Zinc alkyls epoxides

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. 

Once this process is explored with the model system to assess the level of enantioselectivity, we will then prepare alkyl zinc reagent 48 from 44 using standard methods - - and cross couple 48 to aryl bromide 18 using the appropriate chiral catalysts (Scheme 7). Although the acetonide stereocenter in 48 is somewhat remote from the coupling site, the stereocenter may serve to enhance the stereoselectivity of the cross-coupling process because the two possible products are diastereomers, not simply enantiomers. This reaction will produce 49 from (S)-48 and 30 from (R)-48 that can then be converted to epoxides 31 and 32 using standard methods. Epoxide 31 leads to heliannuol D 4 after base-promoted epoxide cyclization and deprotonation. Similarly, epoxide 32 leads to heliannuol A 1 after acid-promoted cyclization. 

Table 6.12 Enantioselective catalytic epoxidation of aryl- and alkyl-substituted a,/l-enones using a (i )-BINOL-zinc catalyst (see Figure 6.13).

An unusual syn addition to epoxides occurs when 1,3-diene monoepoxides are treated with organozinc reagents. Thus, the cyclic vinyl epoxide 72 was converted to the cis-ethyl-cyclohexenol 75 with diethyl zinc in methylene chloride and trifluoroacetic acid. The syn addition is believed to derive from an initial coordination of the oxiranyl oxygen to the organozinc compound, which then delivers the alkyl group to the same face. This transfer is facilitated by a relaxation of the sp3 hybridization brought about by the Lewis acidic zinc center and the allylic character of the incipient carbocation <020L905>. 

Unsymmetrical alkyl phenyl tellurium derivatives were prepared in good yields from phenyl trimethylsilyl tellurium and epoxides, carboxylic acid esters, and linear or cyclic ethers under very mild conditions. In these reactions, which proceed in dichloromethane in the presence of a catalytic amount of zinc iodide, a carbon-oxygen single bond is cleaved. The highly nucleophilic benzenetellurolate binds to the carbon fragment, whereas the trimethylsilyl group becomes linked to the oxygen. 

Synthesis of P-Keto Sulfoxides. Optically active p-keto sulfoxides are very useful building blocks (eq 4) because they can be stereoselectively reduced to afford either diastereomer of the corresponding p-hydroxy sulfoxide under appropriate conditions (Diisobutylaluminum Hydride or Zinc ChloridefDlBALf and thus give access to a wide variety of compounds chiral carbinols by desulfurization with Raney Nickel or LithiumJethyhmme ini the case of allylic alcohols epoxides via cyclization of the derived sulfonium salt butenolides by alkylation of the hydroxy sulfoxide 1,2-diols via a Pummerer rearrangement followed by reduction of the intermediate. ... 

As in the case of the zinc catalysts, active catalysts are formed by reaction of alkyl aluminium compounds with water. It is generally felt that since aluminium compounds are usually fairly strong Lewis acids, the catalysts also are somewhat more acidic in nature. Thus a coordinate cationic mechanism is generally favoured for these polymerizations. In contrast, a more anionic coordinate mechanism is usually suggested for the zinc catalysts. In fact, as will be seen in the discussion of the higher cyclic ethers, some of these catalysts are distinctly able to initiate true cationic polymerizations. However, the catalysts under discussion here as applied to epoxides are clearly considered to be coordinate. 

Reactions with —OH Groups and Epoxides.—The formation of A -l,2-oxaphos-pholen derivatives from propargylic alcohols and phosphorus trichloride has been studied in detail. Intermediate phosphites (24) and allenic phosphonates (25) are described, and the A -l,2-oxaphosphoIen is produced in the final stage, as shown. Improved conditions have been outlined for the preparation of allylic bromides (26) from allylic alcohols and phosphorus tribromide. Related reactions of primary alcohols with the complex of phosphorus trichloride and DMF lead to the chloride (27) 22 addition of zinc bromide to the reaction results in the formation of alkyl bromides, but an attempt to extend this exchange to the preparation of cyanides was not successful. ... 

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