Oxepines ring-closing metathesis

Ring-closing metathesis has been used effectively to prepare the pyrido[3,2-h oxepine derivative 71 in good yield from the pyridyl diene precursor 70 <06TL6235>. 

The oxepine-fused beta-carboline 73 was synthesized in good yield (71%) from the diene precursor 72 using ring-closing metathesis and Grubbs I catalyst <06TL6895>. 

In the previous section, the cyclopropanation of a glycal to form a bicyclic intermediate was followed by a ring-expansion reaction en route to each oxepine. Presented here are routes that afford oxepines either by ring-closing metathesis (RCM) reactions or by cycloisomerization of terminal alkynes. 

Partially hydrogenated oxepin-4-one system is convenient as a starting material for the synthesis of diverse oxepane-based compounds, such as peptidomimetics. A simple, five-step synthesis of one of the oxepin-4-ones from BOC-D-phenylalanine (Scheme 20) is developed using olefin ring-closing metathesis (RCM), as the final step (BOC = f-butoxycarbonyl) <2003TL5511>. 

Ring closing metathesis was also used to prepare the key oxepine derivative 123 starting from the allofuranose 122 compound 123 then served as a precursor for the ultimate synthesis of the zoaptanol analogue 124 [01TL5749],... 

An alternative to ring-closing metathesis to access seven-membered rings has been described by Ohno et al. <03H(61)65>. Thus, reaction of the bromoallene 4 containing a nucleophilic moiety and Pd(PPh3)4 in the presence of methanol affords the azepine derivative 5 in good yield (76%). Oxepine derivatives can also be made in a similar way using an alcohol as the nucleophilic moiety in the allene. 

A novel quinolone-ring fused oxepine 56 (n = 1), reported by Joseph et al., was accessed by a ring-closing metathesis reaction on the precursor 55, which was made in turn from 53 via 54, and a Claisen rearrangement on the last compound. An aza analogue of 56 (n = 1) was made in a similar direct approach <03SL2089>. 

The ring-closing metathesis approach was used beneficially to prepare isomeric seven-membered oxepine derivatives by Schmidt and Biernat. Thus, with the use of Grubbs first-generation catalyst, the metathesis of 33 afforded oxepine 34, whereas a tandem ring-closing metathesis-isomerization of the same substrate afforded glycal 35 (Scheme 13.9) [22]. 

SCHEME 13.8 Metal-catalyzed ring-closing metathesis reactions to prepare oxepines 30 and 32 [20,21]. 

SCHEME 13.9 Ring-closing metathesis reactions leading to oxepine 34 and 35 [22],... 

Ring-closing olefin metathesis has been extended to vinyl chloride precursors, resulting, for example, in the preparation of the chloro-substituted oxepine derivative 43 from 42 in high yield (88%) <030L2505>. 

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