Nitroaldol transition state

Scheme 6.167 Proposed transition-state models for the enantioselective Henry (nitroaldol) reaction in the presence of (S,S)-configured catalyst 183 TS 1 anti, anti conformation TS 2 gauche-onfi conformation TS 3 gauche-onfi conformation.

Scheme 6.170 Suggested transitions states for the anti-diastereoselective Henry (nitroaldol) reaction promoted by (R,R)-catalyst 186 (TS 1) and its (S,S)-isomer 183 (TS 2) to demonstrate the match/mismatch relationship between guanidine-thiourea catalyst and (S)-a-aldehyde.

Figure 9.1 Plausible transition-state model for nitroaldol reactions...

Figure 21. Proposed transition states of diastereoselective and enantioselective nitroaldol reactions.

It seems that the syn selectivity in the nitroaldol reaction can best be explained as arising from steric hindrance in the bicyclic transition state it seems that the greater stereoselectivity obtained by use of catalysts 27 and 28 can be ascribed to increased catalyst stability, even in the presence of an excess of highly acidic nitroalkanes. The syn-selective asymmetric nitroaldol reaction was successfully applied to the catalytic asymmetric synthesis of t/zreo-dihydrosphingosine 45, which elicits a variety of cellular responses by inhibiting protein kinase C. An efficient synthesis of erythro-AHPA 42 from L-phenylalanine was, moreover, achieved by using LLB (Sch. 9) [59],... 

The proposed mechanism for the asymmetric nitroaldol reaction catalyzed by heterobimetallic lanthanoid complexes is shown in Scheme 2 [9]. In the initial step, the nitroalkane component is deprotonated and the resulting lithium nitr-onate coordinates to the lanthanoid complex under formation of the intermediate I [ 10]. Subsequent addition of the aldehyde by coordination of the C=0 double bond to the lanthanoid(III) ionic center leads to intermediate II, in which the carbonyl function should be attacked by the nitronate via a six-membered transition state (in an asymmetric environment). A proton exchange reaction step will then generate the desired optically active nitroalkanol adduct with regeneration of the free rare earth complex LnLB. 

Catalytic enantio- and diastereoselective nitroaldol reactions were explored by using designed guanidine-thiourea brfunctional organocatalysts like 15 (Figure 4.4) under mUd and operationally simple biphasic conditions. These catalytic asymmetric reactions have a broad substrate generality with respect to the variety of aldehydes and nitroalkanes [43]. On the basis of studies of structure and catalytic activity relationships, a plausible guanidine-thiourea cooperative mechanism and a transition state of the catalytic reactions are proposed. 

The nitroaldol (Henry) reaction provides 1,2-nitro alkanols under atom-economical proton transfer conditions, which allows for easy access to highly versatile 1,2-amino alcohols (Scheme 6) [31]. A number of catalytic systems have been devised to render this useful C-C bond-forming reaction asymmetric however, diastereoselectivity remained a longstanding problem, in particular for a ri-selective reactions [14, 32, 33]. syw-Selective reaction can be achieved by a monometalhc catalytic system as shown in Fig. 9a, where both an aldehyde and a nitronate coordinate to the metal center to give syn product due to steric repulsion [34—36]. To make the reaction proceed in fluft-selective manner, different strategy in catalyst design is required [37, 38]. Simultaneous activation of both the aldehyde and the nitronate in an anti-paraUel fashion can afford the anti-1,2-nitro alkanols preferentially (Fig. 9b). To attain the a ri-paraUel transition state, a heterobimetalhc catalyst offers a suitable... 

The use of chiral P-spiro salts 5-8 in a nitroaldol reaction was recently reported by the Ooi group (Table 29.1) [10]. The reaction proceeded in the presence of 5 mol% of the chiral tetraaminophosphonium salt and KO Bu (5 mol%). It was postulated that the nitroalkane would be deprotonated by triaminoiminophospho-rane I, which would be the actual catalyst generated in situ from 5-8 and a strong base, forming a chiral phosphonium nitronate complex. An acyclic transition state model II predicting the formation of the anti adduct was proposed in which the Si-face of the nitronate would be set up to approach the Re-face of the aldehyde without significant sterical hindrance (Scheme 29.5). 

Feng and Hu reported a successful nitroaldol reaction of a-ketophosphonates by using a combination of bis-chiral secondary amide 22 and 2,4-dinitrophenol (23) (Scheme 29.9) [23], In the proposed transition state, one of the piperidine moieties is pro to na ted by the acidic additive, which activates the a-ketophosphonate via hydrogen bonding, and the other piperidine deprotonates nitromethane. With this catalyst system, numerous different nitroaldol compounds may be obtained with high optical purities. A Bu OMe/PhOMe (2 1) solvent mixture seems critical... 

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