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A number of metals have been used to effect enyne cycloisomerization via these three pathways,
including Pd, Ru, Fe, Ni, Rh, and Ir. 39 The metallocycle pathway is particularly intriguing since
these intermediates have proven high synthetic utility otherwise. For example, metallocyclic
intermediates formed from enynes have been utilized in processes such as cyclocarbonylation,
[2+2], [4+2], [2+2+2] and [5+2] cycloadditions etc. 40-42
Some of the first examples of enyne cycloisomerization were reported by Trost employing Pd(II)
catalyst. 69 For example, enyne 83 rearranges to 1,4-diene 84 when treated with 5 mol %
(PPh3)2Pd(OAc)2 (Scheme 3.3). 69a When steric bulk is introduced at the terminal allylic position
by a cyclohexyl substituent (85), 1,3-diene 86 is obtained. The former transformation has been
extensively applied by Trost to the total synthesis of several natural products. 70
Scheme 3.3 Pd(II)-catalyzed cycloisomerization of enynes.
E
E
E
E
( ) 8
OMe
OMe
5 mol %
(PPh 3) 2Pd(OAc) 2
C 6D 6, 60 o C, 71%
83 84
5 mol %
(PPh 3) 2Pd(OAc) 2
THF, 66 o C, 64%
E
E
E
E
85 86
More recently, Zhang has successfully performed Rh(I)-catalyzed enyne cycloisomerizations
exclusively affording 1,4-dienes. A cationic Rh(I) complex containing a 1,4-diphosphine ligand
(either dppb or 2,2’-bisdiphenylphosphine-1,1’-dicyclopentane - BICPO 71 ) was shown to
catalyze the cycloisomerization of a variety of enynes 87 leading to 5-membered carbo- and
heterocycles 88 (Scheme 3.4). 72 This method is limited to cis-alkenes, while trans-alkenes
proved unreactive. Nevertheless, Rh(I) catalysts have proven highly advantageous, since most
reactions can be performed at rt and the phosphine ligands can be readily tuned to develop an
enantioselective version of the reaction. This idea was put into practice by Zhang by utilizing
32
( ) 8
OMe
OMe