Карцев В.Г.Избранные методы с-за и модифик. гетероциклов т.1 , 2003

A mechanistic explanation for the observed cis and trans stereoselectivity is also proposed and discussed. These compounds appear to be potentially useful as Michael acceptors and activated dienophiles. In fact, lithiated 2-(1-chloroethyl)-4,4-dimethyl-2- oxazoline 2, readily available from 1, adds to symmetric electron-deficient alkenyl heterocycles to afford substituted cyclopropanes 3–6 in very good yields [14].

3Het = 2-pyridyl (95%)

4Het = 4-pyridyl (93%)

5Het = 2-(4,4,6-trimethyl)-5,6-dihydro-4H-[1,3]-oxazinyl (62%)

6Het = 2-(4,4-dimethyl)oxazolinyl (95%)

The addition proceeds stereospecifically: only the stereoisomer setting the two heteroaryl rings trans on the cyclopropane ring forms. The addition reaction of 2 to asymmetric electron-lean alkenes is instead stereospecific with reference to the geometry of the starting alkene but there is no stereoselection as far as the newly created stereogenic center. A route to chiral non-racemic heterosubstituted cyclopropanes, starting from optically active 2-chloromethyl-2-oxazolines, has also been studied [14].

2. Stereoselective synthesis of [1,2]-oxazetidines and isoxazolidin-5-ones

A promising synthesis of [1,2]-oxazetidines and isoxazolidin-5-ones has been developed [13]. Treatment of the 2-(1-chloro-1-lithioethyl)-4,4-dimethyl-2-oxazoline 2 at low temperature (–98°C) with nitrones furnishes diastereomeric spirocyclic compounds 7a, 7b in relative amounts that depended on the reaction time. Upon quenching the reaction (warm-up to room temperature), [1,2]-oxazetidines 8 were isolated highly stereoselectively through a stereoelectronically allowed ring-contraction process.

3. Stereospecific synthesis of α,β-epoxy-γ-butyrolactones

Our continuing involvement in the chemistry of heterocyclic systems and as of oxiranyl anions [4, 5] led us to considering the possibility that the chemistry of the oxazoline system combined with the oxiranyl anion-based methodology might be exploited for the preparation of α,β-epoxy-γ-butyrolactones which are versatile intermediates in synthetic organic chemistry as they intervene in synthetic routes to precursors of natural produts such as epolactaene [15], which has a potent neurite outgrowth activity in a human neuroblastoma cell line SH-SYS5, and (+)-cerulenine [16], a potent fungal inactivator of fatty acid synthetase. This kind of compounds could be synthesized via a preliminary stereospecific β-lithiation of β-aryl-substituted oxazolinyloxiranes 14 [17]. The trapping reaction of such reactive intermediates 15, stable at low temperature for hours, with carbonyl compounds gave highly diastereoselectively the corresponding spirocyclic oxazolidines 17 as a result of a nucleophilic attack of the intermediate alkoxides 16 on the re face of the oxazoline moiety; the latter could quantitatively be converted into α,β- epoxy-γ-butyrolactones 18 upon treatment with 2% w/w oxalic acid.

The present oxazolinyloxiranyl anion-based methodology to epoxylactones was also successfully extended to the preparation of optically pure α,β-epoxy-γ-butyrolactones 20 starting from the chiral non-racemic 2-chloromethyl-2-oxazoline 19.

A substituent effect was observed: the oxiranes bearing electron-withdrawing groups in the aryl group isomerized faster than those with electron-donating groups.

References

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3.Capriati V., Degennaro L., Florio S., Luisi R., Tralli C., Troisi L., Synthesis 2001 15 2299.

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13.Capriati V., Degennaro L., Florio S., Luisi R., Eur. J. Org. Chem. 2002 2961.

14.Rocchetti M.T., Fino V., Capriati V., Florio S., Luisi R., J. Org. Chem. 2002 0000.

15.Kuramochi K., Itaya H., Nagata S., Takao K., Kobayashi S., Tetrahedron Lett. 1999 40 7367.

16.Mani N.S., Townsend C.A., J. Org. Chem. 1997 62 636.

17.Södergren M.J., Andersson P.G., J. Am. Chem. Soc. 1998 120 10760.

18.Nilsson Lill S.O., Arvidsson P.I., Ahlberg P., Tetrahedron: Asymmetry 1999 10 265.

19.Perna F.M., Capriati V., Florio S., Luisi R., J. Org. Chem. 2002 67 8351.

20.Perna F.M., Capriati V., Florio S., Luisi R., Tetrahedron Lett. 2002 43 7739.

ноидов; о синтезе конденсированных азотсодержащих гетероциклических систем на основе 3-гетарилхромонов путем аннелирования гетероциклического фрагмента по связи С(2)-С(3) пиронового и по связям С(5)-С(6), С(6)-С(7), С(7)-С(8) хромонового циклов; о реакциях рециклизации модифицированных флавоноидов и о способах распознавания строения продуктов, образующихся в их результате; о систематическом исследовании химических и биологических свойств модифицированных флавоноидов и выявлении среди них новых высокоэффективных лекарственных препаратов широкого спектра биологического действия. А также рассмотрены аспекты функционализации флавоноидов такими фармакоформными группами, как аминокислоты, олигопептиды, карбоновые кислоты, амины, углеводы, ядра пяти- и шестичленных гетероциклов и аренов.

OMe

Доклад сделан по материалам обзоров: "Синтез флавонов и 2-гетарилхромонов", "Синтез 3-арил- и 3-гетарилхромонов" и "Гетарилкумарины: методы синтеза", полные тексты которых опубликованы в кн. "Избранные методы синтеза и модификации гетероциклов", под ред. Карцева В.Г., М.: IBS PRESS, 2003, т. 2, с. 193, c. 503, c. 518.

Схема 2

Следует добавить, что этиловый эфир 2-этоксиметиленпентафторбензоилуксус- ной кислоты 7 аналогично эфиру 1а циклизуется в 5,6,7,8-тетрафтор-3-этоксикарбо- нилхромон 8а [1, 2] (схема 3).

Схема 3

Хромоны 3а и 8а легко гидролизуются до соответствующих кислот 3с и 8b (схема 4). Последние при нагревании декарбоксилируются с образованием 5,6,7,8- тетрафторхромона 9 [1, 2].