Aldol reactions asymmetric reactions

Scheme 3.20. Proposed mechanism of asymmetric nitro-aldol reactions catalyzed by LLB, LLB-II, or LLB-LI nitronate...

Kee TP, Nixon TD (2003) The Asymmetric Phospho-Aldol Reaction. Past, Present, and Future. 223 45-65... 

The Asymmetric Phospho-Aldol Reaction. Past, Present, and Future... 

Asymmetric Mukaiyama aldol reactions have also been performed in the presence of Lewis-acid lanthanoid complexes combined with a chiral sulfonamide ligand. Similar enantioselectivities of about 40% ee were obtained for all... 

Organic-Base Catalyzed. Asymmetric direct aldol reactions have received considerable attention recently (Eq. 8.98).251 Direct asymmetric catalytic aldol reactions have been successfully performed using aldehydes and unmodified ketones together with chiral cyclic secondary amines as catalysts.252 L-proline and 5,5-dimethylthiazolidinium-4-carboxylate (DMTC) were found to be the most powerful amino acid catalysts for the reaction of both acyclic and cyclic ketones as aldol donors with aromatic and aliphatic aldehydes to afford the corresponding... 

In 2000, Morken et al. reported the first examples of catalytic asymmetric reductive aldol reactions [21]. Using Rh(BINAP) (5mol%) as catalyst and Et2MeSiH as reductant, the syn-selective (1.7 1) coupling of benzalde-hyde and methyl acrylate produced the diastereomers 35-syn and 35-anti in 91% ee and 88% ee, respectively. Using phenyl acrylate as the nucleophilic partner, a favorable yield of 72% was obtained for the aldol product 36 (Scheme 12). Several aldehydes were examined, which exhibit higher levels of syn-selectivity. Expanding the scope of substrates and acrylates under... 

Kawai K, Majima T (2004) Hole Transfer in DNA by Monitoring the Transient Absorption of Radical Cations of Organic Molecules Conjugated to DNA. 236 117-137 Kee TP, Nixon TD (2003) The Asymmetric Phospho-Aldol Reaction. Past, Present, and Future. 223 45-65... 

Over the last few years several examples have been reported in the field of asymmetric catalysis that are based on the interaction of two centers.6,119 Recently, Shibasaki and coworkers have developed an asymmetric two-center catalyst. Scheme 3.14 shows preparation of optically active La binaphthol (BINOL). This catalyst is effective in inducing the asymmetric nitro-aldol reaction, as shown in Scheme 3.15. 

Scheme 3.15. La-BINOL complex-catalyzed asymmetric nitro-aldol reactions...

A yyw-selective asymmetric nitro-aldol reaction has been reported for structurally simple aldehydes using a new catalyst generated from 6,6-bis[(triethylsilyl)ethynyl]BINOL (g in Scheme 3.18).126 The syn selectivity in the nitro-aldol reaction can be explained by steric hindrance in the bicyclic transition state as can be seen in Newman projection. In the favored transition state, the catalyst acts as a Lewis acid and as a Lewis base at different sites. In contrast, the nonchelation-controlled transition state affords anti product with lower ee. This stereoselective nitro-aldol reaction has been applied to simple synthesis of t/ircodihydrosphingosine by the reduction of the nitro-aldol product with H2 and Pd-C (Eq. 3.79). 

Figure 14.12 Asymmetric tandem aldol reaction using 2-deoxyribose-5-phosphate aldolase (DERA) and its application for production of Atorvastatin...

Pro-chiral pyridine A-oxides have also been used as substrates in asymmetric processes. Jprgensen and co-workers explored the catalytic asymmetric Mukaiyama aldol reaction between ketene silyl acetals 61 and pyridine A-oxide carboxaldehydes 62 <06CEJ3472>. The process is catalyzed by a copper(II)-bis(oxazoline) complex 63 which gave good yields and diastereoselectivities with up to 99% enantiomeric excess. 

Scheme 72 Asymmetric nitroso aldol reactions of achiral enamines...

Studies of catalytic asymmetric Mukaiyama aldol reactions were initiated in the early 1990s. Until recently, however, there have been few reports of direct catalytic asymmetric aldol reactions [1]. Several groups have reported metallic and non-metallic catalysts for direct aldol reactions. In general, a metallic catalysis involves a synergistic function of the Bronsted basic and the Lewis acidic moieties in the catalyst (Scheme 2). The Bronsted basic moiety abstracts an a-pro-ton of the ketone to generate an enolate (6), and the Lewis acidic moiety activates the aldehyde (3). 

The asymmetric catalytic aldol reaction of a silyl enol ether can be performed in a double and two-directional fashion to give the 1 2 adduct in the silyl enol ether form with >99% ee and 99% de in 77% isolated yield (Scheme 8C.25) [59]. The present catalytic asymmetric aldol reaction is characterized by a kinetic amplification phenomenon of the product chirality, going from the one-directional aldol intermediate to the two-directional product (Figure 8C.8). Further transformation of the pseudo C2 symmetric product, while still being protected as the silyl enol ether, leads to a potent analog of an HIV protease inhibitor. 

Keck [63] and Carreira [64] have independently reported catalytic asymmetric Mukaiyama aldol reactions. Keck et al. also reported the aldol reaction of an a-benzyloxy aldehyde with a Danishefsky s diene. The aldol product was transformed to the corresponding HDA-type product through acid-catalyzed cyclization. In these reactions, the catalyst that is claimed to... 

Asymmetric Mukaiyama aldol reactions in aqueous media [EtOH-H20 (9 1)] were reported with FeCl2 and PYBOX ligands 27a [36] and 27b [37]. The latter provides product 28 with higher yield and diastereo- and enantioselectivity (Scheme 8.9). The ee values given are for the syn-diastereoisomer. Whereas ligand 27a is a derivative ofL-serine, compound 27b has four stereogenic centers, since it was prepared from... 

Scheme 8.9 Asymmetric Mukaiyama aldol reactions with Fe(ll)-PYBOX catalysts.

Scheme 3.11 Asymmetric diazo-aldol reaction and one-pot synthesis.

Table 9.2 Asymmetric Mukaiyama aldol reactions catalyzed by chiral quaternary ammonium fluorides4b with various methods of preparation.

Recently, a conceptually different synthesis of MeBmt using an asymmetric glycine aldol reaction was reported by Evans and Weber [29]. The key step consists in the stereochemically controlled condensation of the chiral glycine enolate synthon (23) with the (R)-aldehyde (24) mediated by stannous triflate (tin salt of trifluoromethanesulphonic acid). The desired syn-aldol adduct (25) was isolated in form of the heterocyclic compound (26). The sense of asymmetric induction in the aldol reaction was established by conversion of (26) over three steps into uniform MeBmt (3). 

The concept In the first example of an organic base-catalyzed asymmetric intermolecular aldol reaction, Denmark et al. impressively demonstrated that the pres-... 

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