Lithioacetonitrile

Reaction of Lithioacetonitriles 85.1-85.2 and p-Lithioamino-(3-substituted acrylonitriles 85.3-85.10 with 6 A New General Synthesis of Pyridines and their Condensed Variants... 

The same study shows that with the complex of A W-dimethyl-o-toluidine (38), the selectivity depends on time, temperature and the nature of the anion (Table 4 and equation 34).87 Again, equilibration occurs with the tertiary nitrile-stabilized anion, favoring the C-4 substitution product, while lithioacetonitrile favors addition at C-3. The 2-methyl-1,3-dithianyl anion gives precisely the same product mixture at -78 °C and at -30 C there is no evidence for equilibration with this anion. 

Several asymmetric 1,2-additions of various organolithium reagents (methyllithium, n-butyllithium, phenyllithium, lithioacetonitrile, lithium n-propylacetylide, and lithium (g) phenylacetylide) to aldehydes result in decent to excellent ee% (65-98%) when performed in the presence of a chiral lithium amido sulfide [e.g. (14)], 75 The chiral lithium amido sulfides invariably have exhibited higher levels of enantioselectivity compared to the structurally similar chiral lithium amido ethers and the chiral lithium amide without a chelating group. 

The diastereofacial selectivity of the addition of lithioacetonitrile to 2-phenylpro-panol has been studied over a wide range of temperatures, solvents, and bases.256 Eyring plots [In(dr) vs 1 IT], activation parameters, and inversion temperatures have been characterized. In some cases, the differential entropy of activation, AAS, plays an exclusive role in determining anti -selectivity. 

Diastereofacial selectivity in the addition of lithioacetonitrile to 2-phenylpropanal has been found to be temperature and solvent dependent.42 Each solvent studied (g (benzene, toluene, w-hcxanc, cyclohexane, methylcyclohexane, THF, and diethyl ether) showed a different Eyring plot of In(anti/syn) versus 1 IT with specific differential activation parameters AA H and A AS, and disclosed the presence of inversion temperatures (7]nvs). 

E. Mixed Complexes between Lithioacetonitrile and Chiral Lithium Amides with Ether Groups... 

Mixtures of lithioacetonitrile and chiral lithium amides with both one and two internally coordinating methoxy groups, Li-8, Li-10 and Li-14 respectively, have recently been subject to detailed NMR studies in our laboratory64,65. Mixed dimers are favored... 

The rate constant for the lithium-lithium exchange within the mixed complexes of chiral lithium amides and lithioacetonitrile also differ, depending on the structure. The C-lithiated structures are significantly less fluxional than the /V-lithiated mixed dimers. The activation energy, AG, has been determined for two C-lithiated nitrile complexes in Et20... 

Carbon nucleophiles of type (c) add to the arene ligand and do not rearrange examples include the very reactive anions such as 2-lithio-2-methyl-l,3-dithiane and less sterically encinnbered anions such as lithioacetonitrile and f-butyl lithioacetate. In these cases, the anion adds to an unsubstituted position (mainly ortho or meta to Cl) and does not rearrange. 

Removai of the methoxy group and its substitution by cyanomethyl in the protected estrone derivative shown in the form of the arene chromium tricarbonyl complex in tetrahydrofuran solution, was achieved in 46% yield by treatment at -78 C with lithioacetonitrile (from acetonitrile in tetrahydrofuran containing hexamethylphosphorictriamide and lithium di-isopropylamide at -78°C) followed by stirring for 4 hours at ambient temperature (ref. 104). 

Unsaturated amides and nitriles can be prepared in the same way by use of lithio-N,N-dimethylacetamide and lithioacetonitrile. ... 

Lead fetraacetate-Trifluoroacetic acid, 317 Lead tefrakis(trifluoroacetate), 318 Lemieux-Rudlolf oxidation, 455 Levulinic acid, 354 Levulinic anhydride, 318-319 Levulinic esters, 318-319 Limonene, 535 Lindlar catalyst, 67, 319 Lithioacetonitrile, 34, 636 1-Lithiocyclopropyl bromides, 89... 

Related Reagents. 7V,7V-Diethylaminoacetonitrile 2-(2,6-Dimethylpiperidino)acetonitrile Lithioacetonitrile Methoxy-acetonitrile... 

Insertion into Carbon-Carbon o-Bonds. First examples of this concept were reported with anionic nucleophiles in the context of the addition of a-lithioalkyl and a-lithioarylacetonitriles to arynes. In 1984, Meyers and Pansegrau proposed a cyclization rearrangement mechanism to account for the formation of products 77 in the reaction of a-lithioacetonitriles to 3-oxazolylbenzyne. Initial attack of the nucleophile takes place at C-2 probably due to chelation of the lithium atom from the lithiated nitrile to the oxazoline moiety (Scheme 12.40) [67]. 

If more substituents are desired, the precursor to the cyclobutane can be assembled with more chain extensions with (dichloromethyl)lithium. For example, the (bromomethyl)boronic ester 50 is easily prepared in lots >300 g 26). Alkylation with lithiopropionitrile yielded 51, which was transesterified to astereomeric mixture 52, converted via 53 to in the usual manner, and again treated with (dichloromethyl)lithium to form 55. An analogous series without the methyl substituent was also prepared from lithioacetonitrile. Treatment with LDA led via 56 to cyclobutaiKS 57. This woric was done before the role of magnesium salts in the ring closure was understood, and yields of 57 were consequently not optimized (Scheme 13). 

Scheme 8.22 Reactions of (o-bromoalkyl) boronic esters with lithioacetonitrile.

Cyclobutane synthesis allows introduction of substituents on the cyclobutane ring in various patterns (Scheme 8.24) [55], Allyl bromide with boron trichloride and tri-ethylsilane yields the alkyldichloroborane 103, which is converted into pinacol (3-bro-mopropyl)boronate (104) and on to the cyano derivative 105 by standard methods. Transesterification of 105 and reaction with LiCHClj was used to make 100. However, 105 can be deprotonated and monoalkylated efficiently, and transesterification then yields 106. Transesterification with DICHED and asymmetric insertion of the CHCl group furnishes 107, which cyclizes to 108 or 109 with about the same 20 1 di-astereoselection as seen with the unsubstituted intermediate 100. The pattern of substitution shown by 111 was achieved via reaction of pinacol (bromomethyl)boronate (63) with lithioacetonitrile to form 110, which underwent chain extension and substitution in the usual manner. It was necessary to construct 110 in this way because substitution of a (p-haloalkyl)boronic acid is not possible. With R = H or CH3, substituents included Me, Bu, and OBn [55]. 

Michael Addition. The reaction of a, 8-unsaturated aldehydes andketones with trimethylsilylacetonitrile proceeds with 1,2- and 1,4-regioselectivity, respectively. A synthesis of (+)-sesbanimide highlights the utility of trimethylsilylacetonitrile in a Michael addition to an o(, -unsaturated ester lithiotrimethylacetonitrile gives exclusively the 1,4-addition product, whereas lithioacetonitrile gives mainly the 1,2-addition product. Desilylation of the former adduct results in the product of overall 1,4-addition of lithioacetonitrile. 

Related Reagents. r-Butyl Trimethylsilylacetate N,N-T>i-methyl-2-(trimethylsilyl)acetamide Ethyl Lithio(trimethylsilyl)-acetate Ethyl 2-(Methyldiphenylsilyl)propanoate Ethyl Trimethylsilylacetate Lithioacetonitrile... 

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