Carboalumination cross-coupling

SCFIEME 5E Synthesis of ft- and -carotenes via an iterative carboalumination-cross-coupling tandem process9... 

Scheme 1.24. Synthesis of alkenylalanes by Zr-catalyzed carboalumination of alkynes followed by Pd- or Ni-catalyzed cross-coupling.

Using ( )-methylalkenylalanes 140, obtained by highly stereo- and regioselective Zr-catalyzed carboalumination of alkynes, the stereochemically defined enynes 141 can also by synthesized by Pd-catalyzed cross-coupling reactions with 1-haloalkynes [Eq. (47)] [68]. 

Utilization of stereodefined alkenylalanes or alkenylzirconium reagents in palladium-catalyzed cross-coupling reactions greatly enhances the versatility of Negishi-type coupling reactions. These organometallics are readily available by hydroalumi-nation, carboalumination, and hydrozirconation of alkynes, respectively. 

B.iv.a. p, P -Substituted Alkenybnetals. Carbometallation reactions of 1-alkynes, most notably carboalumination and carbocupration,t collectively provide a powerful route to the synthesis of /3,j8 -substituted alkenylmetals. The alkenylmetals generated in situ may be used directly for Pd- or Ni-catalyzed cross-coupling with aryl electrophiles (Protocol 1). One prototypical example of the carbometallation-cross-coupling tandem process is shown in Scheme... 

At present, (Z)-/3-substituted alkenylmetals containing other metals are less readily accessible than those mentioned above, even though the Zr-catalyzed carboalumination of ethyne has been shown to produce (Z)-/S-substituted alkenylalanesJ They are generally prepared via metallation-transmetallation of (Z)-/S-substimted hahdes. Despite this drawback, (Z)-/3-substituted alkenylzincs generated by this procedure have been shown to be superior reagents in the subsequent Pd-catalyzed cross-coupling reactiont (Table 11). 

Even today, carotenoids and other natural products represented by 1 and/or 2 are synthesized by using the Wittig and related carbonyl oleflnation reactions that are often not highly stereoselective, thus requiring delicate and tedious separations. Carbometallation reactions of alkynes, " ° especially the Zr-catalyzed carboalumination discovered in 1978,[236].[237] jjj conjunction with Pd-catalyzed cross-coupling have provided a totally different carbometallation-cross-coupling tandem protocol for the synthesis of 1 and 2 (Scheme 59). 

Zr>Catalyzed Asymmetric Carboalumination of Alkenes (ZACA) ZACA-Pd- or Cu-Catalyzed Cross-Coupling Sequential Processes as a General Route to Enantiomerically Enriched Chiral Oiganic Compounds... 

Synthesis of Carotenoids and Retinoids. The Pd-catalyzed cross-coupling reactions of 1 with alkenylmetals containing Al, Zn, and Zr have been shown to be high-yielding and selective. The reaction of 1 with /3,/3-disubstituted alkenylalanes under the conditions of double metal catalysis with Pd and Zn is satisfactory, and the >99% stereospecificity level can be maintained in most cases. Thus, this reaction used in conjunction with the Zr-catalyzed carboalumination of terminal alkynes forms the foundation of a highly stereoselective and... 

The palladium-mediated cross-coupling of organozinc reagents, derived from the asymmetric carboalumination of allyl alcohol, with (iodoethynyl)trimethylsilane (eq 9), has also been reported en route to callystatin... 

D) Palladium catalyzed cross-coupling reactions of organometallics [26] have been developed to a very valuable S30ithetic tool and have received applications in natural product chemistry the vinylalane case being a particular but useful one as such alanes are readily available by zirconium catalyzed carboalumination of acetylenes. More classical organometallics have also been successfully used for such coupling reactions. 

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