Tertiary alkylzincs

Zinc was effectively activated from zinc chloride using lithium and a catalytic amount (10%) of naphthalene in order to prepare secondary or tertiary alkylzinc bromides 517 (starting from the corresponding aUcyl bromides 516). These reagents react with acyl chlorides or a,/3-unsaturated ketones to give the expected ketones 15 and 518 (Scheme 143). 

They tried Ni catalysts with chelating amine and phosphine ligands in the reaction of phenylzinc bromide with A-benzoyloxymorpholine 2a and observed that in the presence of NiCl2(PPh3)2, n-alkyl, aryl and functionalized arylzinc chlorides can be aminated with A,A-disubstituted O-benzoylhydroxylamines in good yields (Schemes 20 and 21). Attempted amination of secondary and tertiary alkylzinc chlorides failed to yield the expected product. 

SCHIiME 94. Addition of a tertiary alkylzinc reagent to a chiral iminoester... 

Conjugate additions. In the presence of MCjSiCl and BF OEtj, secondary and tertiary alkylzinc bromides add to enones without a copper catalyst. Enhancement of yields and selectivity is also achieved by using MCjSiCI for the conjugate addition of stabilized organolithiums such as (PhSjjCLi. ... 

Ketones. Rieke zinc produced by the reduction of Zn(CN)j with Li naphthalenide reacts with alkyl halides, and the organozinc halides can be used to form ketones on treatment with CuCN and acid chlorides. Secondary and tertiary alkylzinc bromides are readily prepared in this direct manner." a-Chloromethyl ketones have been prepared by this method using chloroacetyl chloride in the coupling reaction. ... 

The phosphine moiety ensures a satisfactory oxidative addition step. Along the same Hnes as the previous system, the electron-deficient alkene moiety accelerates the reductive eUmination step [249]. As shown in the formation of 343, secondary alkylzincs such as 341 are cross-coupled with aryl iodides in good yields, but substantial isomerization occurs with acycUc secondary or tertiary alkylzincs. 

The Formation and Chemistry of Secondary and Tertiary Alkylzinc Halides 45 Table 3.15 Formation and coupling reactions of sec- and f-alkylzinc bromides. 

Table 3.15, entries T-5,0.9 and 0.7 equiv benzoyl chloride, respectively). t-Butyl bromide easily reacted at rt in 1 h to form the zinc reagent. The tertiary alkylzinc bromides (Table 3.15, entries 7-9) couple slowly with benzoyl chloride (0.7 equiv), taking 4-8 h for completion. These results are significant, in that tertiary alkylzinc bromides can be formed readily from active zinc insertion in high yield, which would be difficult or impossible by other methodologies which do not tolerate functionality. 

The Formation and Chemistry of Secondary and Tertiary Alkylzinc Halides 49... 

In summary, methods have been developed which allow for the first time the 1,4-addition of secondary and tertiary alkylzinc bromides to a,p-unsaturated ketones without the need for a copper catalyst or without the presence of cyanide ion. The method is general and will tolerate functional groups. The ability to carry out conjugate additions without copper or cyanide ions represents an economical and exceedingly environmentally friendly approach. Moreover, the reaction temperature need only be -30°C, rather than -78°C as most procedures require. 

Additions of Dialkylzinc Reagents. (lR,2S)-A/-Pyrrolidinyl-norephedrine (1) is an effective catalyst for the enantioselective addition of dialkylzinc reagents to aromatic aldehydes (eq 1). Optimized conditions involve reaction in toluene at 0°C with 10 mol % of the ligand and 2.2 equiv of the dialkylzinc reagent. Normal work-up after 20 h affords the product from addition to the Si face of the aldehyde. Product yields for a variety of alkylzinc reagents (1° and 2°) and an array of aromatic aldehydes are normally 80-100% with ee being nearly 90%. While similar results can be obtained for pyrazole-4-carbaldehydes, aliphatic aldehydes, and 1,2-phthalic dicarbaldehydes, the optimal ligand structure may involve variation of the amine substitution pattern (aliphatic tertiary amine rather than pyrrolidine structure). 

Alkylzinc halides. The structural relationship of several alkyl bromides with reactivity toward Zn has been determined. With 1 equiv of Zn an aliphatic tertiary bromide can be converted to the alkylzinc bromide while retaining a primary bromide. However, 1-bromoadamantane is less reactive than 1-bromopentane. 

The boron-zinc exchange is an unique way for preparing chiral secondary alkylzinc reagents which are configurationally stable over a wide temperature scale. Coupled with the thermal rearrangement of tertiary organoboranes, a broad range of open-chain and cyclic polyfunctional molecules have been prepared. In addition, several examples of a diastereoselective remote C-H activation have been studied. 

---