Propargylation and allenylation of aldehydes

Water was supposed to limit rearrangements between allenyltributylstannane and dibutylstannyl dichloride while these reagents were allowed to react with aldehydes. Nevertheless, complete a-allenic stereoconvergence was not observed. Homopropargylic alcohols could be obtained as well, especially with formaldehyde or a,p-unsaturated aldehydes (Boaretto et al., 1985b). 

On the other hand, zinc-mediated coupling of aldehydes to propargyl bromides in the Luche conditions gave the corresponding homopropargylic alcohols in moderate to high yields together with small amounts of a-allenic alcohols (Yavari and Riazi-Kermani, 1995). 

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Diethylzinc catalyses allenylation of aldehydes and ketones by an allenyl boronate, via a site-selective B/Zn exchange a balance of allenyl and propargyl alcohols are produced. A mild enantioselective addition of vinylzinc reagents (derived from vinyl iodides and diethylzinc) has been reported, with wide tolerance of functional groups. 

Closely related to both allyl carbenoids and the allenyl carbenoids discussed above, propargyl carbenoids 101 are readily generated in situ and insert into zirconacycles to afford species 102 (Scheme 3.27), which are closely related to species 84 derived from allenyl carbenoids [65], Protonation affords a mixture of allene and alkyne products, but the Lewis acid assisted addition of aldehydes is regioselective and affords the homopropargylic alcohol products 103 in high yield. Bicydic zirconacyclopentenes react similarly, but there is little diastereocontrol from the ring junction to the newly formed stereocenters. The r 3-propargyl complexes derived from saturated zirconacycles are inert towards aldehyde addition. 

Propargylic ethers undergo directed lithiation and subsequent transmetallation to afford oxygenated allenyl titanium reagents. Subsequent addition of aldehydes gives rise to various homopropargylic alcohol adducts as mixtures favoring the anti dia-stereomers (Tables 9.18 and 9.19) [29, 30]... 

A related method of preparation involves the oxidative addition of a tin(II) salt to propargylic iodides, which yield mixtures of allenyl- and propargyltin halides on treatment with SnCl2 in DMF-DMI (l,3-dimethylimidazol-2-one) (Eq. 9.75) [68], These intermediates react in situ with aldehydes to afford mixtures of propargylic and allenic carbinols via a cyclic SE2 process (Eqs. 9.76 and 9.77). As explained in the Introduction, the ratio of these two products reflects the relative transition-state energies of the addition reactions. 

A third route to allenyltin halides involves transmetallation of isolable allenyltri-butyltin compounds, as exemplified by the reaction of allenyltributyltin with Bu2SnCl2 [68]. The resulting mixture of allenyl- and propargyldibutyltin chlorides reacts with various aldehydes to afford mixtures of propargyl- and allenylcarbinols (Eqs. 9.78 and 9.79). The yields of these additions are uniformly high, but the selectivity depends on the nature of the aldehyde substituent. The transmetallation route to allenyltin and -indium halides will be discussed in more detail in a later section. 

Substituted prop-2-ynyl mesylates cause propargylation of aldehydes with Snl2, BU4NI, and Nal in DMI to furnish 2-substituted but-3-yn-l-ols, while 3-substituted prop-2-ynyl mesylates promote allenylation under the same conditions to produce 2-substituted buta-2,3-dien-l-ols (Equation (57)). 

Propargylic halides are converted to allenyl and propargylic tin halides upon exposure to SnCl2 in a mixture of A(,A(-dimethylformamide (DMF) and l,3-dimethyl-2-imidazo-lidinone (DMI) [87]. Subsequent addition of aldehydes leads to homopropargylic and/or allenic carbinols (Table 47). The ratio of the two regioisomeric adducts depends on the nature of and R. Alkyl substitution on the alkyne (R = Me) strongly favors the allenic adduct. On the other hand, the ratio of adducts from the TMS substituted alkyne (R = TMS) is dependent on the aldehyde substituent. 

Homopropargyl and allenyl alcohols. Chiral silanes are formed from propargylic mesylates. Subsequent reaction with aldehydes proceeds in a manner depending on the substituent on the sp-carbon of the mesylates. Starting from nonracemic mesylates the products are obtained with excellent ee. 

The catalytic asymmetric propargylation [108] and allenylation [109] of achiral aldehydes has been performed with high levels of enantioselection. The asymmetric propargylation promoted by the chiral Lewis acid derived from bind and Ti(0/-FT)4 are representative. Between 50 and 100 mol% of titanium is required for these reactions to go to completion (Scheme 10-70). The reaction of benzalde-hyde with allenyltributylstannane 170 and the chiral promoter produced the homo-propargylic alcohol 171 in >99% ee and 48% yield (7% of the undesired allenyl alcohol was also obtained). 

Related Sc(OTf)3-catalyzed allylation of aldehydes with allyl-tributyltin in nitromethane, allylation of aldehydes with allyl-germanes, allylation of acylsilanes, and intramolecular allenylation of propargyl silanes have also been reported. The allylation of aldehydes with tetraallyltin proceeds smoothly in micellar systems without using any organic solvents. Novel allylation of aldehydes with alkeneylepoxides is catalyzed by Sc(OTf)3 to produce 5-hydroxy-a, 8-unsaturated aldehydes. ... 

Reactions of propargyl trichlorosilane (21.90) with aromatic, heteroaromatic, and cinnamyl-type aldehydes (21.4), promoted by DMF, have been shown to occur in analogy to the allylation, producing allenyl alcohols 21.91 with >99 1 selectivity (Scheme 21.12). Similarly, allenyl trichlorosilane (21.92)... 

The first report on the conceptually new asymmetric catalysis described that both a stoichiometric amount of SiCU and a catalytic amount of chiral phosphoramide (107) promote highly enantioselective allylation and propargylation of aromatic aldehydes with allyl- and allenyl-tributylstannane, respectively [41], The allylation does not proceed without (107). In the proposed mechanism, SiCU, a weak achiral Lewis acid, accepts the Lewis base (107) to form a strong chiral Lewis acid by polarization of the Si-Cl bonds. The active Lewis acid promotes the asymmetric reaction to give trichlorosilylated adducts with regeneration of (107) (Scheme 9.74). 

In an innovative expansion of the method to include aldehyde propargyla-tion, Marshall has documented the synthesis and use of chiral allenyl tin (169) [104, 111], zinc (174) [112], and indium (175) [113] reagents (Scheme 5.29) [106]. The allenyl zinc and indium species are believed to be formed in situ from chiral propargyl mesylates 172. Oxidative addition of Pd to... 

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. 

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