DMAP chiral derivatives

Ruble JC, Tweddell J, Fu GC (1998) Kinetic resolution of arylalkylcarbinols catalyzed by a planar-chiral derivative of DMAP a new benchmark for nonenzymatic acylation. J Org Chem 63 2794-2795... 

Bappert E, Mueller P, Fu GC (2006) Asymmetric [3 -i- 2] annulations catalyzed by a planar-chiral derivative of DMAP. Chem Commun 2604—2606... 

In addition to the planar chiral ferrocenyl catalysts 15-18, 24 developed by Fu, a number of other chiral derivatives of 4-DMAP and 4-PPY [4, 47, 48] have been explored by other groups as organocatalysts for KR of ec-alcohols. Contributions have been made by the groups of Vedejs [104, 105, 110, 111], Fuji and Kawabata... 

Initially reported for the resolution of racemic alcohols, Fu s planar-chiral derivatives of 4-dimethylaminopyridine (DMAP) 45-46 have been also successfully exploited as catalyst in diverse asymmetric transformations [20], including enantioselective protonation of ketenes [21]. These planar-chiral ferrocenes 45-46 are... 

Enantioenriched alcohols and amines are valuable building blocks for the synthesis of bioactive compounds. While some of them are available from nature s chiral pool , the large majority is accessible only by asymmetric synthesis or resolution of a racemic mixture. Similarly to DMAP, 64b is readily acylated by acetic anhydride to form a positively charged planar chiral acylpyridinium species [64b-Ac] (Fig. 43). The latter preferentially reacts with one enantiomer of a racemic alcohol by acyl-transfer thereby regenerating the free catalyst. For this type of reaction, the CsPhs-derivatives 64b/d have been found superior. 

Tao B, Ruble JC, Hole DA, Fu GC (1999) Nonenzymatic kinetic resolution of propargylic alcohols by a planar-chiral DMAP Derivative crystallographic characterization of the acylated catalyst. J Am Chem Soc 121 5091-5092... 

Carbon dioxide is one of the most abundant carbon resources on earth. It reacts with an epoxide to give either a cyclic carbonate or a polycarbonate depending on the substrates and reaction conditions. Kinetic resolution of racemic propylene oxide is reported in the formation of both cyclic carbonate and polycarbonate. The fe ei value defined as ln[l-(conversion)(l+%ee)]/ln[l-(conversion)(l% ee)] reached 6.4 or 5.6 by using a Co(OTs)-salen complex with tetrabutylammonium chloride under neat propylene oxide or using a combination of a Co-salen complex and a chiral DMAP derivative in dichloromethane, respectively. 

Interestingly, this catalyst and related systems typically function as chiral DMAP-type catalysts.However, in this case, mechanistic studies suggest that the role of 36 is to serve as a conjugate base for the protic catalyst derivative. 

Hence, the group developed a series of planar chiral ferrocenyl 4-DMAP and 4-(pyrrolidino)pyridine (4-PPY) derivatives (15-18) that have proved to be highly versatile and efficient catalysts for many acyl transfer processes (Fig. 5) [25, 26, 66-82, 93, 99, 103, 105]. 

Fu s planar chiral ferrocenyl 4-DMAP derivative 16 is also the first organocatalyst that has been reported to efficiently perform the KR of certain propargylic ec-alcohols [83]. These KRs were achieved using 1 mol% of catalyst 16 and Acp as the acylating agent in tert-smyl alcohol at 0 °C in the absence of a stoichiometric auxiliary base... 

An early synthesis of A5-palmitoy]-.S -[2,3-bis(palmitoyloxy)propyl]cysteine employed cysteine methyl ester, however, this leads to difficulties in the saponification step of the tri-palmitoylated residue. 96 The optimized procedure, in which the cystine di-fert-butyl ester is used, 90 is outlined in Scheme 6 after N-acylation with palmitoyl chloride, the ester is reduced to the cysteine derivative for S-alkylation with l-bromopropane-2,3-diol to yield chirally defined isomers if optically pure bromo derivatives are used. Esterification of the hydroxy groups is best carried out with a 1.25-fold excess of palmitic acid, DCC, and DMAP. The use of a larger excess of palmitoyl chloride is not recommended due to purification problems. The diastereomeric mixture can be separated by silica gel chromatography using CH2Cl2/EtOAc (20 1) as eluent and the configuration was assigned by comparison with an optically pure sample obtained with 2R)- -bromopropane-2,3-diol. 

Introducing the Tau residue into a peptide according to the first approach demands protection of the amino group, usually in the form of a Z-derivative and turning the sulfonic acid into sulfonyl chloride. Synthesis of (j-su Ifonamidopeptides via an iterative process, both in solution and in the solid phase, has been described.11201 Chiral methylene sulfinamide peptides can be synthesized both in solution and in the solid phase using the sulfonyl chlorides derived from enantiomerically pure 2-substituted taurines under mild coupling conditions (DMAP catalysis and excess methyl trimethylsilyl dimethylketene acetal as a proton trap).11261... 

The preparation of optically active /Mactams by asymmetric synthesis is also a topic of major interest, because of the pharmaceutical and biochemical importance of those molecules [44]. A typical and economical route consists of a [2+2]-cycloaddition of a ketene to an imine. Many diastereoselective versions of this reaction type are known [45] as well as catalytic processes involving chiral (metal) catalysts [46, 47] or biocatalysts [48]. A [2+2]-cycloaddition of a ketene to an imine, however, can also be performed very efficiently when applying nucleophilic amines as chiral catalysts [49-60]. Planar-chiral DMAP derivatives have also been found to be suitable catalysts [61]. 

The Vedejs group also reported the centrally chiral DMAP derivatives 8 and 9... 

Later studies focused on the planar chiral DMAP derivative 21c as catalyst and use of acetic anhydride as an inexpensive and readily available acyl donor [19]. Under these conditions (2 mol% catalyst loading, r.t.) kinetic resolution of several racemic alcohols could be achieved with selectivity factors up to 52 (Scheme 12.7). As a consequence, enantiomerically highly enriched alcohols (> 95% ee) could be obtained at conversions only slightly above 50%. 

The axially chiral DMAP derivatives 22a-d were developed by Spivey et al. [23-25], In these catalysts the chiral axis is positioned meta to the pyridyl nitrogen... 

Jeong, Kim et al. reported use of the chiral DMAP derivative 22e, which was synthesized from 3-amino-DMAP, Kemp s triacid, and N-acetyl-2,2 -diamino-l,l -binaphthyl [26], As summarized in Scheme 12.11, selectivity factors up to 21 were observed with 1 mol% modular catalyst 22e in the kinetic resolution of a variety of secondary alcohols with acetic anhydride in tert-amyl alcohol as solvent, conditions first described by Fu et al. [20]. 

Fu et al. used the planar chiral DMAP derivative 46 (Scheme 13.24) [39]. Although this catalyst has been employed successfully for kinetic resolution of a large variety of racemic secondary alcohols (Section 12.1), substrate 47 seems to be the only meso-diol that has been desymmetrized by use of the acylation catalyst... 

Selectivity in enantiotopos-differentiating acylation and phosphorylation of meso-diols can rival that of enzymes. The organocatalysts employed include chiral phosphines, chiral diamines, chiral DMAP derivatives and peptides identified from combinatorial libraries. The highest selectivity in meso diol desymmetrization has been achieved with a planar-chiral Fu catalyst. It seems the substrate scope of this process is not yet broadly explored. Because of their sequential variability it is to be... 

The planar chiral DMAP derivative 79a proved successful also in the dynamic kinetic resolution of racemic azlactones by ring-opening with alcohols (Scheme... 

Construction of quaternary stereocenters by enantiocontrolled oxygen to carbon acyl shift is not limited to the azlactone structure. Using the pentaphenylated planar chiral DMAP derivative 79c (Scheme 13.42) Fu and Hills achieved rearrangement of O-acylated oxindoles 84 (Scheme 13.45) and benzofuranones 85 (Scheme 13.46) with very good yields and enantiomeric excesses up to 99% [88]. 

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