Transition Houk-List

Thus, a unified model for proline-catalyzed asymmetric a-functionalization of carbonyl compoimds by electrophiles uncovered in the period 1971-2006 is provided by the Houk-List transition state and its analogs, which embody three important and... 

Figure 17.7 (a) Syn-face addition in Houk-List models (b) onti-face addition in Seebach-Eschenmoser transition state models. 

Figure 17.8 Computed Gibbs free energy profiles for the stereoselectivity-controlling C-C bond formation step in (a) enamine pathway involving a Houk-List transition...

Horeau principle 1286,1294 Horner-Wadsworth-Emmons (HWE) sequence 1309 host-guest complexes 687 Houk-List transition state model 475, 477, 478... 

Bahmanyar S, Houk KN (2001a) The origin of stereoselectivity in proline-catalyzed intramolecular aldol reactions. J Am Chem Soc 123 12911-12912 Bahmanyar S, Houk KN (2001b) Transition states of amine-catalyzed aldol reactions involving enamine intermediates theoretical studies of mechanism, reactivity, and stereoselectivity. J Am Chem Soc 123 11273-11283 Bahmanyar S, HoukKN, Martin HJ, ListB (2003) Quantum mechanical predictions of the stereoselectivities of proline-catalyzed asymmetric intermolec-ular aldol reactions. J Am Chem Soc 125 2475-2479 Barbas CF 3rd, Heine A, Zhong G, Hoffmann T, Gramatikova S, Bjoernstedt R, List B, Anderson J, Stura EA, Wilson I, Lemer RA (1997) Immune versus natural selection antibody aldolases with enzymic rates but broader scope. Science 278 2085-2092... 

Hoang L, Bahmanyar S, Houk KN, List B (2003) Kinetic and stereochemical evidence for the involvement of only one proline molecule in the transition states of proline-catalyzed intra- and intermolecular aldol reactions. J Am Chem Soc 125 16-17... 

Hoang, L., Bahmanyar, S., Houk, K. N., List, B. Kinetic and Stereochemical Evidence for the Involvement of Only One Proline Molecule in the Transition States of Proline-Catalyzed Intra- and Intermolecular Aldol Reactions. J. Am. Chem. Soc. 2003,125, 16-17. 

FIGURE 2.1. Working transition state models for the electrophilic attack to the enamine intermediate, (a) List-Houk model, (b) Steric model, (c) Seebach-Eschenmoser model. 

Agami s model was subsequently challenged by List, Lerner, and Barbas III in 2000 [8a], when they proposed a one-proline enamine mechanism for the proline-catalyzed intermolecular aldol reaction between ketones and aldehydes. Shortly afterwards, on the basis of DFT calculations, Houk and co-workers proposed a very similar mechanism for the Hajos-Parrish intramolecular aldol [19]. Using the B3LYP/6-31H-G(2df,p) level of DFT theory, Houk and co-workers [20] have seen that the energy difference between the two possible chair Zimmermann-Traxler-like transition states, which differ in the orientation of the enamine with... 

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). 

In 1971, Eder, Sauer, and Wiechert at Schering (72) and Hajos and Parrish at Hoffmann-La Roche 13,14) independently reported a proUne-catalyzed intramolecular aldol reaction of the triketone 16 as the key step in the synthesis of the diketone 17, a highly important intermediate in steroid synthesis. Remarkably, Hajos and Parrish obtained the diketone 18 in excellent yield and enantioselectivity with only 3 mol% of catalyst (Scheme 5). Acid-mediated dehydratiOTi then furnished the targeted 17. The accepted transition state for this reaction is believed to include one proline molecule as elucidated by List and Houk 21, 34). 

List [86] and Jorgensen [87] have recently independently described a novel application of L-proline (107) for catalysis of enantioselective hydrazidation of aldehydes [88]. For example, when aldehyde 106 is allowed to react with di-tert-butyl azodicarboxylate (95) in the presence of 10 mol% 107, adduct 108 is isolated in > 90% yield and 93% ee (Scheme 10.18) [87]. The product hydra-zides can be transformed into protected amino acid derivatives through a sequence that involves oxidation of the aldehyde to the corresponding carboxylic acid, esterification, deprotection, and N-N bond cleavage with Raney-Ni [86, 87]. The observed selectivity has been attributed to the intervention of transition state 111 [86]. This structure incorporates a hydrogen bond between proline s carboxyl group and the azodicarboxylate as a key organizing feature. The transition state structure has parallels to that proposed for the proline-cata-lyzed aldol addition reactions and is supported by quantum mechanical studies by Houk [89]. 

In the early 1970s, i-proline (222) was shown to function as a chiral catalyst for enantioselective aldol addition reactions (Chapter 4) [156]. With the aim of expanding the scope of proline-catalyzed asymmetric aldol additions [157], List reported that proline also catalyzes enantioselective Mannich reactions (Equation 19) [158]. Whereas most catalytic enantioselective Mannich reactions with aldehydes typically afford the corresponding syn products, Barbas, Tanaka, and Houk demonstrated that the complementary anti products such as 232 could be obtained highly selectively in the presence of the methyl-substituted proline catalyst 229 (99% ee, 98 2 dr. Scheme 11.33) [159]. It was proposed that these transformations proceeded through the energetically favored enamine 230 and transition state structure 231. 

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