In alkene-directed, nickel-catalyzed coupling reactions of 1,3-enynes with aldehydes and epoxides, the conjugated alkene dramatically enhances reactivity and uniformly directs regioselectivity, independent of the nature of the other alkyne substituent (aryl, alkyl (1 degrees , 2 degrees , 3 degrees )) or the degree of alkene substitution (mono-, di-, tri-, and tetrasubstituted). These observations are best explained by a temporary interaction between the alkene and the transition metal center during the regioselectivity-determining step. The highly substituted 1,3-diene products are useful in organic synthesis and, in conjunction with a Rh-catalyzed, site-selective hydrogenation, afford allylic and homoallylic alcohols that previously could not be prepared in high regioselectivity (or at all) with related Ni-catalyzed alkyne coupling reactions.
Ni-catalyzed reductive coupling of aryl alkynes (1) and enantiomerically enriched α-oxyaldehydes (2) afford differentiated anti-1,2-diols (3) with high diastereoselectivity and regioselectivity, despite the fact that the methoxymethyl (MOM) and para-methoxybenzyl (PMB) protective groups typically favor syn-1,2-diol formation in carbonyl addition reactions of this family of aldehydes.Enantiomerically pure 1,2-diols are important and commonly occuring functional group patterns in natural products such as carbohydrates and polyketides and in chiral ligands used in asymmetric catalysis. Consequently, much effort has been invested in the development of stereoselective methods for 1,2-diol synthesis. A very powerful one for preparing syn-1,2-diols is the Sharpless asymmetric dihydroxylation of trans-disubstituted olefins. 1 However, the diastereomeric anti-1,2-diols are not as easily accessed using this transformation because the corresponding dihydroxylations of cis-disubstituted olefins typically proceed with diminished enantioselectivity. 1cAuxiliary-based, anti-selective glycolate aldol addition reactions have been developed to address this limitation. 2 Nevertheless, these methods are much less common than those for analogous, syn-selective addition, and this area continues to be actively investigated. Recently, MacMillan and List reported catalytic asymmetric aldol reactions that afford the anti-1,2-diol architecture. 3 Aldolases, 4 catalytic antibodies, 5 and a heteropolymetallic catalyst 6 also have been used to favor anti addition in related reactions.A contrasting approach to the synthesis of 1,2-diols involves nucleophilic addition to aldehydes bearing protected hydroxyl groups adjacent to the carbonyl. 7 Cram's rule, after over fifty years, remains a good predictor of the stereochemical outcome of additions to these chiral α-oxyaldehydes (Fig 1) For α-alkoxy groups that have the ability to coordinate (such as MeO-, MOMO-, BnOor PMBO-, among others), the "Cram-chelate" model typically applies, and syn-1,2-diols are favored (Fig 1, A). 8b,9 When larger groups (such as tBuMe 2 SiO-or Ph 3 CO-) are employed, the "dipolar" model is invoked to account for the general preference for anti-1,2-diol products (Fig 1, B). However, due to the greater degree of flexibility in the latter process (σ-bond rotation), nucleophilic additions of this type usually proceed with moderate selectivity and therefore are not always viable means to access anti-1,2-diols.In rare instances, α-oxyaldehydes bearing chelating groups adjacent to the carbonyl afford anti-1,2-diols with >95:5 diastereoselectivity. 10 This unusual preference is particularly interesting from a mechanistic point-of-view because it suggests that even in the presence of highly coordinating groups such as MOMO-or BnO-, the nucleophilic addition occurs instead via the "dipolar" model. This phenomenon may be observed when reagents lacking the ability to chelate are utilized, 10a,10c or when a reagent that imparts complete stereocontrol is employed. 10dWe have...
Alcohols Alcohols P 0110Alkene-Directed, Nickel-Catalyzed Alkyne Coupling Reactions. -The title reactions of 1,3-enynes with aldehydes and epoxides result in regioselective formation of conjugated alkenes. The method can be applied to mono-, di-, tri-, and tetrasubstituted alkynes with aryl and alkyl substituents. Highly substituted 1,3-diene products are used in a Rh-catalyzed, site-selective hydrogenation to afford allylic and homoallylic alcohols that previously could not be prepared in high regioselectivity (or at all) with related Ni-catalyzed alkyne coupling reactions. -(MILLER, K. M.; LUANPHAISARNNONT, T.; MOLINARO, C.; JAMISON*, T. F.; J. Am. Chem.
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