transition state leading to the syn product. In that transition state, the carboxenium double bond and the crotyl silane double bond adopt a antiperiplanar orientation. However, the more recent theoretical paper by Tietze et al. suggests that the eclipsed transition state A explains the enhanced diastereoselectivity. 

Reactions of chiral allenes proceed with a preference for the formation of the syn diastereomer. The stereochemical outcome of these reactions can be rationalized by invoking an open transition state model for the addition reactions (Figure 12), which depicts an antiperiplanar orientation of the chiral allenylsi-lane to the aldehyde carbonyl. In this model, steric repulsion between the allenyl methyl and the aldehyde substituent is most likely responsible for the destabilization of transition state (B), which leads to the anti (minor) stereoisomer. This destabilizing interaction is minimized in transition state (A). Table 5 illustrates representative examples and summarizes the scope of the regiocontrolled synthesis of homopropargylic alcohols using allenylsilanes. 

Allylation reactions can be designed to effect high stereoselectivity in the case of chiral /3-alkoxy aldehydes, in which the ether oxygen provides for effective coordination with a Lewis acid. Multi-valent, oxophilic Lewis acids serve to pre-organize the aldehyde substrate in a six-membered chelation complex. As in the examples of a-chelation control, an open transition state is deployed with synchnal or antiperiplanar orientations based upon the consideration of steric interactions with placement of the small (hydrogen) vinyl substituent of the allylic stannane over the preformed metallocycle. Several examples are illustrated in Scheme 5.2.20. i... 

Sulfurane 1 reacts with a variety of diols to yield cyclic ethers the most efficient transformations involve formation of epoxides and oxetanes. This process occurs via an intramolecular SN2 mechanism and, thus, is only possible for 1,2-diols that can exist in an antiperiplanar orientation. Eschenmoser successfully deployed this strategy to form epoxide 27 fromdiol 26.10... 

A frequently invoked interaction is between a lone pair (LP) orbital as the filled orbital and a a or n orbital one bond removed as the vacant one. A large //,y value requires antiperiplanar orientation of the lone pair and the symmetry axis of the a orbital (the Y—A bond), as shown in [3], Which of... 

P3uimidines 75 exist in solution as mixtures of (E)- and (Z)-isomers in all cases the (E)-isomer predominates. The conformation of the (El-isomer of 7a (R=CH2COOMe) was determined from the heterocoupling constant between the methylidene proton and the C-atom of the ester, "7c-h=4.5 Hz, while H-NMR spectra show the antiperiplanar orientation of protons in the NHCH structural element in both (E)-isomers (/nhch=12.6-13.4 Hz) and (Z)-isomers (/nhch=13 0-14.5 Hz). 

The origin of this gauche attractive effect, which overcomes unfavorable steric and/or dipolar interactions, can be rationalized in terms of a a (or n ff ) energy-lowering orbital interactions between the best combinations of donor and acceptors bonds (or lone pairs of electrons) in an antiperiplanar orientation (Scheme 19) (73TL1645, 77]A8379, 79JA1700). 

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