Allenylzinc

The organozinc reagents 123, which were generated from 1-phenyl-l-alkyne 122 with nBuLi in the presence of 1.5 mol% of HgCl2 followed by addition of 1.5 equiv. of ZnBr2, exists as a tautomeric mixture of an allenylzinc and a propargylzinc species (Scheme 3.62) [103]. 

Palladium-catalyzed cross-coupling reactions of 123 with aryl halides 124 proceeded via the allenylzinc isomers and afforded 1,1-diarylallenes 125 exclusively (Scheme 3.63). 

Allenyllithium reagents are commonly prepared through lithiation of propargylic halides or by deprotonation of alkynes or certain allenes (Eq. 9.1). Lithiated allenes often serve as precursors to stable allenylmetal compounds such as stannanes or silanes. They can also be employed for the in situ synthesis of allenylzinc, -titanium and -boronate compounds, which can be further transformed to substitution products not accessible from their allenyllithio precursors. 

Some synthetically important allenylmetallics, such as allenylzinc and allenylin-dium reagents, are prepared from allenylpalladium intermediates. These reactions are discussed in appropriate sections of this chapter. This section covers the reactions of allenylpalladium compounds without further transmetallation. Allenylpalladium complexes can be prepared from propargylic halides, acetates, carbonates, mesylates, alcohols and certain alkynes [83-87], The allenylpalladium compound prepared from 3-chloro-3-methyl-l-butyne has been isolated and characterized spectroscopically (Eq. 9.106) [83], It was found to couple with organozinc chlorides to produce homologated allenes quantitatively (Eq. 9.107). 

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. 

Scheme 9.29 Possible transition states for additions of the matched (S)/(S) pairing of allenylzinc to lactaldehyde.

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). 

Terminal propargylic mesylates are converted to alkylallenylzinc compounds by reaction with lithiotrialkylzincate reagents (Scheme 9.32) [117]. The latter are formed in situ from dialkylzinc and alkyllithium species. Deuterolysis of the allenylzinc intermediates gave rise to deuterated allenes (Eq. 9.138). 

Scheme 9.32 Synthesis of allenylzinc reagents from propargylic mesylates.

Reaction of the transient zinc intermediates with various electrophiles yielded the acetylenic substitution products and only minor amounts of allenes (Table 9.49). Reactions with aldehydes were non-selective, affording mixtures of stereo- and regioisomeric adducts. However, prior addition of ZnCl2 resulted in the formation of the homopropargylic alcohol adducts with high preference for the anti adduct, as would be expected for an allenylzinc chloride intermediate (Table 9.50). 

Table 9.50 Additions of butyl-allenylzinc reagents to aldehydes.

Thanks are due to Craig Gibeau, Miami University, for providing ChemDraw structures for the allenylzinc and -palladium sections of this chapter. 

Additional examples of palladium-catalyzed cross-couplings, in particular with allenylzinc compounds, can be found elsewhere [11, 15, 36]. A systematic study comparing several chiral palladium phosphine catalysts in the reaction of 4,4-di-methyl-1,2-pentadienylzinc chloride and iodobenzene revealed that an enantiomeric excess of only 25% was obtained from the best catalyst combination PdCl2 and (R,R)-DIOP [15]. The synthetic value of these transformations of donor-substituted allenes as precursors is documented by the preparation of a/l-unsaturatcd carbonyl... 

Wang s synthesis of enyne-allenes by cross-coupling of ene-allenic iodides with alkynes has already been mentioned in Sect. 14.2.1.1 (Scheme 14.12). In a continuation of this work, the same group developed an alternative coupling reaction of allenylzinc chlorides 74 with enyne iodides 75 catalyzed by Pd(PPh3)4, which provided the expected enyne-allenes 76 in high yield and with excellent Z/E selectivity (Scheme 14.17) [38],... 

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

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