Chiral -■ symmetrical aminal

Chiral amines and diamines are readily available substrates for the synthesis of ligands for transition metal-catalysed reactions since they can easily be transformed into chiral ureas and thioureas. Therefore, several groups have prepared chiral symmetrical ureas and thioureas, dissymmetrical ureas and thioureas, amino-urea and thiourea derivatives. Finally polyureas and non-soluble polythioureas were also prepared and tested as ligands for asymmetric catalysis. 

J. Aube, Chemtracts Org. Chem. 2, 46-49 (1989) New C2-Symmetrical Chiral Secondary Amines". 

Being inspired by Maruoka s results with the C2-symmetric binaphthyl-derived quaternary ammonium salt [21], Lygo and colleagues designed a quaternary ammonium salt 23, comprising conformationally flexible biphenyl units and commercially available chiral secondary amines [22], A library of 40 quaternary ammonium salt was synthesized and evaluated for their catalytic efficiency in the asymmetric alkylation of... 

The use of an enamine derived from a chiral C2-symmetric amine such as (2R, 5R)-2,5-dimethylpyrrolidine leads to products 30 with high diastereoselectivity as well as high stereofacial selectivity (equation 7)32. In this case the radical addition is thought to take place from the relatively less hindered face of the enamine 29. 

Planar chiral compounds should also be accessible from the chiral pool. An example (with limited stereoselectivity) of such an approach is the formation of a ferrocene derivative from a -pinene-derived cyclopentadiene (see Sect. 4.3.1.3 [81]). A Cj-symmetric binuclear compound (although not strictly from the chiral pool, but obtained by resolution) has also been mentioned [86]. Another possibility should be to use the central chiral tertiary amines derived from menthone or pinene (see Sect. 4.3.1.3 [75, 76]) as starting materials for the lithiation reaction. In these compounds, the methyl group at the chiral carbon of iV,iV-dimethyl-l-ferrocenyl-ethylamine is replaced by bulky terpene moieties, e.g., the menthane system (Fig. 4-2 le). It was expected that the increase in steric bulk would also increase the enantioselectivity over the 96 4 ratio, as indicated by the results with the isopropyl substituent [118]. However, the opposite was observed almost all selectivity was lost, and lithiation also occurred in the position 3 and in the other ring [134]. Obviously, there exists a limit in bulkiness, where blocking of the 2-position prevents the chelate stabilization of the lithium by the lone pair of the nitrogen. 

SCHEME 22. Synthesis of C4-symmetric resorcarenes via Mannich condensation with a chiral primary amine as an auxiliary... 

Most asymmetric Diels-Alder reactions have the chiral auxiliary attached to the dienophile as an ester or an amide. There is no such obvious place to attach an auxiliary to a diene but the chiral analogue 161 of Danishefsky s diene has a C2 symmetric amine 164 attached as an enamine. Cycloaddition without a Lewis acid gives good selectivity in the formation of adduct21 162. Reduction and hydrolysis releases the enone 163 in reasonable ee. 

Pyrrolidinyl amides undoubtedly form Z((9)-enolates, and the [2,3]-Wittig rearrangement of the -alkene (entry 5, [69] is highly selective. The Z-alkene was not tested, and propargylic amide enolates do not rearrange [70]. Entry 5 also shows the highest yield in the Table. As will be seen, amides of C2-symmetric amines can be excellent chiral auxiliaries in this process. 

Following the same approach, a C 2-symmetric amine, (K, W)-bis(2-methoxy-1-phenyl ethyOamme (28) was obtained from (7 )-phenylglycine23. Both amino alcohols have been used as chiral bases for enantioselective deprotonation and elimination reactions (Section C.). 

R = nPr, iPr, cyclohexyl, cyclopentyl, fBu, Ph-C=C) to form heterocyclic enamines 27 which, after acid-catalyzed removal of the chiral C2-symmetrical amine, yielded the hexa-hydropyridazines 28 (six examples) with an ee of 90-91 %. The successful use of another chiral amine, [(5,5 )-3,5-dimethylmorpholine], gives further indication of the efficiency of asymmetric induction by means of coupling at the C-2 position of the diene. 

Whitesell observed that alkylation at the a-carbon of an amide of a C2-symmetric amine, in which the amine acts as a chiral auxiliary, should result in effective symmetric induction [166]. The C2-symmetric aziridines 519 and 520 are readily accessible from 503 and 514, respectively. Ring opening of either epoxide with sodium azide, mesyl activation of the free hy oxy group, and lithium aluminum hydride reduction of the azide with concomitant ring... 

Similarly, but in the cyclic series, the thio-Claisen rearrangement of substrates derived from chiral thiolactams was reported to be facile but poorly stereoselective [129]. The low stereocontrol observed in both cases may be explained by the lack of facial selectivity resulting from the free rotation around the C-N bond of the N,S-ketene acetals. This critical issue has been solved either by constructing a rigid bicyclic framework or by using C2-symmetric amines as chiral inductors. The former strategy, developed by Meyers et al. [45], involved bicycUc thiolactams, which were transformed into N,S-ketene acetals by deprotonation with LDA, followed by S-allylation with various allyl halides (Scheme 9.27). 

Chiral allylic amines constitute key synthetic intermediates, auxiliaries, and resolving agents in the synthesis of both natural and nonnatural products. In 2004, Jamison and Patel reported the first highly enantioselective catalytic synthesis of allylic amines from alkynes, imines, and organobo-ranes such as triethylborane. Catalysed by a chiral complex derived from Ni(cod)2 and chiral ferrocenylphosphine [R)-27, this novel three-component process provided chiral tetrasubstituted allylic amines in good yields in one-pot (Scheme 4.27). These products were obtained in moderate to very good enantioselectivities of up to 89% ee. Both symmetrical and... 

New chiral phosphoramidites were synthesised from chiral un-symmetrical amines and BINOL. The ligands were subsequently applied to the enantioselective hydrosilylation of styrenes.In addition, reports of... 

The design and synthesis of a new class of chiral secondary amines represents a powerful approach to greatly expanding the scope of asymmetric catalysis based on the generation of enamine and iminium ions as a reactive intermediate. Maruoka has made significant contributions to this field of research through the development of a series of binaphthyl-derived, axially chiral C2-symmetric secondary amines of type 17 and 18 (Figure 7.3). 

Treatment of a chiral amine with phosgene is the cheapest way to prepare symmetrical ureas [29]. Nevertheless, due to the toxicity and reactivity of that reagent, it can advantageously be replaced by triphosgene [30] or l,l -carbonyldiimidazole [31-34] or other derivatives such as l,l -carbonyldi-2(lH)-pyridinone [35]. This procedure can be extended to thiophosgene (Scheme 1) and its thio-analogues, such as l,l -thiocarbonyldi-2(lH)-pyridinone to produce thioureas [36] chiral diamines can thus be transformed into the corresponding monoureas or monothioureas. 

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