Addition of Alkenylzinc Reagents to Aldehydes

At this point, the other ligands were re-examined with t-butylethyne, but no improvement could be made. Clearly, the greater steric bulk of the zinc species resulting from t-butylethyne substantially diminished the stereoselection of the catalyst. In a final attempt to decrease the steric demand of the zinc species, dimethylzinc (3 equiv) was employed as the transmetalation reagent, which should have resulted in formation of the slightly less demanding zinc species (Table 2.1.3.1). 

Alkyne R in aldehyde RCHO Zinc reagent Yield [%] ee(%] 

Gratifyingly, this produced a breakthrough for bulky alkynes. For t-butylethyne 89% ee was achieved with the ligand (Rp,S)-5a, and 88% ee could be obtained for the symmetrical internal alkyne 3 -hexyne. 

The second generation of N,0-[2.2]paracyclophane ketimine ligands (Rp,S)-5b, 6b were investigated for their ability to catalyze the 1,2-addition of alkenylzinc 

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Scheme 3.67 Amino thiol ligand for additions of alkenylzinc reagents to aldehydes.

Addition of alkenylzinc 322 to the aldehyde 321 resulted in a diastere-omer mixture (1 1) of allylic alcohol, which was oxidized to afford ketone 303. Although Terashima s asymmetric aluminum reagent did not give the desired alcohol, the asymmetric borohydride reduction catalyzed by the Corey-Bakshi-Shibata reagent gave a 5 1 mixture of separable diastereomers, in favor of the (17J )-alcohol 323. Finally, protective group manipulation and oxidations led to a seco-acid, which was subjected to Yonemitsu-modified Ya-maguchi macrolactonization to yield the macrocycle (201) (Scheme 68). 

Over the last five years, we have designed, synthesized, and applied new ligands for asymmetric 1,2- and 1,4-addition reactions. Suitable ligands were found for the addition of alkyl-, aryl-, and alkenylzinc reagents to a,(3-unsaturated aldehydes and ketones, a-branched and unbranched aliphatic aldehydes, and imines. Although some substrates such as ketones and other carbonyl compounds have remained a challenge, we believe that this system provides an excellent entry into various classes of chiral intermediates. Application of these synthesized complex molecules is the current pursuit in our laboratories. 

Addition of Cp2Zr(H)Cl to an alkenylzinc hahde affords relatively unstable 1,1-bimetallics of Zn and Zr. Addition of an aldehyde or a ketone is a general way to synthesize ( )-alkenes. Remarkably, the hydrozirconation can be applied to functionahzed alkenylzinc reagents bearing an ester, chloride or cyano functionahty (equation 43). ... 

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