Carbonyl compounds reactions with amines

The successful synthesis of 2-thienyl and substituted 2- and 3-thienyl-acetylenes in yields as high as 60-80% opened a wide variety of synthetic applications. Various addition reactions with carbonyl compounds or epoxides could be carried out with ease. Aliphatic as well as aromatic amine addition reactions, or condensation reactions with hydrazine or hydroxylamine could be easily performed. 

Resin-bound amines can be converted into imines [710,711] or enamines by reaction with carbonyl compounds (Entries 6 and 7, Table 3.39). Resin-bound enamines have also been prepared by Michael addition of resin-bound secondary amines to acceptor-substituted alkynes [712], by Hg(II)-catalyzed addition of resin-bound secondary amines to unactivated alkynes [713], by addition of C-nucleophiles to resin-bound imino ethers [714], and by chemical modification of other resin-bound enamines [712,713,715], Acceptor-substituted enamines ( push-pull alkenes) are not always susceptible to hydrolytic cleavage by TFA alone and might require aqueous acids to undergo hydrolysis [716]. 

More general solutions come from the replacement of alkylations by reactions with carbonyl compounds. These generally occur once only and in many cases cannot occur twice as the products—amides 12 or imines 15 for example—are much less nucleophilic than the starting amine. The products are reduced to the target amines. The amide route is restricted to amines with a CH2 group next to nitrogen 13 but the imine route is very general and is known as reductive animation.1 It is the most important way to make amines and a recent survey showed that the majority of amines made in the pharmaceutical industry are made this way. 

Elimination. ( , )-1,3-Dienamines are obtained from (Z)-4-methoxy-2-aIkenyl-amines by treatment with BuLi (or NaHMDS). Elimination of MeOH is stereoselective. A preparation of trifluoromethylallenes from l,l-dichloro-3,3,3-trifluoropropen-2-yl tosylate involves treatment with BuLi to generate lithium 3,3,3-trifluoropropynide, which is used for reaction with carbonyl compounds and then Negishi coupling. ... 

AUylations. A direct preparation of accomplished by treatment with SnCl,. Allytnl for reaction with carbonyl compounds and imu can also be used as allylating agents for amine... 

The Pictet-Spengler reaction is a modification of the Bischler-Napieralski reaction. It is probably the most used method for the synthesis of 1,2,3,4-tetrahydro isoquinoline core. Therefore, phenylethyl amines are used in reaction with carbonyl compounds in the presence of protic or Lewis acids. 

The degradation of carboxylic acid has been used for the preparation of amines, amino acids, and structural elucidation, especially via labeling. The reaction with carbonyl compounds has an even wider application in organic synthesis. 

There have been a few reports on the simple route to enamidines offerred by the Peterson reaction. Lithiation of a-silyl amidines such as 66 with Bu Li and subsequent Peterson reaction with carbonyl compounds gives the corresponding enamidines 67 (Scheme 2.42) [106,107). The enamidines 67 are converted to the amines by treatment with sodium borohydride in ethanol under slightly acidic conditions. These entire homologation processes can be performed without purification of the enamidine intermediates 67. 

Primary and secondary amines also react with epoxides (or in situ produced episulfides )r aziridines)to /J-hydroxyamines (or /J-mercaptoamines or 1,2-diamines). The Michael type iddition of amines to activated C—C double bonds is also a useful synthetic reaction. Rnally unines react readily with. carbonyl compounds to form imines and enamines and with carbo-tylic acid chlorides or esters to give amides which can be reduced to amines with LiAlH (p. Ilf.). All these reactions are often applied in synthesis to produce polycyclic alkaloids with itrogen bridgeheads (J.W. Huffman, 1967) G. Stork, 1963 S.S. Klioze, 1975). 

A study of the reactions of butadiene, isoprene, or allene coordinated to nickel in a metallacycle, with carbonylic compounds, has been reported by Baker (example 11, Table IV). In the presence of phosphines, these metallacycles adopt a cr-allyl structure on one end and a ir-allyl structure on the other, as mentioned in Section II,A,1. The former is mainly attacked by aldehydes or electrophilic reagents in general, the latter by nucleophiles (C—H acids, see Table I, or amines, see Table IX). 

A one pot formation and purification of a 5-arylidine 4-thiazolidinone library has also been reported using polymer scavenging as the principle method of purification. An automated synthesizer was employed to make a parallel array of 4080 4-thiazolidinones, prepared simultaneously from a 3-component condensation of mercaptoacetic acid with an amine and a carbonyl compound. Further structural decoration was then introduced using the libraries from libraries principle where the core template was derivatized via an aldol reaction with a second carbonyl unit at the 5-methylene position (Scheme 2.57) [84]. After both synthetic steps. 

Ugi, I. and Steinbruckner, C. (1961) Isonitriles. II. Reaction of isonitriles with carbonyl compounds, amines, and hydrazoic acid. Chem. Ber. 94, 734-742. 

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