Amidines chiral

In addition to the substituents listed in Scheme 1, chiral groups may be introduced and unsymmetrically substituted amidinate anions are also possible. The amidinate anions may also contain additional functional groups, or two such anions can be linked with or without a suitable spacer unit. Yet another variety comprises the amidinate ligands being part of an organic ring system. All these aspects will be covered in the present review. 

Kolb and Barth 229) synthesized oc-substituted optically active amines or amino acids (223). Again the authors employed a derivative of naturally occurring (S)-proline, namely (—)-(S)-l-dimethoxymethyl-2-methoxymethyl-pyrrolidine (221) as chiral auxiliary agent. The metalation of the amidines (160) leads to azaallyl anions homologous with (222). After alkylation and hydrolysis, the desired a-substituted amines and amino acids, respectively, are obtained with some stereoselectivity. 

Meyers, A. I. Dickman, D. A. Absence of an isotope effect on the metalation of chiral form-amidines. The mechanism of asymmetric alkylations leading to chiral amines. J. Am. Chem. Soe. 1987, 109,1263-1265. 

A related example is shown by 4-methoxypyridine activated by a chiral amidine auxiliary, which on attack by a Grignard reagent provides dihydropyridone 134 (Equation 60) <2006OL2985>. Charette and co-workers have nicely developed this methodology to include the asymmetric syntheses of various substituted piperidines and natural products <2005OL2747, 2005JOC2368, 2005OL5773>. 

The development of chiral Diels-Alder reactions to form enantiomerically enriched isoquinuclidines has been of considerable interest. Older examples focused on the use of chiral auxiliaries, generally attached to the nitrogen of the 1,2-dihydropyridine, the best of which were carbohydrate based <1990TL1995>. Recently, amidines have been shown to be very efficient chiral auxiliaries with l-A-amidine-l,2-dihydropyridine 96 undergoing [4+2] cycloaddition with maleic anhydride to give only the endo-product 97 with >95% diastereomeric excess (Equation 4) <2005OL5773>. 

The cyclic sulfates undergo ring opening with a wide variety of nucleophiles, such as hydride, azide, fluoride, benzoate, amines, and Grignard reagents. The reaction of an amidine with a cyclic sulfate provides an expeditious entry to chiral imidazolines 21 and 1,2-diamines (Scheme 9.27).169... 

Imines (98) may be lithiated66 if (a) they have no other acidic protons a to C=N and (b) they are A-methyl imines or they have other activation towards a-lithiation. The N-allyl amidines 99, for example, give interesting chiral organolithiums 100 with BuLi.67... 

The catalytic activation of allylic carbonates for the alkylation of soft car-bonucleophiles was first carried out with ruthenium hydride catalysts such as RuH2(PPh3)4 [108] and Ru(COD)(COT) [109]. The efficiency of the cyclopen-tadienyl ruthenium complexes CpRu(COD)Cl [110] and Cp Ru(amidinate) [111] was recently shown. An important catalyst, [Ru(MeCN)3Cp ]PF6, was revealed to favor the nucleophilic substitution of optically active allycarbonates at the most substituted allyl carbon atom and the reaction took place with retention of configuration [112] (Eq. 85). The introduction of an optically pure chelating cyclopentadienylphosphine ligand with planar chirality leads to the creation of the new C-C bond with very high enantioselectivity from symmetrical carbonates and sodiomalonates [113]. 

Amidines, N-(l,2,4-thiadiazol-5-yl)-, rearrangement, 56, 103 Amidoximes, 1,2,4-oxadiazol-3-yl-, rearrangements, 56, 55 Amidyl radicals, see Radicals, nitrogen Amination, asymmetric, of carboxylic acids by chiral nitroso compds, 57, 41 Amines, catalysis of 3-acyl-1,2,4-oxadiazole arylhydrazone rearrangement by, 56, 87 Amines, thionitroso-, formation, 55, 20 Aminium cation radicals, see Radicals, nitrogen... 

High enantioselectivity is also possible in these reactions by using an optically active amidine, readily available from (S)-valinol. A recent synthesis of ( -)-reticuline made degant use of this chiral intermediate (equation 26). ° Likewise, (-)-yohimbone was prepared in 98% enantiomaic excess using these reactions. ... 

The mechanism of the deprotonation of dipole-stabilized anions has been studied in detail. It has been shown by IR spectroscopy that a preequilibrium exists between the butyllithium base and the amide or amidine, forming a coordination complex prior to deprotonadon. A recent mechanistic study has shown that, in cyclohexane solvent, this prior coordination is between the amide (or added TMEDA) and aggregated s-butyllithium, and that the effect of the coordination is to increase the reactivity of the complex. The diastereoselectivity of proton removal in chiral benzylic systems has also been examined,but since the anions invert, this selectivity is of little consequence in the alkylation step. 

Yamada T, Lukac PJ, Yu T, Weiss RG (2007) Reversible, room-temperature, chiral ionic liquids. Amidinium carbamates derived from amidines and amino-add esters with carbon dioxide. Chem Mater 19 4761-4768... 

It is likely that CN" adds reversibly at the imine center. Other studies would indicate that there is little preference for addition on one side of the planar chelate relative to the other, even though the Co(III) center is chiral. The stabilities of analogous amino acid complexes (5) and the reduction of the chelated imine by the BHi,- ion both show little specificity (20). However, the subsequent reaction of coordinated amide ion with the amino acid nitrile is another matter. Once formed, the amidine quadridentate is stable in dilute acid and base. Moreover, the least stable configuration is the preferred product. The strain in the bound amidine moiety -CH2-N = C(NH2)-C- for this isomer is much greater than that in the kinetically less-preferred product where the amidine moiety -CH2-N = C(NH2)-C- is close to being planar. The strain difference is reflected in the equilibrium position for the two isomers which lies heavily towards the isomer least favored by the kinetic route. 

Some racemic compounds might be separated without the need to make chemical derivatives. Chiral diols bond selectively (55-isomer favored over the i i -isomer by a factor of 6 or 7) by hydrogen bonding to the amidine (10.28).56... 

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