Synthesis of medium ring and macrocyclic acetylenic lactones by the ring expansion of oxabicycloalkenones

Journal of the Brazilian Chemical Society

Mahajan, Jaswant Rai¹  University of Brasília, Brasília, Brazil¹  Resck, Inês Sabioni¹ 

关键词: acetylenic lactones;    chloroketolactones;    chlorohydrins;    ring expansion;    tosylhydrazones;    fragmentation reaction;   

DOI  :  10.1590/S0103-50531997000600007

学科分类：化学（综合）

来源: SciELO

【 摘 要 】

Medium ring and macrocyclic lactones are important natural products and we have developed several methods for their synthesis1,2. Thus, in 1990, we described the preparation of desoxydiplodialide D (5) and phoracantholide I (6) from cyclohexane-1,3-dione3 (1) by a novel ring expansion of the vinylogous lactone intermediate 2, as illustrated in Scheme 1.    The success of this new ring enlargement protocol encouraged us to test its scope with several other oxabicycloalkenone systems shown in Scheme 2. While the process worked well with the dihydropyrones 7a,d, affording the corresponding chlorohydrins 8a,d and subsequently the chloroketolactones 9a,d, it was not satisfactory with the phenolic substrates 11 to 14, which failed either to undergo a clean reaction with HOCl or satisfactory ring expansion to the desired chloroketolactone4. Apart from this lack of wide applicability, even in the successful cases (7a,d), the chloroketolactones 9a,d were contaminated with the corresponding chlorohydrins (8a,d) and did not undergo the reductive dechlorination (Zn, AcOH, D or ultrasound)4,5 to the desired ketolactones 10a,d, reverting instead to the starting vinylogous lactones 7a,d.    Aims & Objectives In the face of this failure, instead of looking for alternative methods for the removal of the chlorine atom, we thought it better to exploit its presence for the generation of a regiospecific triple bond according to a method, also under development in our laboratories6, whereby an a-chloroketo function is transformed into an acetylenic linkage, as depicted in Scheme 3. Moreover, it appeared mechanistically feasible to prepare the same acetylenic lactones 15a-d from the chlorohydrin 8a-d, as shown in item C of Scheme 3. Thus, we hoped to obtain the acetylenic lactones 15a-d from the respective mixtures, containing both the chlorohydrin (8a-d) and the chloroketolactone (9a-d).    Apart from this route, we also envisaged preparing the acetylenic lactones 15a-e from the heteroannular and homoannular oxabicycloalkenones (2, 7a-d) via their tosylhydrazones (16a-e), involving a fragmentation reaction patterned after that of the bicycloalkenones7, as illustrated in Scheme 4. These expectations have been largely fulfilled5,8-10 now and herein we describe the details of these investigations.    Results and Discussion When we tried to prepare oxabicyclodecenone 7a by the known procedure11, involving the acylation of 1-morpholinocyclohexene with crotonyl chloride in the presence of triethylamine, followed by hydrolysis and basic isomerization of the resulting probable mixture (Scheme 5; brackets), we obtained only 30% of the desired product 7a, instead of the 73% reported earlier11 . However, on carrying out the isomerization/cyclization under acidic conditions (AcOH:H2O:conc.HCl, 1:1:1), we could raise the yield to 75-80% (see Experimental).    Following this slightly modified procedure, we were also able to improve the yield of oxabicyclohexadecenone 7d from the reported12 16-19% to 30%. Moreover, the melting point of our product, 54-56 °C, is much higher than that described earlier12: 34 °C. However, even this improved procedure gave only poor yields in the

【 授权许可】

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