Allenylzinc reagents

An early synthesis of allenylzinc reagents employed a two-step procedure in which monosubstituted allenes were subjected to lithiation in THF with tBuLi at -90 °C and the resulting allenyllithium intermediates were treated with ZnCl2. The allenylzinc reagents thus generated react in situ with aldehydes to afford mainly anti homopropargyl alcohols (Table 9.46) [98],... 

Terminal trimethylsilylacetylenes are deprotonated at the propargylic position by using sBuLi to yield a lithiated species which undergoes transmetallation with ZnBr2 to afford the allenylzinc reagent (Eq. 9.125) [99]. Additions to a-alkoxyalde-hydes are relatively unselective (Table 9.48), whereas additions to a-alkoxy imines are highly anti selective (Eq. 9.126). 

Table 9.48 Additions of non-racemic silylated allenylzinc reagents to racemic silylated mandelic aldehyde.

Scheme 9.27 Kinetic resolution of an allenylzinc reagent using a chiral imine.

A related allenylzinc reagent was prepared by the addition of LDA to a solution of trimethylsilylpropargyl chloride and ZnBr2 in THF at -78°C (Eq. 9.128) [107], Anti propargylic chlorohydrins adducts were obtained when aldehydes were allowed to react with this reagent. Subsequent treatment with DBU gave the alkynyloxiranes (Eq. 9.129). 

Propargylic aziridines were obtained in one step on reaction of this allenylzinc reagent with imines (Eq. 9.130) [108, 109]. 

A mild approach that avoids the use of BuLi has been developed for enantioenriched chiral allenylzinc reagents. Configurationally predictable reagents can be prepared through reaction of a chiral mesylate with Et2Zn in the presence of a palladium catalyst, usually Pd(OAc)2 and PPh3 [110-112], The reagent reacts in situ with an alde-... 

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 factors that control the stereochemical outcome of such rections can be illustrated by additions of enantiomeric allenylzinc reagents to (S)-lactic aldehyde derivatives [114]. The matched S/S pairing proceeds via the cyclic transition state A in which addition to the aldehyde carbonyl assumes the Felkin-Anh orientation with an anti arrangement of the allenyl methyl and aldehyde substituents (Scheme 9.29). The alternative arrangement B is disfavored both by the anti-Felkin-Anh arrangement and eclipsing of the allenylmethyl and aldehyde substituents. 

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). 

The application of this method to trifluoromethyl analogues has been reported [116]. Trifluoromethylpropargylic mesylates undergo highly selective conversion to allenylzinc reagents, which add in situ to aldehydes producing the expected anti homopropargyl alcohols (Eqs. 9.136 and 9.137). 

Scheme 9.32 Synthesis of allenylzinc reagents from propargylic mesylates.

Table 9.50 Additions of butyl-allenylzinc reagents to aldehydes.

Additions of Transient Allenylzinc Reagents to Representative Achiral Aldehydes ... 

The earliest studies on allenylzinc reagents were mainly concerned with the regioselec-tivity of addition reactions to aldehydes and ketones. Moreau and Gaudemar converted... 

When the alcohol adduct from the allenylzinc reagent and diisopropyl ketone was treated with 80 mol% of allenylzinc bromide in HMPA, a mixture containing 12% of diisopropyl ketone and 88% of recovered alcohol was obtained after 7 days at ambient temperatures (equation 1). Thus, it may be deduced that the allenylzinc additions are reversible. Presumably, the propargyl adducts are intrinsically favored, but steric interactions between the R1 and R2 substituents in the propargyl product favors an increased proportion of allenyl adducts in a reversible process (see Table 1). HMPA would expectedly facilitate reversal of the addition by decreasing the ion pairing between the alkoxide anion and ZnBr cation of the adducts. This expectation was subsequently confirmed by a study of solvent effects. 

In their quest for alkynyl-substituted 1,2-diols, Epsztein and workers examined additions of alkoxy allenylzinc reagents to aldehydes (Table 4)5. The reagents were prepared from various propargylic ethers by lithiation with BuLi followed by addition of Znl2. Although exact ratios were not determined, the major propargylic products were surmised to be the anti isomers based on spectral data and comparison with authentic samples. 

The anti stereoisomer was thought to arise from the allenylzinc reagent through a transition state in which the allenyl and aldehyde substituents adopt an anti arrangement (equation 6). The alternative transition state leading to the minor syn adducts would be disfavored by eclipsing interactions between these two substituents. In the proposed transition states, complexation between the zinc halide and the carbonyl oxygen was not considered. 

Zweifel and Hahn found that deprotonation of terminal allenes with -BuLi and subsequent addition of ZnCb leads to terminal allenylzinc reagents, which afford anti adducts upon addition to various aldehydes (Table 5)7. Branching in the aldehyde and allene substituents enhanced the anti syn ratio of adducts, in keeping with the previously proposed cyclic transition state for such additions. 

It was also found that allenylzinc reagents, derived from TMS alkynes by the foregoing lithiation-transmetallation protocol, afford anti adducts in high yield upon treatment with aldehydes (equation 9). 

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