Allyl, substrate controlled addition

Substrate Controlled Addition of Allyl, Alkenyl, and Alkynyl Groups. 255... 

Substrate control This refers to the addition of an achiral enolate (or allyl metal reagent) to a chiral aldehyde (generally bearing a chiral center at the a-position). In this case, diastereoselectivity is determined by transition state preference according to Cram-Felkin-Ahn considerations.2... 

The first example of Pd-catalyzed enantioselective allylation to be reported was the reaction of l-(l -acetoxyethyl)cyclopentene and the sodium salt of methyl benzenesulfonylacetate in the presence of 10 mol % of a DIOP-Pd complex, which led to the condensation product in 46% ee (Scheme 85) (200). This reaction used a racemic starting material, but the enantioselection was not a result of kinetic resolution of the starting material, because the chemical yield was above 80%. However, in certain cases, the selectivity is controlled at the stage of the initial oxidative addition to a Pd(0) species. In a related reaction, a BINAP-Pd(0) complex exhibits excellent enantioselectivity the chiral efficiency is affected by the nature of the leaving group of the allylic derivatives (Scheme 85) (201). It has been suggested that this asymmetric induction is the result of the chiral Pd catalyst choosing between two reactive conformations of the allylic substrate. 

Carbonyl Allylation and Propargylation. Boron complex (8), derived from the bis(tosylamide) compound (3), transmeta-lates allylstannanes to form allylboranes (eq 12). The allylboranes can be combined without isolation with aldehydes at —78°C to afford homoallylic alcohols with high enantioselectivity (eq 13). On the basis of a single reported example, reagent control might be expected to overcome substrate control in additions to aldehydes containing an adjacent asymmetric center. The sulfonamide can be recovered by precipitation with diethyl ether during aqueous workup. Ease of preparation and recovery of the chiral controller makes this method one of the more useful available for allylation reactions. 

The MgBr2-promoted additions are strongly substrate-controlled. As a result it is possible to effect kinetic resolution of racemic y-oxygenated allylic stannanes thereby circumventing the need to employ enantioenriched stannane. The degree of enantio discrimination is somewhat dependent upon the y-oxygen substituent as illustrated by the additions to a threonine-derived aldehyde given in Eq. (46) [66]. 

Metal-activated alkene additions can be classified as stoichiometric or catalytic processes. Stoichiometric processes for THP synthesis typically involve the use of mercury(II) salts and to a lesser extent iodo and seleno reagents. The progress of intramolecular oxymercuration is determined by the stabiUty of the cationic intermediates. Product stereochemistry is under substrate control and usually leads to the thermodynamically more stable THP product. Catalytic variations generally involve palladium complexes [44], but other transition metals are becoming more common (e.g., Pt [45], Ag [46], Sn [47], Ce [48]). The oxidation state of Pd determines the catalyst reactivity. Palladium(O) complexes are nucleophilic and participate in tetrahydropyran synthesis through jt-allyl cation intermediates, whereas Pd(II) complexes possess electrophilic character and progress through a reversible t-complex. 

The preparation of an allyl intermediate from iodooxa-zoline 95 en route to (—)-allosamizoline was achieved though a substrate-controlled diastereoselective Keck allyl addition to give 96 (Scheme 25.45). Allosamizoline is the aglycon of allosamidin, which was isolated from mycelial extracts of Streptomyces sp. No 1731 and inhibits all characterized family 18 chitinases. 

Recently, Bandini and co-workers [175] reported an intramolecular gold(I)-catalyzed asymmetric nucleophihc alkoxylation of allylic alcohols leading to vinyl-substituted six- and seven-membered heterocycles (Scheme 30a). Following this work, Aponick and Biannic [176] developed a synthesis of tetrahydrop5rans in high enantio- or diastereoselectivities (Scheme 30b). The configuration of the allylic alcohol controls efficiently the facial selectivity when the substrates include additional stereocenters. 

In solution, products of central and terminal Br addition to propadiene (la) are formed (Scheme 11.3) [13, 37]. The latter are promoted by high reactant ratios [HBr] [C3H4] and low reaction temperatures. Under conditions of kinetic control, the reaction between diene la and HBr furnishes a 67 33 ratio of allyl bromide 4a versus 2-bromopropene 5a. These investigations also revealed that a-addition of Br is reversible, but the /3-addition is not. The reversible addition to Q has been used to explain the preference for allyl bromide formation from substrate la and H Br at low temperatures, since the Br loss profits from elevated temperatures. 

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