Enynes bicyclization-carbonylation

TITANIUM-CATALYZED ENANTIOSELECTIVE ENYNE BICYCLIZATION-CARBONYLATION... 

Since the advent of the stoichiometric Zr-promoted enyne bicyclization-carbonylation [19,20], development of its catalytic and enantioselecti ve version has been an attractive but elusive target. Although its catalytic but racemic version has recently been developed in the form of Zr-cataly zed cyclic carboalumination [39], there does not appear to be any successful report on Zr-catalyzed enantioselective enyne bicyclization-carbonylation, the closest process being that discussed in... 

TABLE 4.7. Ti-Catalyzed Enantioselective Enyne Bicyclization-Carbonylation... 

The enyne bicyclization-carbonylation tandem reaction is of great interest to synthesize various organic compounds. Possible mechanisms have been proposed as follows (Scheme 27). 

Prior to the development of enyne bicyclization reactions promoted by Zr and other Group IV metals, the Co-catalyzed enyne bicyclization-carbonylation reaction (the Pauson-Khand reaction ) was known. This reaction is discussed in Volume 5, Chapter 9.1. In the Pauson-Khand reaction, the overall transformation is the conversion of enynes into bicyclic enones, and the organometallic bicyclic intermediates are usually neither readily available nor isolated. The use of Co2(CO)s, an 18-electron species, necessitates relatively high reaction temperatures. These and other limitations suggested the desirability of developing alternative enyne bicyclization reactions. 

Table 1 Zirconocene-promoted Bicyclization-Carbonylation of Enynes ...

Co complexes, Buchwald reported the Ti-catalyzed carbonylative coupling of enynes-the so-called Pauson-Khand-type reaction [28]-and realized the first such catalytic and enantioselective reaction using a chiral Ti complex [29]. Here, a variety of enynes were transformed into bicyclic cyclopentenones with good to high ee-values however, several steps were required to prepare the chiral Ti catalyst, while the low-valent complex proved to be so unstable that it had to be treated under oxygen-free conditions in a glove box. 

When an enyne is reductively coupled in an intramolecular fashion with Zr or Ti, the metallacyclopentene that is obtained initially may be carbonylated to the corresponding bicyclic cyclopentenone with CO. The reaction proceeds by insertion of CO and reductive elimination. In Ti-promoted cyclization, in fact, under certain conditions the Ti(II) fragment produced by reductive elimination can promote reductive coupling of another enyne, providing a basis for a variant of this reaction that is catalytic in Ti. 

Several reports have dealt with the reductive cyclization of enynes where the alkyne component undergoes addition to an adjacent carbonyl group. Typical of this is irradiation of 155, in the presence of the SET sensitizer trie thy lamine, which affords the bicyclic product 156, a piperidone, that was used in a synthesis of z o-oxyskyanthine. Unsaturated aldehydes such as 157 also undergo this photo-electron transfer-induced cyclization to afford a mixture of alcohols 158 (Scheme 6) . Pete and his coworkers have extended their study of this reductive cyclization of unsaturated ketones in a synthesis of hirsutene 159. The reaction involves the irradiation of the ketone 160 at 254 nm in the presence of triethylamine, whereby the tricyclic compound 161 is formed in 58% yield. This is subsequently transformed into hirsutene ... 

Therefore, the aim of the research was to smdy the intermolecular addition of carbonyl compounds to 1,6-enynes bearing a tri-substimted alkene (1-15) catalyzed by gold(l) complexes. This would provide a new methodology for the synthesis of bicyclic compounds of type 1-16. 

Negishi E, Holmes SJ, Tour JM et al (1989) Novel bicyclization of enynes and di5mes promoted by zirconocene derivatives and conversion of zirconabicycles into bicyclic enones via carbonylation. J Am Chem Soc 111 3336-3346... 

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