Six-membered chairlike transition state

A six-membered chairlike transition state was proposed in which the ( )-ketene silyl acetal is placed in the opposite direction to the oxazolidinone carbonyl to avoid dipole moment repulsion, with the allylic moiety oriented away from the hindered indane backbone. This transition state would account for the direction of the asymmetric induction and also explain the better results observed with smaller silylating groups (Figure 24.7).108... 

The stereochemical outcome can be rationalized by considering the approach of the aldehyde to the preferred conformation of the allylindium. The approach of the aldehyde is postulated to be in antiperiplanar to the OPG group as for the Felkin-Anh model. The allylindium prefers to adopt the conformation 12 rather than 13, where the 1,3-allylic strain with R is minimized and the steric interaction with the aldehyde is also reduced (Scheme 18). The facial selection with respect to the aldehyde is determined by the aldehyde residue (R ) to occupy in the least sterically demanding position, away from the substituted allylic carbon. The carbonyl allylation then proceeds via a six-membered chairlike transition state, in which the aldehyde substitutent attains an equatorial position, to afford the 1,4-syn product. 

In the following four chapters, readers will find some of the most frequently cited and most synthetically relevant examples of the Zimmerman-Traxler or six-membered transition state. In presenting reactions that go through a six-membered chairlike transition state, I pay special attention to including computational studies, in an effort to prove the existence of a six-membered chairlike transition state. Although not all six-membered transition states have been studied computationally, recent interest in using computers in studies of stereoselective reactions would certainly confirm the legitimacy of Zimmerman-Traxler transition states for many more reactions.5... 

For the rearrangement of 6, the major isomer is once again formed through six-membered chairlike transition state C3 (Scheme 1.5f). Because the methoxy substituent in transition state C is now in an axial position, the free-energy gap between transition states C and D becomes narrow, resulting in diminished 3 1 diastereoselectivity. 

Makino and others carried out a computational study on the Evans aldol reaction of dimethylborinate 12BMe2 with acetaldehyde7 (Scheme 2.1h). The AMI semiempirical calculations indicate that six-membered chairlike transition state A, which would lead to formation of the major syn-isomer, is more stable than B by 3.0kcal/mol, providing a theoretical confirmation of the experimental observations. 

The aldol reactions of the titanium Z-enolates proceeded smoothly with various aldehydes precomplexed with titanium chloride at -78° C. The diastereose-lectivity is high to excellent, with the single exception of benzaldehyde. The high degree of diastereoselection associated with this current asymmetric anti-aldol process can be rationalized by a Zimmerman-Traxler type of six-membered chairlike transition state Al9fl (Scheme 2.2r). The model is based on the assumptions that the titanium enolate is a seven-membered metallocycle with a chairlike conformation, and a second titanium metal is involved in the transition state, where it is chelated to indanolyloxy oxygen as well as to the aldehyde carbonyl in a six-membered chairlike transition-state structure. 

To explain the stereochemical outcome of the reaction of allylic boron reagents with carbonyl compounds, Houk and Li carried out calculations on the transition structures of the model reaction of formaldehyde and allylboronic acid6 (Scheme 3.V). The bimolecular complex formed initially between allylboronic acid and formaldehyde would rearrange via a six-membered transition state to form an intermediate. Calculations show that chair transition state A is 8.2kcal/ mol more stable than twist-boat transition structure B, clearly confirming that the six-membered chairlike transition-state model is a legitimate scheme to predict the stereochemical outcome of the boron allylation reaction. 

An interesting diastereoselectivity pattern was observed when a-halogen-sub stituted allylboronates were added to aldehydes. In this reaction, (Z)-alkenes were obtained as the major products7 (Scheme 3.VII). Hoffmann and Landmann explained the results by examining two competing six-membered chairlike transition states (Scheme 3.VIII). Among the possible factors that favor the transition state A, they pointed out that dipole-dipole interactions could play a dominant... 

The stereochemical outcome of the reaction above is explained in terms of a structurally rigid 1,3-bridged six-membered chairlike transition state (Scheme 3.2i). Transition state B would be disfavored relative to transition state A because the phenyl group of benzoin is engaged in nonbonded interactions with the methyl and the hydrogen of the crotylsilane. 

Asymmetric allylation and crotylation reactions using allylic trichlorosilanes and chiral phosphonamides were developed by Denmark and coworkers in 1994 and further refinement of the chiral ligands system was made in 200114 (Scheme 3.2k). The influence of the six-membered chairlike transition state is once again evidenced by the excellent correlation of the geometry of the reacting silanes with the diastereomeric composition of the products. Thus, anti -isomer is obtained from the -allylic silane, and syn-isomer is produced from the Z-silane. Based on... 

Noyori et al. proposed that the reaction would be initiated by complexation of the Lewis acidic lithium cation to the ketone oxygen atom then hydride transfer occurs from aluminum to the carbonyl carbon by way of a six-membered chairlike transition state3 (Scheme 4.3c). Between the two competing six-membered chairlike transition states A and B, transition state B is disfavored, due to the substantial n/it-type electronic repulsion between the axially oriented binaph-thoxyl oxygen and the unsaturated phenyl or alkenyl moiety. Although there is a 1,3-diaxial steric interaction between the Al-0 and C-R bonds in transition state... 

This book will serve as a starting point in learning the amazing features of six-membered chairlike transition states in stereoselective organic reactions. With this book, I hope that students and practitioners alike will be able to propose reasonable transition states for the description of newly discovered stereoselective reactions. 

The diastereoselectivity for the reaction of 157, which possesses a 2-methyl-1,3-dioxolanyl group, with enolates generated from fert-butyl acetate was found to be highly dependent on the reaction conditions.89 For example, the lithium enolate gave (Ss,S)-158 (72% de) while the titanium enolate afforded (Ss,/ )-158 (92% de). A non-chelation-controlled transition state was used to explain the preferential formation of (Ss,S)-158 while a six-membered chairlike transition state containing a four-membered metallocycle and/or a seven-membered counterpart was proposed for the formation of the (Ss,R)-158. Treatment of (Ss,S)-158 with TFA gave P-amino acid 159 in 70% yield. 

The originally proposed stereochemical model by Hajos and Parrish" was rejected by M.E. Jung and A. Eschenmoser. They proposed a one-proline aldolase-type mechanism involving a side chain enamine. The most widely accepted transition state model to account for the observed stereochemistry was proposed by C. Agami et al. suggesting the involvement of two (S)-(-)-proline molecules. " " Recently, K.N. Houk and co-workers reexamined the mechanism of the intra- and intermolecular (S)-(-)-proline catalyzed aldol reactions. Their theoretical studies, kinetic, stereochemical and dilution experiments support a one-proline mechanism where the reaction goes through a six-membered chairlike transition state. 

Both the oxidant carbonyl compound (acetone) and the substrate alcohol are bound to the metal ion (aluminum). The alcohol is bound as the alkoxide, whereas the acetone is coordinated to the aluminum which activates it for the hydride transfer from the alkoxide. The hydride transfer occurs via a six-membered chairlike transition state. The alkoxide product may leave the coordination sphere of the aluminum via alcoholysis, but if the product alkoxide has a strong affinity to the metal, it results in a slow ligand exchange, so a catalytic process is not possible. That is why often stoichiometric amounts of aluminum alkoxide is used in these oxidations. 

Spectroscopic and crystallographic studies of Reformatsky reagents derived from a-halo esters showed that the enoiate is present in the C-enolate form and in ether solvents they form dimers. Enolates derived from a-halo ketones prefer the O-metal enoiate form. It is assumed, based on theoretical calculation, that the zinc enoiate dimers are dissociated by the action of the carbonyl compound and converted to the corresponding O-zinc enolates. Subsequently, the reaction goes through six-membered chairlike transition state. 

A stereocontrolled total synthesis of (+)-vinblastine (329), a prominent alkaloid used in cancer chemotherapy, was reported by the Fukuyama/ Tokuyama team and features an INOC reaction for the preparation of a key reaction intermediate utilized in their synthesis (2010CR101). Thus, the oxidation of oxime 323 with sodium hypochlorite generated the expected nitrile oxide 324 which imderwent a subsequent 1,3-dipolar cycloaddition to produce isoxazoline 325 as a single isomer (Scheme 59). The INOC proceeded via a six-membered chairlike transition state (i.e., 324) to furnish 325 with the desired stereochemistry. After reductive cleavage of the N—O bond in isoxazoftne 325 with zinc dust in acetic acid, a... 

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