Allenylzinc chiral

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

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 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). 

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... 

Additions of the chiral allenylzinc reagents to enantiomeric -methyl-/ -OBn aldehyde substrates proceeded with a high degree of reagent control to afford anti,syn or anti,anti adducts (equations 23 and 24). In these additions, the preferred anti orientation of the allenyl methyl and the aldehyde substituents requires the reaction to proceed by the normally less-favored anti Felkin-Anh pathway (equation 25). 

Allenylzinc reagents prepared from chiral propargyUc mesylates 64 have been used to synthesize anti-homopropargylic alcohols 65 (Marshall and Adams 1999)... 

The stereochemical outcome may be rationalized as the result of oxidative addition of mesylate to Pd(0) with inversion of configuration, aUenyl-ethyl exchange with retention of configuration, and addition of aldehyde to the aUenylzinc thus formed via syn addition (a cyclic transition state) (Scheme 46). The result of excellent chirality transfer suggests that both allenylpalladium and allenylzinc are configurationally stable and do not isomer-ize (racemize) under the reaction conditions. The reaction is utilized as the key step for the total synthesis of (+)-discodermolide.t ... 

The addition of a chiral allenyl metal to an aldehyde generating a 2-substituted butynyl structure is named Marshall-Tamaru MT) reaction (Scheme 5-13). An allenyl palladium species is generated via a formal Sn2 substitution of the mesylate, which in turn undergoes a transmetalation with diethylzinc yielding a nucleophilic species (Scheme 5-13). The reaction of the electrophile proceeds via a similar -ester enolate transition state as depicted in Scheme 5-13. Corresponding allenylindium reagents can also be used instead of allenylzinc intermediates. ... 

Use of these chiral allenyl metal reagents for the introduction of a propar-gyl group allows the synthesis of all four diastereomeric permutations of dipropionate subunits. The propargyl unit also provides a convenient handle for further elaboration, as demonstrated in Marshall s synthesis of the cytotoxic polyketide discodermolide (182, Scheme 5.30) [115]. Propargylation of aldehyde 177 with an allenylzinc species derived from mesylate 172 furnishes anti product 178 in 90 10 dr. The addition of allenylstannane 180 to aldehyde 179 affords the syn product 181 in an impressive 97% yield and >95 5 dr. 

Propargylic zinc derivatives react with aldehydes or ketones with variable selectivity affording a mixture of allenic and homopropargylic alcohols [135]. However, under appropriate reaction conditions, high enantioselectivities and diastereo-selectivities can be achieved. Marshall and coworkers have shown that chiral propargylic mesylates such as 188 are converted to allenylzinc reagents 189 through treatment with a Pd(0)-catalyst. Their addition to an aldehyde such as 190... 

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