Amines cyclic /?-fluoro

The next seven references are cited not because of the experimental procedures described but because they indicate diversification in the types of enamines prepared and studied. Both Paquette (25) and Kasper 26) have condensed 2,5-methylene-l,2,5,6-tetrahydrobenzaldehyde (5-nor-bornene-2-carboxyaldehyde) (2) with several cyclic and open-chain aliphatic secondary amines. Kasper studied the ratio of endo to exo aldehyde formed upon hydrolysis of these enamines and the dihydro enamines. Paquette investigated the addition of sulfene to the enamines. -Fluoro-... 

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 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>. 

The 4-fluoro atom of 4,5-difluoro-7-oxo-2,3-dihydro-7//-pyrido[3,2,l-t ]-[2,l]benzoxazine-8-carboxylate (40) was regioselectively substituted by cyclic amines in DMSO at 100-110 C [92JAP(K)92/208288, 92JAP(K)92/ 210656],... 

The substitution of a 4-fluoro atom in 187 (R = Et, R = F) with cyclic amines was unsuccessful at 80-120°C, probably because of the presence of an acidic CH2 group at position 3 [95T11125]. 

Kinetics of reactions of cyclic secondary amines with benzohydrazonyl halides (31) have been measured in benzene51 at 30 °C. The products result from nucleophilic substitution at the halo-carbon via an associative addition-elimination mechanism. For X = Cl or Br, the rate equation has significant terms that are both first and second order in amine, whereas two amine molecules are essential for the fluoro compounds to react. 

Reaction of diacetatoboron chelate 198 with cyclic amines (09USA2009/0156577), 2-aminomethylaziridine (06CCL1431), followed by hydrolysis provided 10-substituted 3(S)-methyl-9-fluoro-7-oxo-2,3-dihydro-7H-pyrido[l,2,3-de][l,4]oxazine-6-carboxylic acids. 

Oxo-2,3-dihydro-5H-pyrido[l,2,3-de][l,4]benzoxazine-3-carbalde-hydes were reacted with tert-bu tyl piperidin-4-ylcarbamate, then the reaction mixture was treated with sodium triacetoxyborohydride to give 3-[4-(ferf-butoxycarbonylamino)piperidin-l-yl)methyl derivatives (08WOP2008/120003). 8-Fluoro-3-oxo-2,3,6,7-tetrahydro-5H-pyrido [l,2,3-cfe][l,4]benzoxazin-7-carbaldehyde was similarly reacted with cyclic amines, then with (polystyrylmethyl)trimethylammonium cya-noborohydride in acidified MeOH (08WOP2008/116815). 

Imagine a cyclic p-fluoro-enone reacting with a secondary amine in a conjugate substitution reaction. The normal addition to form the enolate followed by return of the negative charge to expel the fluoride ion gives the product. 

The 10-fluoro atom of 9,10-difluoro-7-oxo-l//,3/3r,7//-pyrido[3,2,l-iy][3, l]benzoxazine-6-carboxyIic acids was regioselectively substituted by cyclic amines (90EUP373531 96GEP4424369). 

The ability of Al-fluoro amines to undergo reductive defluorination was discovered by Mitsch in 1965. " The treatment of amines 30, 31, and 67 by ferrocene results in the formation of the corresponding cyclic imidoyl fluorides 81, 83, and... 

FIGURE 9.25 Photochemical reactions of cyclic Al-fluoro amines. 

Scheme 6.11 a-Aminations of a-fluoro-P-keto esters and cyclic p-keto esters with a preformed nickel catalyst derived from a diamine ligand. 

Scheme 12.8). In the reaction, N9-substituted 2-halo-6-chloropurine 22 or 28 was captured by a resin at the C6 position. Subsequent substitution at the C2 fluoro/iodo position formed resin 24 or 30. The thiol group on 24 and 30 was then oxidized to give sulfone 25 and 31. 2,6,9-Trisubstituted purine derivatives 26 and 32 were then released by C6 substitution with amines and anilines. This approach allows diverse substitution with primary, secondary, and cyclic amines at the C2 position. With the oxidation of the thiol linker just before the cleavage, only the activated polymer-bound purine intermediates 25 and 31 will be released, thus resulting in high purity of the final product. 

In cyclic amines, such as the protonated form of 3-fluoro-A -methyl-piperidine (21), these interactions provide significant conformational bias [53-55]. In 21, the ring F atom strongly prefers an axial disposition despite experiencing steric compression, with the calculated conformer populations provided in Fig. 6 [55]. As the global minimum, conformer A dominates to the extent of 95-96 %, stabilized by an electrostatic interaction between the F and NH+ moieties, whilst conformer D contributes 4-5 % at equilibrium with the unfavorable diaxial interactions compensated by a productive electrostatic effect. 

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