Allyl additions simple enantioselectivity

In order to explain the chemistry of allylic metals, the reactions of allylic boron compounds [8,12-14] are covered in detail. The boron chemistry is divided into four parts simple enantioselectivity (addition of CH2=CHCH2-, creating one new stereocenter), simple diastereoselectivity of crotyl additions (relative configuration after CH3CH=CHCH2- addition, where neither reagent is chiral), single asymmetric induction with chiral allyl boron compounds (one and two new stereocenters), and double asymmetric induction (both reactants chiral, one and two new stereocenters). Then follows a brief discussion of other allyl metal systems. 

White and coworkers used trans Addition of bromine and (-)-l-bomeol to 3,4-dihydro-2//-pyran to afford the stereoisomeric bomyl bromotetrahydropyranyl ethers (3) and (4 Scheme 44) which are employed in an enantioselective total synthesis of (-)-monic acid C (Scheme 5).10 A simple synthesis of 4-methylthio-l,2-dithiolane, the photosynthesis inhibitor of the green alga Chara globularis (Scheme 45),83 exploits the observation that allylic sulfides undergo rearrangement on addition of bromine.84 Block and Naganathan employed the trans addition of bromine to 4-thioacetoxycyclopentene as a key... 

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

A new set of stereochemically diverse oxazoline ligands derived from simple amino acids, such as 162, was prepared and employed in the Cr-catalyzed enantioselective addition of allylic halides to aldehydes in up to 95% ee <05OL1837>. 

Interestingly, changing the radical trap from allylstannane to allylsilane increased the enantioselectivity of these allylations from 76% ee to 90% ee (Eq. 6) [10]. The by-product in the allylstannane reactions is tin halide, which is itself a Lewis acid which can promote achiral allylations. In addition, it was observed that a simple change in Lewis acid reversed the sense of stereoinduction. 

The. V-alkylation of ephedrine is a convenient method for obtaining tertiary amines which are useful as catalysts, e.g., for enantioselective addition of zinc alkyls to carbonyl compounds (Section D. 1.3.1.4.), and as molybdenum complexes for enantioselective epoxidation of allylic alcohols (Section D.4.5.2.2.). As the lithium salts, they are used as chiral bases, and in the free form for the enantioselective protonation of enolates (Section D.2.I.). As auxiliaries, such tertiary amines were used for electrophilic amination (Section D.7.I.), and carbanionic reactions, e.g., Michael additions (Sections D. 1.5.2.1. and D.1.5.2.4.). For the introduction of simple jV-substituents (CH3, F.t, I-Pr, Pretc.), reductive amination of the corresponding carbonyl compounds with Raney nickel is the method of choice13. For /V-substituents containing further functional groups, e.g., 6 and 7, direct alkylations of ephedrine and pseudoephedrine have both been applied14,15. 

The paUadium-catalyzed reactions occurred with the simple combination of [Pd(allyl) Cl]j and added phosphine, or with Pd(PPh3) and an acid co-catalyst. The scope of these reactions encompassed the additions of arylamines. As shown in Equation 16.81, reaction of various arylamines with cyclohexadiene occurred with high enantioselectivity using Trost s ligand. This ligand is discussed in more detail in Chapter 20. These reactions, and nickel-catalyzed reactions, occur by nucleophilic attack of amines on ir-allyl intermediates generated by protonation of diene complexes or insertion of dienes into palladium hydrides. 

Recently, Shibasaki and co-workers reported a copperreaction using a chiral diphosphine ligand, DuPHOS, with an added lanthanide salt (118]. This new allylation system provides good levels of enantioselectivity in additions of the simple allylboronate 2 to either aromatic or aliphatic ketones that present a large difference of steric bulk on both sides of the carbonyl (Equation 43). Based on NMR experiments and on the lack of diastereoselectivity in crotylation examples, the suggested mechanism of this allylation involves transmetallation of the boron to an allylcopper species. 

Sigman et al. identified a new set of stereochemically diverse oxazoline ligands derived from simple amino acids that promoted the Cr-catalyzed enantioselective addition of allylic halides to aldehydes in up to 95% ee Ligand diastereomer 28 was found to be the best general catalytic system for these reactions. Furthermore, diastereomer 29 was the ligand of choice for the enantioselective Cr-catalyzed addition of allyl bromide to ketones in up to 93% ee ... 

Hydroboration of terminal alkynes followed by the B/Zn exchange and enantioselective catalytic addition to aldehydes serves as a simple and efficient method for the preparation of chiral nonracemic allylic alcohols. 

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