Chairlike transition state

These reactions will be discussed in more detail under the topic of 3,3-sigmatropic rearrangements in Chapter 11. For the present we simply want to focus on the fact that the reaction is stereospecific-, the -isomer gives one diastereomeric product whereas the related Z-isomer gives a different one. The stereochemical relationship between reactants and products can be explained if the reaction occurs through a chairlike transition state in... 

According to this concept, the aldol condensation normally occurs through a chairlike transition state. It is further assumed that the stmcture of this transition state is sufficiently similar to that of chair cyclohexane to allow the conformational concepts developed for cyclohexane derivatives to be applied. Thus, in the example above, the reacting aldehyde is shown with R rather than H in the equatorial-like position. The differences in stability of the various transition states, and therefore the product ratios, are governed by the steric interactions between substituents. 

The transition state for such processes is represented as two interacting allyl fragments. When the process is suprafacial in both groups, an aromatic transition state results, and the process is thermally allowed. Usually, a chairlike transition state is involved, but a boatlike conformation is also possible. 

The Cope rearrangement usually proceeds through a chairlike transition state. The stereochemical features of the reaction can usually be predicted and analyzed on the basis of a chair transition state that minimizes steric interactions between the substituents. Thus, compound 26 reacts primarily ttuough transition state 27a to give 28 as the major product. Minor product 29 is formed flirough the less sterically favorable transition state 27b. 

The stereochemical features of the Claisen rearrangement are very similar to those described for the Cope rearrangement, and reliable stereochemical predictions can be made on the basis of the preference for a chairlike transition state. The major product has the -configuration at the newly formed double bond because of the preference for placing the larger substituent in the pseudoequatorial position in the transition state. ... 

Lewis acids, results in the formation of isopulegol (43) with greater than 98% diastereoselectivity isopulegol (43), wherein all of the ring substituents are equatorially oriented, arises naturally from a chairlike transition state structure in which the C-3 methyl group, the coordinated C-l aldehyde carbonyl, and the A6,7 double bond are all equatorial (see 48). A low-temperature crystallization raises the chemical and enantiomeric purity of isopulegol (43) close to 100%. Finally, hydrogenation of the double bond in 43 completes the synthesis of (-)-menthol (1). 

Once again, desilylation and oxidative cleavage33 delivers the hydroxycarboxylic acids. A chairlike transition state model, analogous to that proposed for the corresponding boron enolate33, is postulated in order to rationalize the ul topicity of the above titanium enolate. 

The stereochemical outcome of the reaction of 1-43, formed from 1-40 by desily-lation, can be explained by assuming a pseudoequatorial orientation of the epoxide moiety in a pseudo-chair-chairlike transition state 1-44 which, after being attacked by the phenolic oxygen, furnishes the correct trans-fused stereoisomer 1-41 (Scheme 1.12). The conformation 1-45, which would lead to 1-46 seems to be disfavored. 

The use of ( )-enolcarbamates of type 1-56 allowed the generation of tetrahy-dropyrans 1-58 with complementary orientation of the carbamate functionality (Scheme 1.15). In all cases, the carbamate group adopts an axial orientation in the chairlike transition state 1-57. 

In an extensive investigation of the stereochemical memory effect, a series of six diastereomeric pairs of substrates was prepared to probe the effect of single, then multiple substituents on the 5-exo cyclization of amines onto alkene radical cations [144,145]. Overall, these cyclizations were highly dia-stereoselective and were accounted for by a transition-state model employing a chairlike transition state with attack of the nucleophilic amine on the opposite face of the alkene radical to the one shielded by the phosphate anion in the initial contact ion pair (Scheme 34), as exemplified in Schemes 35 and 36. 

The transition-state model for these cyclizations (Scheme 34) differs fundamentally from the well-established Beckwith-Houk transition model for radical cyclizations [130,146-148]. Thus, while both models invoke chairlike transition states, without excluding the possibility of twist boatlike systems in some instances, the Beckwith-Houk model involves full conformational... 

Scheme 34 Chairlike transition-state model for cyclization in a contact ion pair...

The enantioselectivity in these reductions is proposed to arise from a chairlike transition state in which the governing steric interaction is with the alkyl substituent on boron.99 100 There are data indicating that the steric demand of this substituent influences enantioselectivity.101... 

Because of the concerted mechanism, chirality at C-3 (or C-4) leads to enantiospecific formation of new chiral centers at C-l (or C-6).138 These relationships are illustrated in the example below. Both the configuration of the new chiral center and that of the new double bond are those expected on the basis of a chairlike transition state. Because there are two stereogenic centers, the double bond and the asymmetric carbon, there are four possible stereoisomers of the product. Only two are formed. The /i-double-bond isomer has the S-configuration at C-4 whereas the Z-isomer has the -configuration. These are the products expected for a chair transition state. The stereochemistry of the new double bond is determined by the relative stability of the two chair transition states. Transition state B is less favorable than A because of the axial placement of the larger phenyl substituent. 

The mechanism and stereochemistry of the ortho ester Claisen rearrangement are analogous to those of the Cope rearrangement. The reaction is stereospecific with respect to the double bond present in the initial allylic alcohol. In acyclic molecules, the stereochemistry of the product can usually be predicted on the basis of a chairlike transition state.158 When steric effects or ring geometry preclude a chairlike structure, the reaction can proceed through a boatlike transition state.159... 

A number of steric effects on the rate of rearrangement have been observed and can be accommodated by the chairlike transition-state model.165 The A-silyl enol ethers... 

The E/Z stereoselection can be rationalized by assuming metal-centered pericyclic chairlike transition states 1 13,10 , 12 and 13. In this model proton transfer and metal ion transfer are assumed to occur simultaneously. When R is a bulky group, the nonbonded steric interaction between this group and the methyl group becomes strong and the Z-enolate will be the predominating isomer under kinetic control. 

Yttrium-catalyzed enyne cyclization/hydrosilylation was proposed to occur via cr-bond metathesis of the Y-G bond of pre-catalyst Cp 2YMe(THF) with the Si-H bond of the silane to form the yttrium hydride complex Ig (Scheme 8). Hydrometallation of the C=G bond of the enyne coupled with complexation of the pendant G=G bond could form the alkenylyttrium alkyl complex Ilg. Subsequent / -migratory insertion of the alkene moiety into the Y-C bond of Ilg could form cyclopentylmethyl complex Illg. Silylation of the resulting Y-C bond via cr-bond metathesis could release the silylated cycloalkane and regenerate the active yttrium hydride catalyst. Predominant formation of the /ra //j--cyclopentane presumably results from preferential orientation of the allylic substituent in a pseudo-equatorial position in a chairlike transition state for intramolecular carbometallation (Ilg —IHg). 

Yttrocene complexes catalyze the cascade cyclization/hydrosilylation of trienes to form saturated silylated bicyclic compounds.For example, reaction of the 4-silyloxy-4-vinyl-l,6-hexadiene 69 and phenylsilane catalyzed by Gp 2YMe(THF) at room temperature for 1 h followed by oxidation of crude 70a gave [3.3.0]bicyclic diol 70b in 73% yield over two steps as a single diastereomer (Scheme 18). Selective conversion of 69 to 70a presumably requires initial 1,2-hydrometallation of one of the less-hindered G=G bonds to form alkylyttrium alkene complex II (Scheme 18). Selective S-exo carbometallation of II in preference to -exo carbometallation would form cyclopentyl-methylyttrium complex III (Scheme 18). Gyclization of III via a chairlike transition state would form the strained /r< /75 -fused alkylyttrium complex IIIl, which could undergo silylation to form 70a. 

Yttrium-catalyzed cascade cyclization/hydrosilylation of 3-(3-butynyl)-l,5-hexadienes was stereospecific, and syn-19 (R =Gy, R = OGPh3) underwent cascade cyclization/hydrosilylation to form 80b (R = Gy, R = OGPh3) in 97% yield as a single diastereomer (Scheme 20). The regio- and stereoselective conversion of syn-19 to 80b was proposed to occur through an initial 5- x -intramolecular carbometallation via a chairlike transition state that resembles alkenyl olefin eomplex syn- m. followed by S-exo intramolecular carbometallation via a boatlike transition state that resembles alkyl olefin complex boat-llm. The second intramolecular carbometallation presumably occurs via a boatlike transition state to avoid the unfavorable 1,3-interaction present in the corresponding chairlike transition state (Scheme 20). 

Pd(II)-catalyzed Cope rearrangement [225] occurs at room temperature, via chairlike transition states. A plausible mechanism is cyclization-induced rearrangement. Both the addition and fragmentation steps are assisted by the introduction and removal... 

The process is a [3,3]-sigmatropic rearrangement with a chairlike transition state. 

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