Stepwise Metathesis A promising strategy in organic synthesis Goverdhan Mehta University of Hyderabad, Hyderabad 500001, India
Olefin metathesis is a remarkable catalytic reaction in which olefins undergo bond reorganization leading to a redistribution of alkylidene moieties (eqn. 1) (1-6). The reaction is fairly common, can he induced by a variety of homogeneous and heterogeneous catalysts (derived from tungsten, molybdenum, rhenium, and aluminium), and has many varied chemical applications (14). Conversion of propene to ethene and 2hutene, preparation of linear polyalkenamers (eqn. 2) from cyclic olefins, and fatty acid ester metathesis (eqn. 3) are typical utilitarian examples. However, extensive synthetic applications of the catalyzed metathesis reaction
have been hampered due to random scrambling of alkylidene moieties, uncertain product distribution, and exacting reaction conditions (1-9). A new metathetic approach that circumvents these difficulties and is synthetically attractive is suggested by the conventional mechanism (eqn. 4) of the catalyzed olefin metathesis reaction. Although, the carbene mechanism (one carbon chain extension, eqn. 5) is currently favored over the "pair wise" exchange of carbons (eqn. 41,
the latter does provide a clue to the role of cyclobutane intermediates in carrying out controlled, stepwise olefin metathesis. As cyclobutanes are readily accessible (10-12) through a symmetry allowed photochemical ~ 2 s s2s addition of olefins and are also prone to thermal fragmentation, the two-step metathetic sequence (eqn. 6)presents interesting synthetic possibilities in assembling diverse organic molecules. However, despite the conceptual
+
simplicity and promise of sequential metathesis as a viable synthetic strategy, there has been only limited exploitation of this methodology and that, too, very recently. The purpose of this brief article is to stimulate interest in metathetical approaches to diverse organic molecules and to highlight some of the recent attainments in this area. Scheme 1,partly illustrates the scope of the two-step metathesis sequence enumerated above (eqn. 6). Each step of the metathesis operation, i.e., photocycloaddition to form cyclobutanes and their thermal or catalyzed fragmentation to two ethylenic components can he carried out either intra- or intermolecularly. Thus, i t should be possible (in principle) to conduct a variety of diverse skeletal changes of synthetic value like C-C bond formation, homologation, degradation, cyclization, ring fission, ring expansion, ring contraction, and transposition, etc., the metathetic way, by simply altering the structures of the starting olefinic partners. Add to this the fact Scheme 1 Intermediate Starting Olefins
cycloadditi~n prcducl
Metathesis
prcduct
J
s~@em Volume 59 Number 4
April 1982
313
that intermediate cyclohutanes can be obtained readily uia photochemical route (10-12) from alkenes, alkynes, dienes, aromatics, u,&unsaturated ketones and carboxylic acids, quinones, pyrones, etc., and one has a truly versatile reaction and fu~lct~onal \,;innrepresenting a pantmmn ~~t'sfrucfural ticm.;. T h e incorporation d'fnnctimal CrOUDS into the olefinic components not only provides a useful handle for further manipulation hut also gives the metathetic process a regiochemical bias and in many cases reduces the refractoriness of cyclobutanes toward thermal fragmentation. Early examples of the synthetic applications of the olefin metathesis reaction were few and scattered. For example, cyclooctene (I) was shown to macrocyclize catalytically to CIS-cyclohexadeca-l,9-diene (11) (1, 13). In another report (14), perhaps the first stepwise metathesis, formation of Czz monocyclic system (IV) was reported from cyclooctene(1)and chloranil via the his-photoadduct (111). A truly remarkable case of
The second report (18) concerned the interconversions of naturally occuring sesquiterpene dihydroisahelin (X) and its photoisomer dihydrophotoisahelin (XI). The thermal transformation (XI) (X) clearly provided a hint toward development of a metathetical route to medium-ring sesquiterpenes and was almost simultaneously picked up and exploited by several groups (19-22). The generalized version of the different hut conceptually identical approaches shown here renders available 1,5-cyclodecadienes (XII) and/or 1,2-divinylcyclohexanes (XIII) from two functionalized olefins and provides a simple, versatile entry to biologically important germacranolide and elemanolide group of sesquiterpenoids. I t is
-
zo--::. (1)
\ (11)
(XIII)
macrocyclic synthesis is the preparation of catenanes (interlocked rings, VII) by Wolvosky (15) and Wasserman (16) through an intramolecular metathesis of a cyclic "strip" (V) twisted (VI) by 360'. Formation of catenane by metathesis of cyclododecene on tungsten-aluminium catalyst was established conclusively by these groups.
However, evolution of the stepwise metathetical processes into a planned and synthetically useful approach could he traced to two complementary reports in the early 70's. The first was the preparatively significant account by Blwmfield (17) that ethylene as well as other simple cycloalkenes could he potent and efficacious components in the 2 position i n a variety of photocycloadditions and further demonstration that substituted hicvclo (2.2.0) hexane (VIII). . . obtained from dimethyl cycl~~huie~~e-l,2-~licnrl,~~xyla1~ and erhylrne, filrnished
