Houk transition state model

Beckwith pioneered the use of a Thiol-Oxygen-Co-Oxidation (TOCO) process for the transformation of 1,4-dienes and 1,3,6-trienes to 1,2-dioxolanes [90], As illustrated by the example in Scheme 51 [90a], this process involves phenylthio radical addition to the least substituted double bond, oxygen entrapment, peroxyl radical cyclization, oxygen entrapment and hydrogen atom transfer from the thiol. In accord with the Beckwith-Houk transition state model [91, 92], cyclization provides preferentially the c/s-3,5-disubstituted 1,2-dioxolanes. 

Figure 4.17 Chair-like (Beckwith—Houk) transition-state model.

The enantioselectivity of a closely related reaction, the proline-catalyzed a-ami-nation of aldehydes with diazodicarboxylic esters, independently disclosed by List and by Jprgensen in 2002 [30], can also be accounted for by a List-Houk transition state model (Figure 2.10). 

The proline-catalyzed intermolecular Michael reaction of unactivated ketones with nitroalkenes [33] can also be fitted in a mechanistic scenario involving the List-Houk transition state model (Figpre 2.11). 

To overcome the lack of diastereoselectivity, Anderson et al. used the Houk transition state model to rationalise that increased steric bulk would... 

Eksterowicz J. E., Houk K. N. Transition-State Modeling With Empirical Force Fields Chem. Rev. (Washington, D. C.) 1993 93 2439-2461... 

Scheme 12.19. Transition state models for cyclization based on the work of Spellmeyer and Houk.

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... 

Eksterowicz, J. E. and Houk, K. N. 1993. Transition-state Modeling with Empirical Force Fields , Chem. Rev. 93, 2439. 

Synopsis of Goldfuss and Houk (1998) Origin of Enantioselectivities in Chiral /i-Arnino Alcohol Catalyzed Asymmetric Additions of Organozinc Reagents to Benzaldehyde PM3 Transition State Modeling . 

In contrast, when 6-exo cyclizations are effected in the presence of an ot-alkoxy or a-silyloxy substituent, the stereocontrol can be excellent, as has been observed in a Si-tethered cyclization of 54a (Scheme 15) where a single diastereomeric product was obtained [134]. In this case, additional conformational constraints aided the cyclization, as became evident upon finding that the product configuration was inconsistent with the standard Beckwith-Houk chair-equatorial transition state model. For 54a there are two chairlike conformations (chair-equatorial and chair-axial) conceivably leading to cyclization the latter has the C-O and C=N bonds in an anti relationship to minimize dipole repulsion (Scheme 15). The... 

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. 

Houk and Li also performed calculations on the reaction between allylboronic acid and acetaldehyde6 (Scheme 3.VI). Transition state A, in which the methyl group of acetaldehyde occupies an equatorial position is more stable than transition state B by 5.5kcal/mol. Thus, the theoretical studies support the transition-state models in Scheme 3.IV proposed by Hoffmann and others. 

Fio. 4. Houk s transition state model (a) and the Felkin-Ahn transition state model (b) for the reaction of the dioxolane (48) with nitrile oxides. 

In the course of a sulfonium ylide rearrangement a maximum munber of three stereogenic units can be generated (Scheme 87). The resulting homoal-lylic sulfide 354 contains up to two stereogenic centers and one stereogenic double bond. Based on the work of Houk [204] with R = H, the following simphfied transition-state models can be discussed (Scheme 88). 

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. 

Norrby, P.-O., Rasmussen, T., Haller, J., Strassner, T., Houk, K. N. Rationalizing the Stereoselectivity of Osmium Tetroxide Asymmetric Dihydroxylations with Transition State Modeling Using Quantum Mechanics-Guided Molecular Mechanics. J. Am. Chem. Soc. 1999, 121, 10186-10192. 

The addition of (219) to ,j8-dialkoxynitrones (220) can be rationalized by assuming a transition state model A (Figure 2) similar to that involved in nucleophilic addition to C= (Houk model) <82JA7162>. The reversal of stereoselectivity induced by diethyl aluminum chloride is consistent with a j8-chelation model B. The scope and the synthetic utility of these reactions have been amply demonstrated <95MI 306-01 >. 

Two reaction mechanisms have been proposed for these dihydroxylations (pathway a or b, Figure 7.23), either a concerted [3+2] cycloaddition of the olefins on osmium-diamine complex 7.33 or a stepwise reversible [2+2] cycloaddition followed by a rearrangement [559,1350], An X-ray crystal structure of the resulting osmic ester 2.89A shows its symmetrical structure. Houk s calculations [1351] are in favor of a concerted reaction, and his transition state model is reactant-like, with steric interactions dictating the face selectivity of osmylation. 

Eksterowicz JE, Houk KN. Transition-state modeling with empirical force fields. Chem... 

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