Lithium-base bonds

Better results were obtained for the carbamate of 163 (entry 3) [75, 80). Thus, deprotonation of the carbamate 163 with a lithium base, followed by complexation with copper iodide and treatment with one equivalent of an alkyllithium, provided exclusive y-alkylation. Double bond configuration was only partially maintained, however, giving 164 and 165 in a ratio of 89 11. The formation of both alkene isomers is explained in terms of two competing transition states 167 and 168 (Scheme 6.35). Minimization of allylic strain should to some extent favor transition state 167. Employing the enantiomerically enriched carbamate (R)-163 (82% ee) as the starting material, the proposed syn-attack of the organocopper nucleophile could then be as shown. Thus, after substitution and subsequent hydrogenation, R)-2-phenylpentane (169) was obtained in 64% ee [75]. 

Benzyllithium crystallizes from hexaneAolucnc solution in the presence of l,4-diazabicyclo[2.2.2]oc-tane (DABCO) in infinite polymeric chains. Insoection of the in vidual monomeric units of this structure reveals a unique interaction of the lithium atoms in an Ti -manner with the benzylic carbanion. This bonding is based upon the three relatively short Li—C contacts as indicated in structure (53). The two protons on the benzylic carbon center were located crystallographically one of these lies in the plane of the aromatic ring and the other is significantly out of this plane. A similar Ti -Li—CCC interaction is observed in the diethyl ether solvate of triphenylmethyllithium (54). This latter structure is depicted as (55). 

Alkynyl complexes contain metal-carbon bonds in which the metal is bound to the sp-hybridized carbon at the terminus of a metal-carbon triple bond. The materials properties of these complexes have been investigated extensively. The properties of these complexes include luminescence, optical nonlinearity, electrical conductivity, and liquid crystallinity. These properties derive largely from the extensive overlap of the metal orbitals with the ir-orbitals on the alkynyl ligand. The M-C bonds in alkynyl complexes appear to be considerably stronger than those in methyl, phenyl, or vinyl complexes. Alkynyl complexes are sometimes prepared from acetylide anions generated from terminal alkynes and lithium bases (e.g., method A in Equation 3.42), but the acidity of alkynyl C-H bonds, particularly after coordination of the alkyne to the transition metal, makes it possible to form alkynyl complexes from alkynes and relatively weak bases (e.g., method B in Equation 3.42). Alkynyl copper complexes are easily prepared and often used to make alkynylnickel, -palladium, or -platinum complexes by transmetallation (Equation 3.43). This reaction is a step in the preparation of Ni, Pd, or Pt alkynyl complexes from an alkyne, base, and a catalytic amoimt of Cul (Equation 3.44). This protocol for... 

Another [IJrotaxane R25 via covalent-bond formation based on a crownlike macrocycle has been reported previ-onsly, as shown in Figure 15 P The eqnimolar reaction of 4 with 5 gave bicyclic compound 3 (mixtnre of two isomers). Then 3, without separation of isomers, was used in aminol-ysis with 9-(3-(aminopropyl) aminocarbonyl)-anthracene 2. Treatment of mixed isomers of 3 with 2 in DMF at room temperature gave birth to [IJrotaxane R25 (yield 20%) and a reference compound Ref-R25 (yield 45%). R25 had a three-dimensionally small cavity constructed by the ring and the chain connected with the macrocycle, which could catch only the lithium ion with a drastic enhancement of fluorescence intensity of the R25 solution. 

The metalation reaction, that is, the conversion of a relatively unuseful carbon-hydrogen bond to a synthetically advantageous carbon-metal bond, is one of the most important and widespread chemical transformations practiced today. A key intermediary tool for the preparation of pharmaceuticals, agrochemicals, perfumes/ cosmetics and fine chemicals, amongst other everyday commodities, the metalation reaction has typically been the domain of the highly polar alkali metals, nearly always lithium. Indeed, Collum emphasized this domination in 1993 stating that it would appear that well over 95% of natural products syntheses rely upon lithium based reagents in one form or another [1]. 

Treatment of geminal dihalocyclopropyl compounds with a strong base such as butyl lithium has been for several years the most versatile method for cumulenes. The dihalo compounds are easily obtained by addition of dihalocarbenes to double--bond systems If the dihalocyclopropanes are reacted at low temperatures with alkyllithium, a cyclopropane carbenoid is formed, which in general decomposes above -40 to -50°C to afford the cumulene. Although at present a number of alternative methods are available , the above-mentioned synthesis is the only suitable one for cyclic cumulenes [e.g. 1,2-cyclononadiene and 1,2,3-cyclodecatriene] and substituted non-cyclic cumulenes [e.g. (CH3)2C=C=C=C(CH3)2]. 

When 2-lithio-2-(trimethylsilyl)-l,3-dithiane,9 formed by deprotonation of 9 with an alkyllithium base, is combined with iodide 8, the desired carbon-carbon bond forming reaction takes place smoothly and gives intermediate 7 in 70-80% yield (Scheme 2). Treatment of 7 with lithium diisopropylamide (LDA) results in the formation of a lactam enolate which is subsequently employed in an intermolecular aldol condensation with acetaldehyde (6). The union of intermediates 6 and 7 in this manner provides a 1 1 mixture of diastereomeric trans aldol adducts 16 and 17, epimeric at C-8, in 97 % total yield. Although stereochemical assignments could be made for both aldol isomers, the development of an alternative, more stereoselective route for the synthesis of the desired aldol adduct (16) was pursued. Thus, enolization of /Mactam 7 with LDA, as before, followed by acylation of the lactam enolate carbon atom with A-acetylimidazole, provides intermediate 18 in 82% yield. Alternatively, intermediate 18 could be prepared in 88% yield, through oxidation of the 1 1 mixture of diastereomeric aldol adducts 16 and 17 with trifluoroacetic anhydride (TFAA) in... 

An excellent synthetic method for asymmetric C—C-bond formation which gives consistently high enantioselectivity has been developed using azaenolates based on chiral hydrazones. (S)-or (/ )-2-(methoxymethyl)-1 -pyrrolidinamine (SAMP or RAMP) are chiral hydrazines, easily prepared from proline, which on reaction with various aldehydes and ketones yield optically active hydrazones. After the asymmetric 1,4-addition to a Michael acceptor, the chiral auxiliary is removed by ozonolysis to restore the ketone or aldehyde functionality. The enolates are normally prepared by deprotonation with lithium diisopropylamide. 

Finally, the use of simple valence bond theory has led recently to a significant discovery concerning the nature of metals. Many years ago one of us noticed, based on an analysis of the experimental values of the saturation ferromagnetic moment per atom of the metals of the iron group and their alloys, that for a substance to have metallic properties, 0.72 orbital per atom, the metallic orbital, must be available to permit the unsynchronized resonance that confers metallic properties on a substance.34 38 Using lithium as an example, unsynchronized resonance refers to such structures as follows. 

In the presence of a strong base, the ot carbon of a carboxylic ester can condense with the carbonyl carbon of an aldehyde or ketone to give a P-hydroxy ester, which may or may not be dehydrated to the a,P-unsaturated ester. This reaction is sometimes called the Claisen reaction,an unfortunate usage since that name is more firmly connected to 10-118. In a modem example of how the reaction is used, addition of tert-butyl acetate to LDA in hexane at -78°C gives the lithium salt of ferf-butyl acetate, " (12-21) an enolate anion. Subsequent reaction a ketone provides a simple rapid alternative to the Reformatsky reaction (16-31) as a means of preparing P-hydroxy erf-butyl esters. It is also possible for the a carbon of an aldehyde or ketone to add to the carbonyl carbon of a carboxylic ester, but this is a different reaction (10-119) involving nucleophilic substitution and not addition to a C=0 bond. It can, however, be a side reaction if the aldehyde or ketone has an a hydrogen. 

Another method that has been used to prepare phosphaalkenes is the phos-pha-Peterson reaction, a phosphorus analog of the Peterson olefination [46-49]. In this reaction a lithium silylphosphide is treated with an aldehyde or ketone to yield the phosphaalkene (9). Analogous reactions can be conducted with bis(trimethylsilyl)phosphines (10) and ketones (11) using a catalytic quantity of anhydrous base (i.e., NaOH, KOH) [50]. Generally, the reactions proceed cleanly and in high yield. Sufficiently bulky substituents must be employed to stabilize the P=C bond and prevent rapid dimerization to 1,3-diphosphetaines. 

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