Asymmetric amines

A parallel solution-phase asymmetric synthesis of a-branched amines has been reported by Ellman and coworkers based on stereoselective addition of organomag-nesium reagents to enantiomerically pure tert-butanesulfinyl imines [156]. Micro-wave heating was utilized in two of the steps of this synthesis of asymmetric amines, both for the imine formation and for the resin capture (Scheme 7.128). 

In recent years there has been emerging interest in one-pot asymmetric amination of ketones, but this subject is beyond the scope of this chapter. However, an interesting observation by Borner and coworkers is that different catalysts seem to be required to carry out this process compared to those used for hydrogenation of the corresponding imines or enamines [81, 82]. 

This preparation illustrates a general method for the synthesis of N-methylalkylamines. The submitters have used it to prepare N-methylbutylamine (Note 4) and N-methylallylamine, and the checkers have used it to prepare N-methylisopropylamine (80%), N-methylisobutylamine (67%), N-methyl-fert-butylamine (52%), and N-methyl-2-methoxyethylamine (55%). Secondary amines are useful as starting materials for the synthesis of 1,1-disubsti-tuted hydrazines and asymmetric amine imides. 

A catalytic asymmetric amination reaction has been developed using Cu(2+) catalysts (246). The azodicarboxylate derivative 392 reacts with enolsilanes in the presence of catalyst 269c to provide the adducts in high enantioselectivity, Eq. 213. As observed in the Mukaiyama Michael reactions, alcoholic addends proved competent in increasing the rate of this reaction. Indeed, in the presence of tri-fluoroethanol as additive, the reaction time decreases from 24 to 3 h. 

More recently, Hartwig and coworkers reported iridium-catalyzed, asymmetric aminations of allylic alcohols in the presence of Lewis acid activators [103]. The addition of molecular sieves and Nb(OEt)5 or catalytic amounts of BPh3 activated the allylic alcohol sufficiently to allow allylic amination reactions to occur in high yield, branched-to-linear selectivity, and enantioselectivity (Scheme 29). Without the activators, only trace amounts of product were observed. 

Scheme 9.23 Ir-catalyzed asymmetric aminations of allylic alcohols.

Scheme 9.24 Asymmetric amination of an alcohol according to Carreira et al. [57], 9.4.4...

Hydroxylamine O-sulfonic acid 3p has found wide application in the nonsymmetric and asymmetric amination of organoboron compounds and its use as an amination reagent has been well reviewed . 

A catalytic asymmetric amination of enecarbamates has been attained using a chiral Cu(II) complex of diamine (210) as catalyst. Thus, azodicarboxylates have been shown to react with various enecarbamates (208) derived from aromatic and aliphatic ketones and aldehydes to provide acylimines (209) in good yields with high enantioselectivity (<99% ee). The catalyst loading required for high enantioselectivity was generally low (0.2 mol% in some cases).259... 

Intermolecular asymmetric aminations are at an early stage of development, and consequently much lower turnover frequencies and catalytic yields have been observed at this stage. In the example shown, a key aspect is the activation of the iridium complex catalyst by fluoride ion [111] (Scheme 38). 

Very recently, Jprgensen s group reported the preparation of some chiral nitrido-manganese complexes, which closely resemble those synthesized by the authors group, and the application to asymmetric amination of silyl enol ethers with the chiral complexes using Carreira s method [35], These results were very similar to those of the authors [22]. 

The interpretation remains essentially qualitative for asymmetric amines in which the exact orientation of the principal axes of the electric field gradient remains unknown. 

Scheme 6.11 Reductive asymmetric amination of a-oxo acids with chiral 1-phenylethylamine.

Asymmetric a-amination of enolates has also been described. For example, treatment of a-silyl ketone 109 with LDA followed by addition of oxaziridine 65a gave the A -BOC-amino ketone 110 in 29% yield and 88% de <1998TA3709>. Asymmetric amination of the prochiral enolate of 111 with chiral nonracemic oxaziridine 112 afforded amino ester 113 in 51% yield and 21% de <2001TA535>. 

Electrochemical reduction of coumarin [187] affords the meso and ( ) forms of a product hydrodimerized (at C-4) like many other a,)6-unsaturated acid derivatives. In the presence of tertiary amines, which are not destroyed during the process but catalyze the evolution of hydrogen, a transfer of hydrogen takes place from the amine radical to the coumarin radical with formation of 3,4-dihydrocoumarin. Asymmetric amines cause asymmetric induction during the reduction of 4-methylcoumarin, as in Chapter 26 [188]. 

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

Alkyllithium addition to the (ti -arene) dicarbonylchromium imine chelates has been examined. Treatment of optically pure chelate (41) with methyllithium provides amine (42) with an enantiomeric excess of 94% (Scheme 5). No diastereoselectivity was reported for alkyllithium additions to (arene)tri-carbonylchromium complex (40). In the absence of additional examples, the generality of this chromium chelate methodology for asymmetric amine synthesis cannot be assessed. 

Figure 2.1 The C C bond disconnection approach to asymmetric amine synthesis and a generalized structure of N acyl hydrazones (1).

For secondary, tertiary, and quarternary amines, the naming convention is a bit different, but the suffixes are the same. For symmetrical amines, the di" or "tri" prefix is used depending on whether there are 2 or 3 substituents. For example, dipropylamine or triphenylamine. For asymmetric amines, the parent chain gets the -amine suffix. This name is then prefixed with N- (indicating the nitrogen bond) and the substituent group name, for each substituent, using alphabetic order for tertiary amides. For example, N-ethyl-N-methyl-propylamine, not N-methyl-N-ethyl-propylamine. 

S )-Dibenzyl l-(l-Oxo-l,2,3,4-tetrahydronaphthalen-2-yl)hydrazine-l,2-dicarboxylate (Catalyzed Asymmetric Amination of a Ketone Silyl Enol Ether with an Azo Ester).244 A solution of silver perchlorate (0.040 mmol) and (R)-BINAP (0.048 mmol, 12 mol%) in THF (1 mL) was stirred at room temperature for 30 minutes, cooled to —45°, and treated with dibenzyl azodicarboxylate (0.44 mmol). After stirring for 10 minutes, (3,4-dihydronaphthalen-l-yloxy)trimethylsilane (0.4 mmol) in THF (0.5 mL) was added and the mixture was stirred at —45° for 5 hours. Aqueous HF (20%) and THF (1 1) were added and the mixture was stirred at room temperature for one hour after which time it was made basic with aqueous NaHCC>3 solution and extracted with CH2CI2. 

Closely related to imines are azodicarboxyhc esters. Asymmetric amination is of course an important subject and a report on the utihty of iridium complex 3 is on record. ... 

Pebulate (8), S-propyl butylethylthiocarbamate, is a thiocarbamic acid ester containing an asymmetric amine. Its herbicidal properties have been described by Burt (1959). 

The Merck process group was able to use the Buchwald-Hartwig amination as a means to resolve rac-4,12-dibromo[2.2]paracyclophane 41.86 They report that (5)-[2.2]Phanephos was able to perform a catalytic, asymmetric amination of rac-4,12-dibromo[2.2]paracyclophane 41. This kinetic resolution selectively aminated (42), de-... 

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