Boatlike transition state

The products corresponding to boatlike transition states are usually not observed for acyclic dienes. However, the boatlike transition state is allowed, and if steric factors make a... 

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... 

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). 

The proposed mechanism of reduction3337 involves the coordination of a borane molecule to the nitrogen of the oxazaborolidine in a trans-relationship to the indanyl substituent. The ketone coordinates to the boron center of the oxazaborolidine, cis to the coordinated borane, in a possible boatlike transition state 20 or chairlike transition state 21 (Figure 17.3). In both cases, intramolecular hydride attack occurs from the Re-face of the carbonyl. 

A chairlike transition state is favored over a boatlike transition state. There are, however, exceptions. 

Although a chairlike transition state is favored for the Claisen rearrangement reactions of acyclic substrates, this is not always the case with cyclic systems. For example, Bartlett and Ireland independently studied the rearrangement reactions of cyclohexenyl silylketeneacetals and found that there was competition between the chairlike and boatlike transition states11 (Scheme l.VII). Clearly, the -isomer IE gives 8a via a chairlike transition state, whereas the Z-isomer 7Z affords the same product (8a) via a boatlike transition state. 

For the reaction of 7 (OMe), chairlike transition state A is favored over boatlike transition state B12 (Scheme l.IX). These computational results provide a solid theoretical rationalization of the original proposal by Bartlett and Ireland that the boatlike transition state is favored for the Claisen rearrangement of 7Z, and the chairlike transition state is preferred for IE. 

A number of theoretical studies have been conducted to understand the mechanism of the Cope rearrangement.16 According to calculations by Houk and co-workers, the chairlike transition state is more stable than the boatlike transition state by 7.8 kcal/mol (Scheme l.XII). When Schleyer and colleagues performed calculations to compute the magnetic properties of the transition-state structures, transition states A and B had a magnetic susceptibility of—55.0 and—56.6, respectively. These values are comparable to that of benezene (—62.9), confirming the existence of an aromatic transition state in the Cope rearrangement. 

One classic example is an experiment reported by Doering and Roth in 196217 (Scheme 1.XIII). Upon heating, racemic 3,4-dimethylhexa-l,5-diene (13) rearranged to a mixture of (2 ,6 )-octa-2,6-diene (90%), (2Z,6Z)-octa-2,6-diene (9%), and a trace amount of (2 , 6Z)-isomer. The experimental results are explained in terms of a six-membered transition state17 (Scheme 1.XIV). Chairlike transition state A is favored over transition state B based on the conformational analysis of 1,2-dimethylcyclohexane, in which the methyl substituents prefer to be in an equatorial position. The observation that 14 Z was formed in only trace amounts indicates that boatlike transition state C is of significantly higher energy than transition state A or B. 

The preference for a chairlike transition state in the Johnson-Claisen rearrangement is supported by further Houk et al. s computational studies (Scheme 1.2e).5 For the rearrangement of the parent methyl ketene acetal, chairlike transition state A is favored over boatlike transition state B by 2.3 kcal/mol. 

Based on the accompanying kinetic data and an observation that lithium cation is essential in the lithium aluminum hydride reduction,5 Ashby and Boone proposed that the reduction would occur via a six-membered transition state in which the lithium cation is involved4 (Scheme 4.II). Because the aluminum in the boat transition state TS-boat is proximal to the carbonyl oxygen, the boat transition state might be of lower energy than the chairlike transition state TS-chair. Furthermore, the boatlike transition state would be a favored states as it results in direct formation of the lithium alkoxyaluminum hydride intermediate. 

Danishefsky and coworkers have demonstrated the conversion of lactones to carbocycles by the 3,3-sigmatropic shift of silylketene acetals. Jq the total synthesis of the Fusarium toxin equisetin, for example, keto lactone (138) was converted to its bissilyl derivative (139) by reaction with 2 equiv. of LDA and an excess of TMS-Cl. In situ thermolysis of ketene acetal (1 ) led to a very smooth transformation into ester (140), which was carried on to equisetin (Scheme 26). This methodology was also applied by Schreiber and Smith in the preparation of the cyclohexyl moiety of the immunosuppressive agent FK-506. Ireland-Claisen rearrangement of silylketene acetal (142), prepared by treatment with TBDMS-OTf and triethylamine at low temperature, provided, after hydrolysis of the silyl ester, the carboxylic acid (143) in 71% overall yield (Scheme 27). The strict translation of configuration via a boatlike transition state is typical for this permutation. 

Although chorismate mutase does provide a rate enhancement of 2 X 10 (147), this uni-molecular reaction readily occurs without enzyme, under mild conditions. The reaction was expected to pass through a chairlike transition state (59)(Fig. 17.25) but early molecular orbital calculations indicated that the boatlike transition state (60) was not out of the question (147). In an attempt to define the transition-state structure, several compounds, each designed to mimic a putative transition state, were synthesized and tested as chorismate mutase inhibitors (147). The enzyme was found to be inhibited by the exo-carboxy nonane (61), with an apparent value of 3.9 X 10 M Conversely, the endo-carboxy nonane (62) did not inhibit the enzyme. The apparent K- value of the adaman-... 

The overall reaction amounts to a transposition of the initial alkene double bond. In contrast to ring opening of epoxides by nucleophiles, the base-induced elimination requires a non-nucleophilic strong base, such as a lithium dialkylamide (e.g., LDA). The reaction is believed to proceed via a yn-elimination involving a boatlike transition state. ... 

In acyclic systems the Claisen-lreland rearrangement proceeds via a chairlike transition state (TS). However, iri cyclic systems conformational constraints can override the inherent preference for chairlike TS and the boatlike TS becomes dominant. One explanation for the preference of boatlike transition states in cyclic systems is the destabilizing steric interactions of the silyloxy substituent and the ring atoms in a chairlike TS. ... 

Due to conformational constraints in some cyclic substrates, a boatlike transition state may be... 

Ireland, R. E., Wipf, P., Xiang, J. N. Stereochemical control in the ester enolate Claisen rearrangement. 2. Chairlike vs boatlike transition-state selection. J. Org. Chem. 1991, 56, 3572-3582. 

Figure 2. Diagrammatic representations of the alternative transition state structures and some proposed analogs (a) chair-like transition state structure (b) boatlike transition state structure (c) exo-6-hydroxybicyclo (3.3.1) nonane-1,exo-3-dicarboxylic acid (d) exo-6-hydroxybicyclo (3.3.1) nonane-1,endo-3-dicarboxylic acid, (e) 6-hydroxyadamantane-l,3-dicarboxylic acid.

There are still two possibilities for the transition state, 22 and 23. In transition state 22, the Rh carbene is pointed away from the flip of the incipient cyclopentane ring (a chairlike transition state, counting the five carbons and the Rh in the six-membered ring), whereas in 23 the Rh carbene is pointed toward the flip of the incipient cyclopentane ring (a boatlike transition state). As 10 (Scheme 3) cyclizes to 12, in which the methyl and the phenyl are on the same face of the cyclopentane, we concluded that at the point of commitment to product formation, the transition state leading to cyclization must be chairlike (22) rather than boatlike (23). 

Under kinetic control, the reactions of prochiral aldehydes with Z-enolates generally lead to syn aldols, while E-enolates lead to anti aldols. The presence of bulky R groups on the enolates, however, may alter these selectivities. The highest diastereoselectivities are observed with boron or titanium enolates. These selectivity trends are interpreted by a concerted cyclic mechanism. The favored transition state resembles a distorted chair, in line with the Zimmermann-Traxler proposals [57, 160, 253] (Figure 6.70). This model has been supported by theoretical studies [9, 40, 41, 125, 1249], Transition states analogous to C2 and C4 (Figure 6.70) are destabilized by 1,3-ecIipsing interactions between the C-R, M-L and C-R bonds, so that models Ci and C3 are more favorable. For the sake of simplification, only the reaction on one face of the enolates is shown in these models, but enolate face selectivity will be discussed later. In some cases, boatlike transition-state models are invoked to interpret selectivity inversions [401, 402, 666], Moreover, Heathcock and coworkers [105] obtained evidence for the influence of an excess of n-B BOTf on the stereoselectivity of the aldol reactions of Z-enolates. In such reactions, anti aldols can be formed preferentially (see bdow). 

Relatively few studies of the reactions of allylboronates and ketones have appeared. The reaction of (85) and ethyl pyruvate, for example, was conducted under 6 kbar pressure at 45 C for 80 h to give a 9 1 mixture of diastereomers (86a) and (86b). The stereochemistry of this reaction parallels that seen with crotyl-9 BBN (Figure 10) in that the structure of the major isomer is consistent with a transition state in which the —C02Et unit adopts an equatorial position. The same result could occur, however, via a boatlike transition state with an axial —C02Et group. 

In acyclic Claisen systems, chairlike transition states are usually preferred. The preference for the chairlike transition state can be changed to a boatlike transition state in constrained cyclic systems. 

Dihydropyran rearrangements ( 1,4 rearrangements) proceed through the boatlike transition state, because the chairlike transition state which is constrained by a two carbon tether would lead to strained (Cl-cyclohexcne derivatives176. 

By a similar reaction, the cyclohexyl moiety of FK-506 (see p 3395), a macrolide antibiotic with potent immunosuppressive properties, was prepared from lactone 14. In this case, a boatlike transition state 15 has been suggested325. 

The boatlike transition state is also preferred over the chairlike in the rearrangement of 2,5-dihydrooxepins ( 1,6 rearrangements). The reaction sequence results in an overall four-atom ring contraction ( Claisen contraction ) 328,329. This methodology has been applied to the total synthesis of (— )-oc-kainic acid 330 331, alkaloidal building blocks332,333, and cis-chrysanthemic acid and esters334 (cf. p 3467). 

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