Reductive aminations ketones

For an example of another chiral ketone reductively aminated with Ti(OiPr)4 or Al (OiPr)3 with hydride reagents, see Dhainaut, J., Leon, P., Lhermitte, F., and Oddon, G.(May 2003) A process which is... 

Reductions of aromatic carbonyl compounds a-substituted carbonyl compounds a-hydroxy ketones p- and y-substituted carbonyl compounds ketones and a- and p-diketones P-keto acids and esters, y-kcto esters masked carbonyl compounds activated double bonds (hydrogenation) acyclic and cyclic ketones reductive amination of keto acids BY BY BY, glycerolDH BY BY, An, Cr, Cu, Gc, Ha, Ks, Mi, Mr, Ns, Pd, Pm, Rn, Y1 BY, Ao, Cb, Cg, Cu, Ct, Gc, Hp, Lk, Mj, Pf, Pm, Pv, Rr, Td, glycerolDH BY BY, An, Gc, Pc HLADH, TBADH, other ADHs, HSDHs AADH, GluDH, PheDH... 

SET reduction of ketones Reductive amination Reductive coupling of imines Reformatsky reaction Ring-opening of strained heterocycles... 

Method I. This procedure is used for most ketone reactions. A representative example is the reductive amination of cyclopenta-none [P2P] with hexamethyleneimine [MeNHa] Hexamethyl-eneamine (I.Og, lOmmol) and cylclopentanone (0.84g, lOmmol) were mixed in 1,2-dichloroethane (35mL) and then treated with... 

Anyway, there have been two very hot topics in chemistry lately clay microwaves. Both have been shown to do remarkable things in preparative organic chemistry. And this article Strike has [58], has combined both to produce some stunning reductive ami-nations of ketones to final amine products. The procedure involves mixing naked ketone, the amine, some clay and some NaBH4 in a beaker and zapping it in the microwave for only a couple of minutes. That s it. The general procedure is as follows ... 

Methamphetannne is a notorious street drug One synthesis involves reductive amination of benzyl methyl ketone with methylamine What is the structure of methamphetamine ... 

Sodium cyanoborohydride is remarkably chemoselective. Reduction of aldehydes and ketones are, unlike those with NaBH pH-dependent, and practical reduction rates are achieved at pH 3 to 4. At pH 5—7, imines (>C=N—) are reduced more rapidly than carbonyls. This reactivity permits reductive amination of aldehydes and ketones under very mild conditions (42). 

The zwitterion (6) can react with protic solvents to produce a variety of products. Reaction with water yields a transient hydroperoxy alcohol (10) that can dehydrate to a carboxyUc acid or spHt out H2O2 to form a carbonyl compound (aldehyde or ketone, R2CO). In alcohoHc media, the product is an isolable hydroperoxy ether (11) that can be hydrolyzed or reduced (with (CH O) or (CH2)2S) to a carbonyl compound. Reductive amination of (11) over Raney nickel produces amides and amines (64). Reaction of the zwitterion with a carboxyUc acid to form a hydroperoxy ester (12) is commercially important because it can be oxidized to other acids, RCOOH and R COOH. Reaction of zwitterion with HCN produces a-hydroxy nitriles that can be hydrolyzed to a-hydroxy carboxyUc acids. Carboxylates are obtained with H2O2/OH (65). The zwitterion can be reduced during the course of the reaction by tetracyanoethylene to produce its epoxide (66). 

Cycloahphatic amine synthesis routes may be described as distinct synthetic methods, though practice often combines, or hybridi2es, the steps that occur amination of cycloalkanols, reductive amination of cycHc ketones, ring reduction of cycloalkenylarnines, nitrile addition to ahcycHc carbocations, reduction of cyanocycloalkanes to aminomethylcycloalkanes, and reduction of nitrocycloalkanes or cycHc ketoximes. 

Amin omethyl-3,5,5-trimethyl cyclohexyl amine (21), commonly called isophoronediamine (IPD) (51), is made by hydrocyanation of (17) (52), (53) followed by transformation of the ketone (19) to an imine (20) by dehydrative condensation of ammonia (54), then concomitant hydrogenation of the imine and nitrile functions at 15—16 MPa (- 2200 psi) system pressure and 120 °C using methanol diluent in addition to YL NH. Integrated imine formation and nitrile reduction by reductive amination of the ketone leads to alcohol by-product. There are two geometric isomers of IPD the major product is ds-(22) [71954-30-5] and the minor, tram-(25) [71954-29-5] (55). 

Reductive amination ol aldehydes or ketones by cyanoborohydride (or tnacetoxyborohydride) anion Selective reduction of carbonyls to alcohol, oximes to N alkylhydroxylarmnes, enamines to amines... 

Reductive amination (Section 22.10) Reaction of ammonia or an amine with an aldehyde or a ketone in the presence of a reducing agent is an effective method for the preparation of primary, secondary, or tertiary amines. The reducing agent may be either hydrogen in the presence of a metal catalyst or sodium cyanoborohy-dride. R, R, and R" may be either alkyl or aryl. 

Reductive amination (Section 22.10) Method for the preparation of amines in which an aldehyde or a ketone is treated with ammonia or an amine under conditions of catalytic hydrogenation. 

A variation on this theme consists in first displacement of the chlorine in 73 with ethylaminoethanol. Reductive amination of the ketone by means of ammonia in the presence of hydrogen gives the hydroxylated diamine (77). Use of this intermediate to effect displacement of the halogen at the 4 position of 70 affords hydroxychloroquine (78). ... 

Amines can be synthesized in a single step by treatment of an aldehyde or ketone with ammonia or an amine in the presence of a reducing agent, a process called reductive amination. For example, amphetamine, a central nervous system stimulant, is prepared commercially by reductive amination of phenyl-2-propanone with ammonia, using hydrogen gas over a nickel catalyst as the reducing agent. 

Active Figure 24.4 MECHANISM Mechanism of reductive amination of a ketone to yield an amine. Details of the imine-forming step were shown in Figure 19.8 on page 711. Sign in afwww.thomsonedu.com to see a simulation based on this figure and to take a short quiz. 

The reductive amination of ketones can be carried out under hydrogen pressure in the presence of palladium catalysts. However, if enantiopure Q -aminoketones are used, partial racemization of the intermediate a-amino imine can occur, owing to the equilibration with the corresponding enam-ine [102]. Asymmetric hydrogenation of racemic 2-amidocyclohexanones 218 with Raney nickel in ethanol gave a mixture of cis and trans 1,2-diamino cyclohexane derivatives 219 in unequal amounts, presumably because the enamines are intermediates, but with excellent enantioselectivity. The two diastereomers were easily separated and converted to the mono-protected cis- and trans- 1,2-diaminocyclohexanes 220. The receptor 221 has been also synthesized by this route [103] (Scheme 33). 

One route is by reductive amination of ketone (10) available by Friedel-Crafts reaction from acid (11) which we can make by an FGA strategy (Chapter T 24). 

Sodium triacetoxyborohydride is an alternative to NaBH3CN for reductive amination. This reagent can be used with a wide variety of aldehydes or ketones with primary and secondary amines, including aniline derivatives.93 This reagent has been used successfully to alkylate amino acid esters.94... 

Zinc borohydride has been found to effect very efficient reductive amination in the presence of silica. The amine and carbonyl compound are mixed with silica and the powder is then treated with a solution of Zn(BH4)2. Excellent yields are also obtained for unsaturated aldehydes and ketones.96... 

Besides direct reduction, a one-pot reductive amination of aldehydes and ketones with a-picoline-borane in methanol, in water, and in neat conditions gives the corresponding amine products (Scheme 8.2).40 The synthesis of primary amines can be performed via the reductive amination of the corresponding carbonyl compounds with aqueous ammonia with soluble Rh-catalyst (Eq. 8.17).41 Up to an 86% yield and a 97% selectivity for benzylamines were obtained for the reaction of various benzaldehydes. The use of a bimetallic catalyst based on Rh/Ir is preferable for aliphatic aldehydes. 

Amines can be synthesized by the treatment of a ketone or aldehyde with an amine in the presence of hydrogen and a noble metal catalyst. During this reductive amination, the intermediate loses water to give an imine that is reduced to yield the amine product (Scheme 5.4). 

Among the anionic/reduchve domino transformations, one of the most often encountered is the reductive amination of a carbonyl compound being followed by the formation of a lactam. As did many others before, Abdel-Magid and coworkers used this approach for the synthesis of y- and 6-lactams as 2-949 from either ketone 2-944 and amine 2-945 or amine 2-946 and ketone 2-947 via 2-948, employing sodium triacetoxyborane (Scheme 2.212) [484]. 

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