Diastereoselection allenylzinc reagents

Additions of enantioenriched allenylzinc reagents to chiral aldehydes provide intermediates that can be employed in the synthesis of polyketide natural products. Matched and mismatched pairing of reagent and substrate can result in enhanced or diminished diastereoselectivity (Eqs. 9.132 and 9.133) [114]. 

The efficiency and convenience of the chiral allenylzinc reagents are demonstrated in the synthesis of subunits of several natural products. In a total synthesis of bafilomydn Vi, seven of the 13 stereogenic centers were introduced by means of allenylzinc chemistry [112]. Three centers of chirality in the C5-C11 fragment were constructed from the precursor (R)-mesylate and the (R)-aldehyde (Eq. 9.134). The TBS protecting group of the aldehyde is important for high diastereoselectivity. Four of the five stereogenic centers in the Cl 5-C25 subunit were likewise established (Eq. 9.135). 

In the reaction.s of allenylindium and allenylzinc reagents 392 and 391 derived from (R)-3S9, formation of the anti homopropargylic alcohol 393 is favored and highest levels of diastereoselectivity are obtained with branched aldehydes (e.g. cyclohexane carboxaldehyde. Table 11-22). The anti stereochemistry of adducts 393 indicates that these reactions occur through cyclic transitions state in a manner similar to the reactions of the trichloroallenylstannane reagent 226 (see above, Scheme 11-27). 

Finally, the 5jn,ann -dipropionate 402 is best obtained through the reactions of the TBDPS-protected aldehyde 97c with the allenylindium (or allenylzinc) reagent (R)-392, formed in situ from mesylate (5 )-389. The diastereoselectivity of this reaction is best rationalized through the cyclic Felkin transition state 403, where the aldehyde alkyl group and the Me group of the allene adopt an anti relationship in the transition state (Eq. (11.34)). 

Normant and Poisson prepared allenylzinc bromide reagents from TMS acetylenes along the lines of Epsztein and coworkers5, by sequential lithiation with s-BuLi to yield a lithiated species, and subsequent transmetallation with ZnBr2 (equation 35)27,28. Additions to racemic /J-silyloxy aldehydes proceed with low diastereoselectivity to afford mixtures of the anti,anti and anti,syn adducts (Table 17). The latter adducts are formed via an anti Felkin-Anh transition state. Additions to the racemic IV-benzylimine analogs, on the other hand, proceed with nearly complete Felkin-Anh diastereoselectivity to yield the anti,anti amino alcohol adducts (Table 18). 

The same diastereomer is obtained from the ( )-vinyl Grignard reagent [107], and the scope of the reaction is quite broad the use of functionalized vinylmetals as well as the introduction of an alkyl group (different from the methyl group) on the allenylzinc bromide were shown to be possible without altering the diastereoselectivity [107],... 

Enantiomerically pure allenylzinc and indium reagents are readily available through oxidative transmetallation of transient allenylpalladium intermediates derived from sulfonic esters of (/ )- or (5)-3-butyn-2-ol derivatives, such as 250. When these transmetaUations are conducted in the presence of aldehydes, anti homopropargylic alcohol adducts 251 are formed with high diastereoselectivity (Scheme 10.49). The preference for anti over syn adducts can be assigned to an unfavorable eclipsing interaction between the methyl group of allenyl moiety and the... 

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