Cyclic amines reactions

Other papers of interest in this section report transamination of camphor-3-carbothioamides with secondary cyclic amines, reaction of camphorquinone with dimethyl /S-ketoglutarate, the use of fenchone (212 X=0) in alkene formation from Grignard reagents, bromination of 2-e/itfo-6-endo-dibromobornane to yield 2,3,6-endo-tribromoborn-2-ene, and camphor-enol trimethylsilyl ether formation by quenching the reaction mixture of butyl-lithium and camphor tosyl-hydrazone with trimethylsilyl chloride. ... 

Other noncyclic reactions are observed, especially in polyamides of longer carbon chain monomers for example, the linear analogue to the cyclic amine reaction is diamine coupling (eq. 10) to form secondary amines that can act as branch points (eq. 11). 

The intemiolecular reaction described above has been extended to intramolecular displacement leading to cyclic amines. Reaction of allylic alcohols with morpholine in the presence of a nickel catalyst has also been reported. ... 

In Diels-Alder reactions a nitroolefin may function as an electron-deficient ene com-onent or a 1,2-dihydropyridine derivative may be used as a diene component. Both types of iactants often yield cyclic amine precursors in highly stereoselective manner (R.K. Hill, 1962 i. BOchi, 1965, 1966A). 

The reaction of the vinylcyclopropanedicarboxylate 301 with amines affords an allylic amine via the 7r-allylpalladium complex 302[50]. Similarly, three-membered ring A -tosyl-2-(l,3-butadienyl)aziridine (303) and the four-mem-bered ring azetidine 304 can be rearranged to the five- and six-membered ring unsaturated cyclic amines[183]. 

Experiments designed to clarify the situation were carried out by Wittig and Mayer (40). It was shown that changing the molar ratio of amine (diethylamine, di- -butylamine, or diisobutylamine) to -butyraldehyde from 1 1 to 2 1 did not affect the yield of enamine (53- 64%, based on the aldehyde). Contrariwise, changing the ratio of amine (morpholine, piperidine, or pyrrolidine) to n-butyraldehyde from 1 1 to 2 1 boosted the yields from 52-57 % to 80-85 %. The authors interpret these data as indicating that the cyclic amines form aminals with n-butyraldehyde, while the open-chain do not. Infrared evidence is stated as having shown that the aminal originates not from attack of excess amine on the enamine, which is stable under the conditions of the reaction, but from the N-hemiacetal (17). 

Selective hydrolysis of the 3-carboxylate with 6N-HCl/AcOH was unsuccessful and instead the 4-carboxylate hydrolyzed to the corresponding acid, however, heating of 432 at 50 °C caused its hydrolysis and decarboxylation in one step. Subsequent reaction with either MnO or DDQ gave 433. The fluorine atom at 8-position could be replaced by cyclic amines to give the 8-pyrrolyl or 8-[l-methyl-4-piperazinyl] derivatives 436 which upon hydrolysis using either acidic or basic conditions afforded the... 

Reaction of 9,10-difluoro-7-oxo-2,3-dihydro-7//-pyrido[l, 2,3- e]-1,4-ben-zothiazine-6-carboxylic acid and its ethyl ester with B(OH)3 in AC2O in the presence of ZnCl2 afforded 6-[(diacetoxyboryl)oxycarbonyl] derivative 323 (R = OAc)], which was reacted with primary and cyclic amines to give 10-amino-9-fluoro-7-carboxylic acid derivatives 324 (97MI41, 98MI30). 6-[(Difluoroboryl)oxycarbonyl derivative 323 (R = F) was obtained from ethyl 9,10-difluoro-7-oxo-2,3-dihydro-7//-pyrido[l,2,3- fe]-l,4-benzothiazine-6-carboxylate with BF3-THF complex. Reaction of 323 (R = F) and 1-methylpiperazine in DMF at 50-60 °C and subsequent acidic hydrolysis afforded 7 (97MI1). 

The reaction is effective with both acyclic and cyclic amides., or lactams, and is a good method for preparing cyclic amines. 

The net effect of the Stork reaction is the Michael addition of a ketone to an cn/3-unsaturated carbonyl compound. For example, cyclohexanone reacts with the. cyclic amine pyrrolidine to yield an enamine further reaction with an enone such as 3-buten-2-one yields a Michael adduct and aqueous hydrolysis completes the sequence to provide a 1,5-diketone (Figure 23.8). 

Reduction of iV-(3-bromopropyl) imines gives a bromo-amine in situ, which cyclizes to the aziridine. Five-membered ring amines (pyrrolidines) can be prepared from alkenyl amines via treatment with N-chlorosuccinimide (NCS) and then BusSnH. " Internal addition of amine to allylic acetates, catalyzed by Pd(PPh3)4, leads to cyclic products via a Sn2 reaction. Acyclic amines can be prepared by a closely related reaction using palladium catalysts. Three-membered cyclic amines (aziridines)... 

When enamines are treated with alkyl halides, an alkylation occurs that is analogous to the first step of 12-14. Hydrolysis of the imine salt gives a ketone. Since the enamine is normally formed from a ketone (16-12), the net result is alkylation of the ketone at the a position. The method, known as the Stork enamine reaction is an alternative to the ketone alkylation considered at 10-105. The Stork method has the advantage that it generally leads almost exclusively to monoalkylation of the ketone, while 10-105, when applied to ketones, is difficult to stop with the introduction of just one alkyl group. Alkylation usually takes place on the less substituted side of the original ketone. The most commonly used amines are the cyclic amines piperidine, morpholine, and pyrrolidine. 

Reaction between aldehydes and ammonia (cyclic amines)... 

Tne kinetic advantages of five-membered rings over other izes are well illustrated by the radical reaction leading to cyclic amine (3) used on p T 247. Chlori-... 

The same catalytic system has been tested for the hydroamination of 1,3-butadiene with cyclic amines from the three-membered ring aziridine to the seven-mem-bered ring perhydroazepine. Although arizidine does not lead to a hydroamination reaction, all other cyclic amines give rise to a mixture of 1 1 telomers in fair to excellent yields (e.g., Eq. 4.47) [181]. 

Each of the unsaturated cyclic amines shown below has been synthesized by reaction of an amino-substituted allylic silane under iminium ion cyclization conditions (CH2=0, TFA). By retrosynthetic analysis, identify the appropriate precursor for each cyclization. Suggest a method of synthesis of each of the required amines. 

In order to overcome these two issues, we reversed the order of the reaction sequence, as summarized in Scheme 1.20. We took advantage of the alcohol functional group in 50. Oxidation ofpMB of 50 with DDQ proceeded smoothly to form cyclic aminal 52 (as a mixture of a and P = 11.5 1) in toluene at 0-10 °C. The resulting DDQH, which is insoluble in toluene, was filtered off, and isolated DDQH could be recycled as we demonstrated in the Proscar process (see p. 92) [32]. Thus, this process minimizes the impact to the environment from an oxidizing reagent. Cyclic aminal 52 was solvolyzed with NaOH in MeOH at 40 °C. The resulted anisaldehyde was reduced in situ to pMBOH 43 by addition of NaBH4 and the desired amino alcohol 53 was isolated by direct crystallization from the reaction mixture, upon neutralization with acetic acid, in 94% yield and >99.9% ee after crystallization from toluene-heptane. 

Helmchen and coworkers employed a,co-amino-1,3-dienes as substrates [51]. By using palladium complexes with chiral phosphino-oxazolines L as catalysts, an enantiomeric excess of up to 80 % was achieved. In a typical experiment, a suspension of Pd(OAc)2, the chiral ligand L, the aminodiene 6/1-90 and an aryltriflate in dimethylformamide (DMF) was heated at 100 °C for 10 days. Via the chiral palladium complex 6/1-91, the resulting cyclic amine derivative 6/1-92 was obtained in 47% yield and 80% ee (Scheme 6/1.23). Using aryliodides the reaction time is shorter, and the yield higher (61 %), but the enantiomeric excess is lower (67% ee). With BINAP as a chiral ligand for the Pd°-catalyzed transformation of 6/1-90 and aryliodide, an ee-value of only 12% was obtained. 

The ten-membered cyclic amine 106 was efficiently prepared from quionolizidine derivative 105 by methylation to a nonisolated intermediate followed by an olefin-forming desulfonylation reaction induced by treatment with sodium amalgam (Scheme 11) <20010L2957>. 

The substitution, with cyclic amines, of a 4-fluoro atom in 50 (R= Et, R1 = F) was unsuccessful at 80-120 °C, probably because of the presence of an acidic CH2 group at position 3 <1995T11125>. 3-Decarboxylated products 50 (R = Et) were prepared from 49 (R = Et) under different reaction conditions (Equation 7) < 1995T11125>. Direct conversion of 49 (R= Et R1 = Et, allyl) to acid 50 (R = H, R1 = F) was achieved in a boiling mixture of AcOH-conc. HC1 <1995T11125>. 

With the exception of intramolecular amination reactions, all of the early aryl halide aminations were catalyzed by palladium complexes containing the sterically hindered P(o-tol)3. In papers published back-to-back in 1996, amination chemistry catalyzed by palladium complexes of DPPF and BINAP was reported.36,37 These catalysts allowed for the coupling of aryl bromides and iodides with primary alkyl amines, cyclic secondary amines, and anilines. 

An expeditious microwave assisted SNAr reaction with cyclic amines has been reported for activated aromatic substrates [83] (Eq. 29). 

Considerable interest remains in catalyzed hydrogen-transfer reactions using as donor solvents alcohols, glycols, aldehydes, amides, acids, ethers, cyclic amines, and even aromatic hydrocarbons such as alkylben-... 

---