Amide cuprates

A novel asymmetric synthesis of a-amino acids via electrophilic amination has been demonstrated by Zheng and Armstrong and co-workers.94 No +NHBoc was observed when lithium tert-butyl-A-tosyloxycarbamate (LiBTOC) was reacted with zinc and lithium enolates of 48. Transmetallation of the lithium enolate with copper cyanide was necessary to generate a reactive amide cuprate, which then added efficiently to the electrophile. The electrophilic amination of chiral cuprates with LiBTOC provided an expedient approach to a-amino acids with predictable absolute configuration in high enantiomeric purity and good yield (Scheme 24.23). 

The Merck group has applied the electrophilic amination using lithium terf-butyl N-(tosyloxy)carbamate 9a to the chiral amide derived from (lS,2/ )-cw-amino-indanol [10] (Scheme 4). Treatment of 10 with n-Buli in THF at -78 °C gave the lithium enolate which was reacted with CuCN. The resulting amide cuprate was allowed to react with 9a. The authors found that a single diastereomer of a-Boc-protected amino amide 11 was formed. The sense of asymmetric induction observed was consistent with preferential approach of 9a from the least hindered face of the enolate. The removal of the chiral auxiliary with refluxing 6N HC1 afforded a-amino acids 12 in good yields and optical purities. 

The relative stereocontrol of carbons 1, 2 and 6 observed in the above example has been assigned to the intramolecular chelation of the lithium of the intermediate enolate by the carbonyl of the second ester group. Note that lithium amide cuprate reagents also add efficiently to enoates and dienoates163. 

Amide cuprates 0-lactams S Amide cuprates such as [BziSi(CH,),N 2CuLi (1) react with 1,3-dienoates to give with high or exclusive rcgioselectivity the 1,4-adduct l equation 1). I his reaction can be extended to a three-component coupling. Thus reaction... 

Non-ate allylcopper is also useful in the chlorides and epoxides. 1,2-Amino alcohol with amide cuprate reagents. ... 

Oniy diastereomer Yamamoto s asymmetric addition of amide cuprate [6]... 

Scheme 54 shows the synthesis reported by Cox et al. of the pyrazoline compound 198 [98]. The Weinreb amide (e.g., 199) was reacted with a terminal alkyne followed by a reaction of the resulting alkyl ketone (200) with an aryl cuprate to produce the pyrazoline 198. Cox et al. employed the use of microwave technology in this reaction. Kidwai and Misra also employed microwave technology to produce pyrazoline compounds [99]. 

Carbamates also serve as satisfactory starting materials for this methodology (Eq. 9.42) [49]. In this variation, lithiation of the carbamic amide precedes displacement by the cuprate reagent. 

This technique also greatly improves yields of conjugate addition of cuprates to y..[>-unsaturated esters and amides.38 Trimethylsilyl cyanide also accelerates conjugate addition.39... 

Aldehydes and ketones have also been prepared by nucleophilic cleavage of resin-bound O-alkyl hydroxamic acids (Weinreb amides [744]) with lithium aluminum hydride [745] or Grignard reagents (Entries 1 and 2, Table 3.41). Similarly, support-bound thiol esters can be cleaved with Grignard reagents to yield ketones [272], or with reducing agents to yield aldehydes (Entry 3, Table 3.41). Polystyrene-bound sele-nol esters (RCO-Se-Pol) react with alkynyl cuprates to yield alkynyl ketones [746]. 

V,7V-Diethylcarbamoyl trimethylsilane has been prepared by the reaction of bis(trimethylsilyl) sulphide with bis(A,A-diethylcarbamoyl) mercury (Scheme 30)16. Silylation of the carbamoyl cuprate reagent derived from a lithium amide, by addition of copper(I) cyanide and subsequent exposure to carbon monoxide (1 atm), is also effective75,110. Poor to moderate yields of carbamoyl silanes may be isolated by treatment of lithium silylamides with carbon monoxide and methyl iodide, in a reaction sequence involving a nitrogen to carbon silyl shift in an intramolecular silylation (Scheme 31)111. 

Lithium bis(i -methyl-N-phenylcarbamoyl)cuprate, [C6H5N(CH3)CO]2CuLi (l).28 The cuprate is prepared by reaction of CO with lithium N-methylanilide in the presence of 0.5 equiv. of Cul. The complex converts alkyl halides into amides in good yield. The reaction is not useful with aryl halides or benzyl halides. 

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