It is demonstrated that the intramolecular [3+2] cycloaddition of nitrones to alkynes is facile when the length of the tether connecting the two reacting sites is appropriate. The resulting [3+2] cycloaddition products, isoxazolidines, can be further converted into 3-hydroxy-3-pyrrolin2-ones and α-keto-β,γ-unsaturated esters by reductive and oxidative cleavage, respectively. N-[1-methyl-6-(methoxycarbonyl)-5-hexynylidene] methylamine-N-oxide, a ketonitrone which was prepared from the reaction between methyl 7-oxo-oct-2-ynoate and N-methylhydroxylamine, rearranged thermally into two isomeric bicyclic compounds instead of the expected intramolecular [3+2] cycloadduct. An aldonitrone, N-[6-(methoxycarbonyl)-5-hexynylidene]-N-oxide also provided the corresponding rearranged product.
Transformation of the 3-alkylidene cephalosporanic acid derivatives into 3-subsituted cephems was investigated in order to extend the utility of 3-alkylidene cephalosporanic acid derrivatives which were prepared with the aid of samarium(II) iodied. The intramolecular [3+2] cycloaddition reaction via the nitrones derived from the 3-alkylidene derivatives prepared furnished the isoxazolidines, which were converted to the cephams with a hydroxyl group as well as the substituted at 3-position. Synthesis of the 3-substituted-$Δ^3$-cephem was then achieved by treating the 3-hydroxy cephams with excess methanesulfonyl chloride and triethylamine in $CH_2Cl_2$. Also, the transformation of isoxazoline cycloadduct, obtained from the intramolecular [3+2] cycloaddition reaction of the corresponding nitrile oxide derived from the 3-alkylidene cephalosporanic acid derivative, into the $Δ^3$-cephem with a cyclic group as a 3-substituent was successfully carried out.
분자내 [3+2] 알킨-니트론 고리첨가반응은 두 반응자리사이의 길이가 적절할 때 반응이 진행되었다. 분자내[3+2] 고리첨가반응 생성물, 이소옥사졸린, 은 환원성 또는 산화성 N-O 결합 절단으로 각각 3-히드록시-3-피롤린-2-온 과 α-케토β,γ-불포화에스테르로 되었다. 7-옥소-옥틴산 메틸과 N-메틸히드록실아민 반응으로 케토니트론인 N-[1-메틸-6-(메톡시카르보닐)헥신닐리덴]메틸아민-N-옥시드가 생성되었고, 이것은 기대했던 분자내 고리첨가반응생성물이 아니라 열 자리 옮김반응으로 이성질체인 두개의 두고리화합물이 생성된 것이다.
분자내 고리첨가반응의 응용으로서 요오드화사마리움을 사용하여 높은수율로 알킬리덴 세파로스포란 산 유도체를 얻을수 있었다. 3-알킬리덴세팜 니트론의 분자내 고리첨가반응생성물, 이소옥사졸리딘, 을 3-히드록시세팜으로 변화시킨후 과잉 메탄술포닐클로리드와 트리에틸아민을 사용하여 3-치환된 세펨을 성공적으로 얻을수 있었다. 또 3-알킬리덴 세팜의 니트릴 옥사이드의 분자내 고리첨가반응생성물인 이소옥사졸린도 DBU와 트리메틸실란을 사용하여 3-치환된 세펨을 합성할 수 있었다.
