Issue in Honor of Prof. Eusebio Juaristi ARKIVOC 2005 (vi) 62-87
In order to introduce the remaining 3 carbon atoms of the pironetin side chain, we first promoted a model study involving coupling between tosylate 22 and the corresponding Grignard and cuprate reagents derived from (E)-1-bromo-1-propene (4a) (Schemes 6 and 7).18 Treatment of (E)-1-bromo-1-propene (4a) with Mgo in THF led to the Grignard reagent 4b (Scheme 6). Reaction of (E)-1-bromo-1-propene with tBuLi in THF followed by addition of CuCN provided the expected cuprate 4c (Scheme 6).18 Reaction of tosylate 22 with Grignard reagent 4b gave coupled product 23 in 35% yield. We were not able to get better yields for this reaction. Treatment of tosylate 22 with cuprate 4c led to 23 in 84% yield (Scheme 6).
Mgo, THF MeBr
Me
MgBr
4a 4b
tBuLi, THF Me
CuCN Me
Me
Br
Li
CuCNLi2-78 oC
4a 4c
Me
MgBr (10 equiv.) 4b
CuI, THF OTs
-78 oC to 25 oC 35% Me Me
23 Me
22
Me
CuCNLi2 4c (5 equiv.)
THF, -78oC to25 oC 84%
Scheme 6. Model studies with Grignard and cuprate reagents.
We next moved to the real system (Scheme 7). Treatment of tosylate 5a with Grignard reagent 4b gave bromide 5c in good yields as the sole product, together with starting material. Treatment of tosylate 5a with cuprate 4c (50 equivalents) led to a mixture of primary alcohol 24 (60%) and the desired product 25 in only 15% yield.18 Confirmation that alcohol 24 has been formed in this reaction came from treatment of aldol adduct 19 with LiBH4 and MeOH in THF providing the same alcohol 24 in excellent yields. Bromide 5c also proved to be unreactive under these conditions with both 4b and 4c. In spite of a series of experimental modifications we were not able to improve the yields for the formation of 25.
After examining several different attempts to couple C12 vinyl cuprates, C11 tosylates and bromides, we turned our attention to the use of a Suzuki coupling approach employing an alkyl
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