Aldehydes reactions with chiral allyl organometallics

Allylic organometallics modified at the metal center by chiral adjuvants add to aldehydes and ketones to provide optically active homoallylic alcohols. This process has been described for reagents containing boron, tin and chromium metal centers. Gore and coworkers have shown that a chromium-mediated addition reaction of allylic bromides to simple aldehydes that uses a complex of lithium N-methyl-norephedrine and chromium(Il) chloride occurs with modest (6-16% ee) enantioselectivity (equation 61, Table 8). 

Aldehyde 50 is an excellent chiral intermediate in reactions with organometallics. Addition at —78 °C of vinylmagnesium bromide to 50, that has been precomplexed with magnesium bromide etherate, affords the chelation-controlled product 51 with remarkably high diaster-eofacial selectivity (155 1). It is imperative that methylene chloride be used as the solvent in order to achieve this level of selectivity. In fact, if commercial vinylmagnesium bromide in THF is to be employed, the THF must be removed and replaced with methylene chloride [13] or else selectivity drops to 40 1. An analogous reaction of 50 with allyl tri- -butylstannane at — 23 °C furnishes chelation-controlled product 52 with 49 1 stereoselectivity. 

The enantioselective addition of allyl organometallics to carbonyls has become one of the workhorses of organic synthesis. Dennis Hall of the University of Alberta reports (J. Am. Chem. Soc. 125 10160, 200.3) the scandium triflate catalysis chiral allylboronic acids become more effective tools. The best of these, the Hoffmann camphor derivative 2, adds to aldehydes under ScfOTOj catalysis with excellent enantiomeric excess. The reaction works equally well for methallyl, and for the E and Z crotyl boronic acids. The crotyl derivatives react with the expected high diastereocontrol. A limitation to the boronate additions is that branched chain aldehydes give low yields. 

To be accurate, the definition should be restricted to asymmetric reactions catalyzed by a combination of l,r-binaphthalene-2,2 -diol (BINOL, 4) and Ti(0 -Pr)4. Nonetheless, this chapter will give some background on non-chiral Lewis acid promoters, and include other asymmetric catalytic systems. We will not discuss the allylations that are promoted by Lewis bases, which are reviewed elsewhere, nor cover the reactions with other electrophiles. Excellent reviews already exist on "Selective Reactions Using Allylic MetaM and Catalytic Enantioselective Addition of Allylic Organometallic Reagents to Aldehydes and Ketones , as well as in the comprehensive monograph "Modern Carbonyl Chemistry. The use of BINOL-based catalysts in other fields of organic synthesis has also been reviewed. ... 

An extension of the asymmetric condensation of organometallics onto aldehydes is the enantioselective silver-promoted allylation reaction of aldehydes with allyltributyltin, which has recently been performed by Shi et al. in the presence of chiral diphenylthiophosphoramide ligands and more efficiently, with binaphthylthiophosphoramide ligands. According to the nature of the ligand substituents, the corresponding allylation products were obtained in enantioselectivities of up to 98% ee, as depicted in Scheme 3.70. 

Amino aldehydes provide useful starting materials for the sequence of Scheme 11.3 because they can easily be prepared from a-amino acids in enantiomerically pure forms and are, therefore, useful chiral building blocks.18 The addition of organometallic allylic reagents (including Zn, used in the reaction described) to such compounds can produce homoallylic alcohols 13 with a high anh-diastereoselectivity. 

Variable enantioselectivities are observed during allylation of aldehydes in the presence of ligand 35. P-Hydroxyaldehydes can be allylated in the unprotected form with a chiral allyltitanium species 36, whereas a-hydroxyaldehydes are readily prepared from 37 by various organometallic reactions. Cinchona alkaloids, being commercially available and inexpensive, are suitable chiral promoters for the indium-mediated allylation, even though they induce only moderate enantioselectivities. Allylation such as that effected by 38 affords products useful for substrate-based alkylation. ... 

Mechanistically related to the Mukaiyama aldol reaction, the carbonyl ene reaction is the reaction between an alkene bearing an allylic hydrogen and a carbonyl compound, to afford homoallylic alcohols. This reaction is potentially 100% atom efficient, and should be a valuable alternative to the addition of organometallic species to carbonyl substrates. However, the carbonyl ene reaction is of limited substrate scope and works generally well in an intermolecular manner only with activated substrates, typically 1,1-disubstituted alkenes and electron-deficient aldehydes (glyoxylate esters, fluoral, a,p-unsaturated aldehydes, etc.), in the presence of Lewis acids. The first use of chiral catalyst for asymmetric carbonyl ene was presented by Mikami et al. in 1989. ° By using a catalytic amount of titanium complexes prepared in situ from a 1 1 ratio of (rPrO)2titaniumX2 (X = Cl or Br) and optically pure BINOL, the homoallylic alcohols 70a,b were obtained in... 

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