Antiperiplanar

The relative eonfiguration C is derived from the eoupling eonstants of the H NMR speetrum the 11.9 Hz coupling of the phenyl-C//proton [Sh = 3.36) proves its antiperiplanar relationship to the... 

The CH fragment which is linked to the OH group (Sh = 5.45 ) can easily be located in the H and NMR spectra. The chemical shift values Sc =74.2 for C and Sh = 3.16 for //are read from the CH COSY plot. The H signal at S,i = 3.16 splits into a triplet (11.0 Hz) of doublets (4.0 Hz). The fact that an antiperiplanar coupling of 11 Hz appears twice indicates the diequatorial configuration (trans) of the two substituents on the cyclohexane ring 5. If the substituents were positioned equatorial-axial as in 4 or 5, then a synclinal coupling of ca 4 Hz would be observed two or three times. 

The relative configuration of the protons follows from the Jhh coupling constants, of which it is necessary to concentrate on only two signals (at Sh = 4.88 and 2.41). The proton at Sh = 4.88 shows a quartet with a small coupling constant 3 Hz) which thus has no antiperiplanar relation-... 

The anomeric effect is also present in acyclic systems and stabilizes conformations that allow antiperiplanar (ap) alignment of the C—X bond with a lone-pair orbital of the heteroatom. Anomeric effects are prominent in determining the conformation of acetals and a-alkoxyamines, as well as a-haloethers. MO calculations (4-3IG) have found 4kcal/mol as the difference between the two conformations shown below for methoxy-methyl chloride. ... 

The synclinal conformation (sc) is appropriate for overlap of an oxygen nonbonded pair with the a C—Cl orbital. The preferred ap relationship, requires an antiperiplanar alignment of a lone-pair orbital with the bond to the electronegative substituent. Because of the donor-acceptor nature of the interaction it is enhanced in the order F < O < N for the donor (D) atom and N < O < F for the acceptor (A) atom. 

The preferred conformation is D because it maximizes the number of antiperiplanar relationships between nonbonded electron pairs and C—O bonds while avoiding the R -R van der Waals repulsions in conformations E and F. 

In cyclic systems such as 1, the dominant conformation is the one with the maximum anomeric effect. In the case of 1, only conformation lA provides the preferred antiperiplanar geometry for both oxygens. Antiperiplanar relationships are indicated by including lone pairs in the oxygen orbitals. Other effects, such as torsional strain and nonbonded repulsion, contribute to the conformational equilibrium, of course. Normally, a value of about 1.5 kcal/mol is assigned to the stabilization due to an optimum anomeric interaction in an acetal. 

Another example of a stereoelectronic effect is observed in amines. Amines in which a C—H bond is oriented antiperiplanar to the nitrogen lone pair show a shift in the C—H bond stretching frequency that corresponds to a weakening of the bond by about... 

Bohlmann et al. (118-121) observed that an infrared absorption band between 2700-2800 cm is characteristic of a piperidine derivative possessing at least two axial carbon-hydrogen bonds in antiperiplanar position to the free-electron pair on the nitrogen atom. The possibility of forming an enamine by dehydrogenation can be determined by this test. Compounds which do not fulfill this condition cannot usually be dehydrogenated (50, 122,123). Thus, for example, yohimbine can be dehydrogenated by mercuric acetate,whereas reserpine or pseudoyohimbine do not react (124). The quinolizidine (125) enamines (Scheme 4), l-azabicyclo(4,3,0)-nonane, l-azabicyclo(5,3,0)decane, l-azabicyclo(5,4,0)undecane, and l-azabicyclo(5,5,0)dodecane have been prepared in this manner (112,126). 

The dehydration reaction leads by an Ea process to 8 and is promoted by the tertiary, benzylic nature of the OH group at Ce and its antiperiplanar trans relationship to the H atom at Csg. Furthermore, one of the cannonical forms of the enolizable 0-dicarbonyl system present at Cn and Cia has a double bond in the C ring. Thus, dehydration leads to aromatization of the C ring, and this factor must provide some of the driving force for the reaction. 

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. 

It is interesting to speculate that asymmetric induction may be the consequence of the exo anomeric effect, a stereoelectronic effect that favors the conformation 5 that places the aglycone O-C bond antiperiplanar to the pyran C(1) —C(2) bond7fi. Related asymmetric induction has also been observed in aldehyde addition reactions of the related, but racemic, pinacol (Z)-y-(tetrahydropyranyloxy)allylboronate49. As indicated in the examples above, however, the level of diastereoselectivity is modest and the only application in asymmetric synthesis is Wuts exo-brevicomin synthesis75. 

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

Trimethyl(l-phenyl-2-propenyl)silane of high enantiomeric excess has also been prepared by asymmetric cross coupling, and reacts with aldehydes to give optically active products in the presence of titanium(IV) chloride. The stereoselectivity of these reactions is consistent with the antiperiplanar process previously outlined75. 

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. 

With l-alkyl-3-alkoxyallylstannanes, effective asymmetric induction occurs to give (E)-syn-products consistent with an antiperiplanar, antarafacial S t process. The optical purity of the products parallels that of the stannane106. 

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. 

These results may be explained either by Cram s cyclic model in the case of lithium alkyls or by Cornforth s dipolar model if copper-boron trifluoride reagents are used. Boron trifluoride causes double complexation of both nitrogen and oxygen atoms which results in the formation of an adduct with rigid antiperiplanar conformation due to electrostatic repulsion (see 4 and 5)9. 

Phenyllithium and phenylcopper boron trifluoride yield different diastereomers of the reaction products, i.c., the sense of asymmetric induction is a function of the metal. These results are rationalized on the basis of antiperiplanar 6 and synperiplanar 8 reactive enoate conformations for additions of the copper and lithium reagents, respectively. 

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. 

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