Electrophilic Oxidative Additions upon 1,4-Dihydropyridines

Lavilla, Rodolfo; Coll, Oscar; Kumar, Rakesh; Bosch, Joan

doi:10.1021/jo971947v

Cited by 33 publications

(9 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These transformations are part of a special class of reactions of dihydropyridines: nonbiomimetic oxidations, which do not lead, as one would expect, to pyridinium salts. [2] Indeed, the electrophiles preferentially react with one of the double bonds of the ene-carbamates 2 than with the proton at C4.…”

mentioning

confidence: 99%

Overall “Pseudocationic” Trifluoromethylation of Dihydropyridines with Triflic Anhydride

et al. 2008

View full text Add to dashboard Cite

Dihydropyridines of type 2 substituted at the C4-position by a carboxylic acid are valuable intermediates for the synthesis of new heterocyclic compounds, including tetrahydropyridinefused d-lactones 3, polysubstituted tetrahydropyridines 4, and piperidine-fused d-lactones 5 (Scheme 1).[1]The starting materials for all those transformations were differently substituted pyridines, which underwent stepwise nucleophilic addition reactions with ketene acetals 1 upon activation by methyl chloroformate. The ring-closure reaction, leading from 2 to 3, is stereospecific: only the transdiaxial-oriented functionalized lactones are formed. These transformations are part of a special class of reactions of dihydropyridines: nonbiomimetic oxidations, which do not lead, as one would expect, to pyridinium salts.[2] Indeed, the electrophiles preferentially react with one of the double bonds of the ene-carbamates 2 than with the proton at C4.The activation of the pyridinium nucleus towards carbon nucleophiles is not limited to alkyl chloroformates or acid chlorides, since several research groups have also used triflic anhydride for that purpose; in addition to the higher stability of the intermediate pyridinium salts and the general higher yields of the addition products, the absence of rotamers at room temperature is also beneficial.[3] For the purpose of comparing the two activation procedures, with methyl chloroformate or triflic anhydride, we synthesized a series of dihydropyridines subsituted by a triflyl group on the nitrogen atom. This led us to the discovery of a new, unexpected transformation of these dihydropyridines.Thus, the reaction of pyridine with ketene acetals 1 a,b (1 equiv) and then with triflic anhydride (1 equiv) at À30 8C led, as expected, after warming the mixture to room temperature and stirring for 17 h, to the same type of acid-substituted dihydropyridines 7 a,b in high yield (97 %, Scheme 2). Although the reaction of these dihydropyridines with either silica gel or an anhydrous solution of HCl in diethyl ether did not lead to the expected lactones 8 a,b, they did react with I 2 and CuBr 2 to give, as for 2, the corresponding halolactones 9 (Scheme 3). [1,4] However, further studies allowed us to discover a new transformation of these dihydropyridines. Indeed, it appeared that the yield of the dihydropyridines 7 a,b was dependent both on the reaction conditions (order of addition, time of reaction) and on the amount of triflic anhydride used with respect to the starting pyridine: no such an influence was observed when methyl chloroformate was used as the activating agent. The use of an excess of triflic anhydride, however, led to the yield of the dihydropyridines decreasing as a function of time. Surprisingly, according to TLC analysis, Scheme 1. Transformations of dihydropyridines.Scheme 2. Preparation of 7.Scheme 3. Formation of lactone 9.

show abstract

mentioning

confidence: 99%

Overall “Pseudocationic” Trifluoromethylation of Dihydropyridines with Triflic Anhydride

et al. 2008

View full text Add to dashboard Cite

show abstract

“…The spectrochemical data [including 1 H-1 H correlation spectroscopy (COSY) and 1 H-13 C correlation experiments] showed a coupling constant pattern between H 2 and H 3 , normally around 2-3 Hz, indicating a trans stereochemistry and preferred conformation with the substituents at positions 2 and 3 being axial. [12] The 1 H NMR spectral data of 5a showed five aromatic protons appeared at 7.58-7.26 as multiplet, a one-proton singlet at 6.68 for C-6 proton, a one-proton doublet at 4.7 (J ¼ 2.7 Hz) for C-2 proton, a one-proton doublet at 3.47 (J ¼ 2.4) for C-3 proton, a three-proton singlet at 3.07 for N-CH 3 group, a two-proton multiplet at 2.90-2.78 for OH, and one C-4 proton and a one-proton doublet at 2.41 (J ¼ 16.8 Hz) for C-4 proton. The IR spectrum showed a peak for the OH group at 3332.39, besides the other usual peaks.…”

Section: Resultsmentioning

confidence: 97%

Stereocontrolled Oxyselenation Studies on 1,4-Dihydropyridines: Synthesis of Trans-2-hydroxy (or Alkoxy) 3-Phenylseleno-1,2,3,4-tetrahydropyridines

Kumar¹,

Kumar²,

Prasad

2011

Synthetic Communications

Self Cite

View full text Add to dashboard Cite

In view of the versatile chemistry and important applications of organoselenium compounds, the introduction of selenium and oxygen functionalities to 1,4-dihydropyridines 4a-d has been achieved. Thus, the natural tendency of 1,4-dihydropyridines 4a-d to undergo biomimetic oxidation to afford pyridinium salts can be switched off through the use of reagents that interact electrophilically with the enamine moiety present in the system. Electrophilic interaction of N-phenylselenophthalimide (N-PSP) with N-alkyl-1,4-dihydropyridines 4a-d in the presence of tetrahydrofuran=H 2 O and alcohol (methanol or ethanol) stereoselectively leads to the corresponding trans-2-hydroxy (or alkoxy) 3-phenylseleno-1,2,3,4-tetrahydropyridines 5a-k in satisfactory yields (40-90%).

show abstract

“…For instance, the oxidative addition of halonium ions (N-halosuccinimide or related alkoxyhalogenations) was investigated, and the method was successful for the preparation of 2-substituted 3-halo-1,2,3,4-tetrahydropyridines, which, in turn, may be considered as valuable synthetic intermediates. 3 In these reactions, we observed the formation of some byproducts, arising from the nucleophilic trapping of the iminium ion produced in the interaction of the enamine moiety with the halogenating agent. We reasoned that the use of nitrogenated species in these processes would result in the formation of interesting tetrahydropyridines bearing amino substituents at positions 2 and 3 (Scheme 1).…”

Section: R' Xmentioning

confidence: 94%

“…Continuing our research on the development of new transformations of 1,4-dihydropyridines, 1 we have recently described some 'non-biomimetic' oxidations of these compounds, in which the normal production of the corresponding pyridinium salt is avoided. [2][3][4] As a consequence, several unusual transformations of these heterocyclic systems have emerged as useful synthetic tools. For instance, the oxidative addition of halonium ions (N-halosuccinimide or related alkoxyhalogenations) was investigated, and the method was successful for the preparation of 2-substituted 3-halo-1,2,3,4-tetrahydropyridines, which, in turn, may be considered as valuable synthetic intermediates.…”

Section: R' Xmentioning

confidence: 99%