Dynamic kinetic asymmetric synthesis

Nicholson, L.W., Rand, C.A., and Burk, M.J. (2004) Chemoenzymatic approaches to the dynamic kinetic asymmetric synthesis of aromatic amino acids. Tetrahedron Asymmetry, 15, 2793-2796. 

The Gabriel synthesis represents another indirect but highly valuable approach to amines. Trost has demonstrated a method for the asymmetric ring-opening of butadiene monoepoxide by use of one equivalent of phthalimide, 7t-allylpalladium chloride dimer, and the chiral bisphosphine 22 (Scheme 7.37). The dynamic kinetic asymmetric transformation proceeded through a putative achiral intermedi-... 

A classical approach to driving the unfavorable equilibrium of an enzymatic process is to couple it to another, irreversible enzymatic process. Griengl and coworkers have applied this concept to asymmetric synthesis of 1,2-amino alcohols with a threonine aldolase [24] (Figure 6.7). While the equilibrium in threonine aldolase reactions typically does not favor the synthetic direction, and the bond formation leads to nearly equal amounts of two diastereomers, coupling the aldolase reaction with a selective tyrosine decarboxylase leads to irreversible formation of aryl amino alcohols in reasonable enantiomeric excess via a dynamic kinetic asymmetric transformation. A one-pot, two-enzyme asymmetric synthesis of amino alcohols, including noradrenaline and octopamine, from readily available starting materials was developed [25]. 

Steinreiber, J., Schurmann, M., van Assema, F. et al. (2007) Synthesis of aromatic 1,2-amino alcohols utilizing a bienzymatic dynamic kinetic asymmetric transformation. Advanced Synthesis and Catalysis, 349, 1379-1386. 

Trost, B.M. and Andersen, N.G., Utilization of molybdenum- and palladium-catalysed dynamic kinetic asymmetric transformations for the preparation of tertiary and quaternary stereogenic centers a concise synthesis of tipranavir, J. Am. Chem. Soc., 2002, 124, 14320-14321. 

A DYKAT (dynamic kinetic asymmetric transformation) approach has been taken to de novo synthesis of triketide- and deoxy-sugars from racemic /i-hydroxyal-dehydes.119 Using proline as catalyst, the process involves continuous amino acid-mediated racemization of the acceptor /3-hydroxyaldehydc in combination with direct... 

Zirconaaziridines, which can be prepared in a few steps from commercially available starting materials, have polar Zr-C bonds that permit the insertion of many electrophilic reagents (C=0, C=N) as well as alkynes (C=C) and alkenes (C=C). Appropriate substituents on their ring carbons make zirconaaziridines chiral and raise the possibility of their use in asymmetric synthesis. The lability of their chiral centers distinguishes zirconaaziridines from other organo-metallic reagents and makes it possible for them to undergo dynamic kinetic asymmetric transformations . 

A dynamic kinetic asymmetric transformation (DYKAT) of racemic vinyl aziridine 347 yielded the enantiopure imidazolidinone 348 (Scheme 90) <20050L823>. This transformation was the initial step in a total synthesis of (+)-pseudodistomin D. 

Later work has shown that a dynamic kinetic asymmetric transformation could be obtained if the acetates were converted into carbonate groups. With the tetra(2,2,2-trichloroethyl) carbonate derivative, reactions with carbon and nitrogen nucleophiles gave exclusively the monosubstituted products in high yield (61-95%) and excellent enantiomeric excesses (95-99%). However, car-boxylate nucleophiles afforded the disubstituted products in high yield and enantiomeric excess (eq 7). This allowed an efficient synthesis of D-myo-inositol-l,4,5-trisphosphate to be devised. 

This methodology has been expanded to geranyl methyl carbonate for the synthesis of the vitamin E nucleus, and to tiglyl methyl carbonate for the synthesis of (—)-calanolide A and B. In the latter example, the anthracenyldiamine -based ligand was required for optimum selectivity. The synthesis of (—)-aflatoxin B lactone utilizes a dynamic kinetic asymmetric transformation, whereby a suitably functionalized phenol reacts with a racemic 5-acyloxy-2-(5//)-furanone to provide a single product in 89% yield. One final example of phenol as a nucleophile is for the deracemization of Baylis-Hillman adducts." ... 

Notable were highly enantioselective additions of N-phosphonyl imines with dialkyl zinc or hydroxyketones and a one-pot reaction of alkynylzirconocenes with alkynyl phosphazenes and zinc carbenoids to give single isomer cyclopropylphosphonamides. The importance of enantioselective and dynamic kinetic asymmetric transformations is illustrated in many publications. Other interesting reports cover the use of phosphoramidates for the synthesis of allylic amines as well as the first example of C-P cleavage of a-aminophosphono acids using periodate. 

The current review is of necessity selective. Over the two year period covered, there has been impressive advances in several areas of P(V) chemistry. For example, biological aspects of quinquevalent phosphorus acids chemistry continue to increase in importance. A wide variety of natural and unnatural phosphates including inositols, lipids, some carbohydrates and their phospho-nates, phosphinates and fluorinated analogues has been synthesized. Special attention has been paid to the synthesis of phosphorus analogues of all types of amino acids and some peptides. Numerous investigations of phosphate ester hydrolysis and related reactions continue to be reported. Interest in approaches to easier detoxification of insecticides continues. A number of new and improved stereoselective synthetic procedures have been elaborated. The importance of enantioselective and dynamic kinetic asymmetric transformations is illustrated in many publications. 

Trost s dynamic kinetic asymmetric amine aiiyiation appiied to the synthesis of 3,5-dideoxy-2,5-imino-D-manni-toi and (-)-buigecinine... 

One good example of the application of this technology is in the AAA reaction of a racemic vinyl epoxide. The epoxide undergoes a dynamic kinetic asymmetric transformation (DYKAT) by reaction with p-methoxybenzyl alcohol, the standard ligand, and a palladium source. The product is obtained in 69% yield and 98% e.e. After further manipulations a key building block for the nonpeptidic protease inhibitor tipranavir was produced. Coupling of this intermediate with a synthon obtained using a molybdenum-catalyzed DYKAT process led to an advanced intermediate in a total synthesis of tipranavir (Scheme 20.14). ... 

Cycloaddition of cyclopropanes to aldehydes leads to the formation of tetrahydrofurans derivatives, whose enantiomeric form can be obtained either by using enantioenriched cyclopropane substrates or by a dynamic kinetic asymmetric transformation. In this regard, Johnson et al. reported a dynamic kinetic asymmetric [3 -I- 2] cycloaddition of racemic cyclopropanes 63 for the enantioselective synthesis of tetrahydrofurans 64. In this study, the magnesium catalyst can promote the ring opening of the racemic cyclopropane and catalyses the reaction of one of the ring-opened enantiomers with the aldehydes (Scheme 3.19). 

The stereogenic centers were then introduced by palladium-catalyzed dynamic kinetic asymmetric transformatitHi. ITierefore, 41 was coupled with lactone 42 in the presence of chiral ligand (RJt)-43 and gave 44 in 89% yield. The synthesis of 42 is shown below in Scheme 2.6. Compound 44 was subjected to an intramolecular Heck reaction followed by acidic cleavage of the ester function 45). The intramolecular Heck reaction only produced one diastereomer, because the c/s-annelated rings are favored. Scandium(lll)-mediated cyclizatitMi and reduction of the lactone with DIB ALII yielded (-)-aflatoxin Baa (46). It was acetoxylated and then pyiolyzed to give (-)-aflatoxin Bi (1) in 1.6% overall yield and nine linear steps from catechol (40). 

Trost BM, Toste FD (1999) Palladium-Catalyzed Kinetic and Dynamic Kinetic Asymmetric Transformation of 5-Acyloxy-2-(5H)-furanone. Enantioselective Synthesis of (-)-Aflatoxin B Lactone. J Am Chem Soc 121 3543... 

The importance of conduritol B and its derivatives as synthetic building blocks is amply demonstrated by its extensive use in natural product synthesis as presented previously. Trost et al. ° reported dynamic kinetic asymmetric transformations of... 

In 2007, Griengl et al. developed the synthesis of chiral aromatic 1,2-amino alcohols on the basis of a bienzymatic dynamic kinetic asymmetric transformation process.The reaction occurred between a benzaldehyde derivative and glycine in the presence of L-threonine aldolase from Pseudomonas putida and L-tyrosine decarbmylase from either Enterococcus faecalis or two genes from Enterococcus faecium. The best results were obtained for the production of (5 )-octopamine (99%, ee = 81%), and (5 )-noradrenaline (76%, ee = 79%), as shown in Scheme 4.16. 

Recently, Lin et al. demonstrated that the propargyl alcohol could participate in such a transformation for the synthesis of chiral dihydrofurans [53]. The reaction began with a challenging oxa-Michael addition to cinnamaldehyde derivatives, which was followed by a secondary amine/Pd complex-catalyzed nucleophilic addition/ isomerization of the alkyne moiety in excellent yields and enantioseleclivities (Scheme 9.58). Since the oxa-Michael addition of propargyl alcohol to 0[,P-unsaturated aldehydes was a slow process, this cascade reaction proceeded through a dynamic kinetic asymmetric transformation (DYKAT) process, whereby it made the overall reaction proceed efficiently and with high stereocontrol using the second reaction with precise stereocontrol to shift the first reversible oxa-Michael addition selectively. 

Martin-Matute, B. and Backvall, J.-E. (2004). Ruthenium- and enzymedynamic kinetic asymmetric transformation of 1,4-diols Synthesis of gamma-hydroxy ketones. /. Org. Chem., 69,9191-9195. 

Millet, R., Traff, A. M., Petrus, M. L., and Backvall, J. E. (2010). Enantioselective synthesis of syn- and anti-l,3-aminoalcohols via beta-aminoketones and subsequent reduction/ dynamic kinetic asymmetric transformation. /. Am. Chem. Soc., 132,15182-15184. 

In 2009, Parsons and Johnson reported the synthesis of enantio-enriched tetrahydrofurans via a dynamic kinetic asymmetric cycloaddition of racemic cyclopropanes with aldehydes under the influence of a chiral Lewis acid as illustrated in Scheme 10.40 and Table 10.13 [38]. 

Trost and Jiang recently reported on an asymmetric allylic alkylation for the synthesis of the quaternary center of the cyclopentyl core of viridenomycin 158 (Scheme 13.42). Palladium-catalyzed dynamic kinetic asymmetric transformation of racemic isoprene monoepoxide with ketoester 155 furnishes lactol 156 in 71% yield as a mixture of diastereo-mers. The alkylation was performed with chiral ligand 148... 

Leijondahl K, Boren L, Braun R, Backvall J-E. Enzyme- and ruthenium-catalyzed dynamic kinetic asymmetric transformation of 1,5-diols. Application to the synthesis of (+)-solenop-sin A. J. Org. Chem. 2009 74 1988 1993. 

The novel phenomenon of converting racemic substrates into a single enantiomer of the product hy dynamic kinetic resolution (DKR) via racemization of the substrates has been a formidable challenge in asymmetric synthesis. Recently, DKR has been receiving increasing attention since it can overcome the limitations... 

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