DMAP analogs

A number of laboratories have targeted chiral DMAP analogs as acylation catalysts with perhaps the best success realized by Fu s planar chiral ferrocenyl... 

Vedejs (1996), Miller/Fu (1998) chiral phosphines, minimal peptides, chiral DMAP analogs Acyi-Anion Cataiysis... 

Scheme 4. Planar chiral DMAP analog 10 as a catalyst for kinetic resolution of secondary alcohols...

An interesting approach to translating remote chirality into enantiomer discrimination relies upon blocking one face of the heterocycle using axially chiral DMAP analogs. To this end, Spivey and co-workers have examined catalysts 39 and 40, obtained in optically pure form by preparative HPLC [38]. Catalyst 39 is effective for the kinetic resolution of aryl alkyl carbinols with good selec-tivities (krei=8.4-27, see Scheme 7). The substitution on the 4-position nitrogen... 

In the development of new chiral nucleophilic catalysts that were DMAP analogs, the chirality was introduced into the framework through the axial chirahty inherent in biaryl systems [70]. To this end, bromopyridine 197 was converted to biaryl 198 by cross-coupling with phenylboronic acids. 

In the late 1990s, several research groups worked on the development of chiral DMAP analogs. The works of Fu [23], Vedejs [24], and Fuji [25] led to the synthesis of powerful catalysts and the development of enantioselective organocatalytic reactions such as Steghch rearrangements, kinetic resolutions of secondary alcohols, kinetic resolution of amines, and so on (Scheme 1.8). 

Carbery et al. reported the novel design and rhodium-catalyzed synthesis of a heli-cenoidal DMAP analog bearing a 4-dialkylaminopyridine unit and a helical scaffold (Scheme 10.9) [11]. This compound could be employed successfully as a chiral Lewis base organocatalyst in the kinetic resolution of secondary alcohols with carboxylic acid anhydrides (Scheme 10.10) [11]. 

Compound (S)-4, devised by Johanssen and coworkers as a new type of ferrocene-based planar chiral ferrocene-based DMAP analog and obtained in six steps from enantiopure Kagan s ferrocene sulfoxide, gave only marginal enantioselectivities in the Steglich rearrangement of an O-carbonylated oxazolone (Scheme 40.8) [16]. 

Figure 40.2 Vedejs second-generation chiral DMAP analogs AcOLeDMAP (8) and BnOLeDMAP (9).

Ga—E monomers. The central structural parameters of Ga-containing monomers dmap—Ga(R2)E(Tms)2 (E = P 65, As 66, Sb 67), which are summarized in Table 16, are comparable to those of analogously substituted Al—E monomers. 

Reaction of N,N-dimethylaniline with 1-cyanobenziodoxol 1783 to afford N-methyl-N-cyanomethylaniline 1784 in 97% yield has been discussed in Section 12.1 [31]. Analogously, oxidation of dimethylaniline with iodosobenzene and trimethylsilyl azide 19 at 0°C in CDCI3 gives the azido compound 2040 in 95% yield, iodobenzene, and HMDSO 7 [194, 195] (Scheme 12.56). Likewise, the nucleophilic catalyst 4-dimethylaminopyridine (DMAP) is oxidized, in 95% yield, to the azide 2041, which is too sensitive toward hydrolysis to 4-N-methylaminopyri-dine to enable isolation [194, 195]. Amides such as 2042, in combination with tri-... 

Dimethylamino)pyridine (1, DMAP) and its analogs, particularly 4-(pyrrolidino)pyridine (2, PPY) have acquired enormous importance and utility as supemucleophilic catalysts in synthetic organic and polymer chemistry (1, 2). 

The tremendous scope of utilization of DMAP and PPY as catalysts has led to an active interest in the development of their polymeric analogs. The pioneering work was carried out by Hierl et al (8) and Delaney et al. (9). They attached 4-dialkyl-aminopyridine derivatives to poly(ethyleneimine) and found the modified polymers to be highly active catalysts for hydrolysis of p-nitrophenylcarboxylates. Since then, many research groups have reported the synthesis of polymers functionalized with 4-dialkyl-aminopyridine (10-18). 

Analogous rearrangements have also been performed by both Fu [73] and Vedejs [105] on (9-acyl benzofuranones and (9-acyl oxindoles to provide synthetic intermediates potentially suitable for elaboration to diazonamide A and various oxin-dole-based alkaloids such as gelsemine respectively. Peris has also examined both Fu s and Vedejs chiral 4-DMAP catalysts for effecting diastereoselective carboxyl migrations of 3-arylbenzofuranones [109]. 

Spivey and coworkers reported in 1999 the nse of axially chiral analogs of 4-DMAP 32 and 33, which rely on the high barrier of rotation about an aryl-aryl bond at the 3-position of 4-DMAP to produce atropisomers that are selective in the acylation of. yec-alcohols (Scheme 13) [117-127],... 

Scheme 13 Spivey s axially-chiral analog of 4-DMAP in the KR of an alkyl aryl carbinol. [117-127]...

Examples of nonasymmetric organocatalysts that were introduced in the 1950s include analogs of thiamine reported by Breslow in 1957 as an alternative to cyanide as a catalyst for the benzoin condensation [8]. Asymmetric versions of these thiazolium catalysts were used in organocatalytic benzoin condensations by Sheehan and Hunneman in 1966 [9]. In another important development, in 1969 the nucleophilic catalyst 4-(dimethylamino)pyridine (DMAP), which is now widely used for difficult esterifications, was reported by Steglich [10]. 

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