Alkynyl lithium

Metalated benzene derivatives can also be prepared by the reaction of alkynyl lithium reagents with zirconacyclopentadienes (Eq. 2.55) [39]. 

An exo-type cyclization, proceeding through a cycloalkylidene carbene (49 n = 1, 3, 4), was proposed to explain the formation of enynes (50) and (52) from alkynyl lithium species (48). The proposed carbene (49) could be trapped by addition to cyclohexene and the cycloalkyne intermediate (51) was trapped by Diels-Alder reaction with 1,3-diphenylisobenzofiiran. 

The coordination of the ether oxygen to M1 in 94a decreases the reactivity of the M1-carbon bond towards electrophiles so that E1 is introduced selectively trans to the ether moiety. Reactions of alkynyl lithiums without coordinating substituents lead to stereorandom products. 

Scheme 16). This regioisomer is also obtained in appreciable amounts if bulky lithium organometallies are used. Intramolecular carbolithiations have been reported, such as the cyclization of 5-alkynyl-lithium compounds to furnish the cyclized products in low yields.3... 

This process was first illustrated by Binger and Roster in 1974 (Scheme 17).35 Taking advantage of the readily available alkynyl-borates 21 (obtained by addition of alkynyl lithium or sodium compounds to triorganylboranes),36 the PBs 22a-d were prepared in good to excellent yields. During their investigation of the stereoselectivity of this... 

When (ferf-butylethynyl)aryl-A3-iodanes were mixed with an excess of 2-hthiofuxan or 2-lithiothiophene and subsequently treated with p-TsOH, (2-fuxyl)- or (2-thienyl)aryl-A3-iodanes were obtained [38]. This carbon ligand exchange probably proceeds via selective elimination of the most stable alkynyl-lithium from the tetracoordinated iodate 20 [39]. 

If the cyclisation is not worked up, the product is the alkynyl-lithium that can be added directly to 55 to give the alcohol 54. In the Merck synthesis of efavirenz, this step is used to make a single enantiomer of 64 and this chemistry is discussed in Strategy and Control.16... 

Additionally, acetylene itself is a useful two-carbon building block but is not very convenient to handle as it is an explosive gas. Trimethylsilyl acetylene is a distillable liquid that is a convenient substitute for acetylene in reactions involving the lithium derivative as it has only one acidic proton. The synthesis of this alkynyl ketone is an example. Deprotonation with butyl lithium provides the alkynyl lithium that reacted with the alkyl chloride in the presence of iodide as nucleophilic catalyst (see Chapter 17). Removal of the trimethylsilyl group with potassium carbonate in methanol allowed further reaction on the other end of the alkyne. 

The degree of aggregation of organolithium compounds (alkyl-, aryl-, and alkynyl-lithium compounds as well as lithium enolates) in dilute tetrahydrofuran solution at —108 °C has been determined by means of cryoscopic [289] and NMR spectroscopic measurements [290] for a review on the solution structure of Hthium enolates and phenolates, see reference [406]. 

Organocerium reagents are prepared in situ by the reaction of organolithium compounds with anhydrous cerium chloride or ceriiun iodide, as shown in equation (1). A variety of organolithium compounds can be employed, including alkyl-, allyl-, alkenyl- and alkynyl-lithiums, which are all converted to the corresponding cerium reagents. 

Alkynyl lithiums and Grignards were made in this way in Chapter 9. 

Chiral boronic esters react with organolithium reagents to form diorganylalkoxyboranes (borinic esters). Subsequent reaction with the anion of dichloromethyl methyl ether then yields chiral ketones by rearrangement of both of the groups on boron (Scheme 42). No racemization is observed in this sequence and alkyl-, aryl- or alkynyl-lithium reagents can be used. 

Dialkynyltellurides are easily formed by the reaction of alkynyl Grignard reagents or alkynyl lithium reagents with tellurium tetrachloride. The reaction mixtures contain significant amounts of the butadiyne, a typical ligand coupling reaction product. 

Control of S 2 versus S(j2 additions to vinyl epoxides continues to be of interest. The usual group of alkynyl lithium reagents generally provided a mixture of the S 2 and 8 2 products <05EJO3946>. However when lithio-ethoxyacetylene was used, the 8 2 product 68 was the major product (98 2). Changing the metal to aluminum provided a shift to the 8 2 product 69 in a similar 98 2 ratio as a mixture of E and Z-isomers. 

The use of organometallics shows promise in the preparation of 1,5-disubstituted 1,2,3-triazoIes. A preliminary announcement of the use of lotsich complexes followed by two detailed studies illustrates the rather broad range of possible application (Eqs. 21,22). The yields of 2.2-8 bearing an alkynyl group are good to excellent except with R = Me or Ph. The Russian scientists engaged in these studies have reported experiments with alkynyl lithium salts in which only 4-triazeno products are obtained with certain azides (Eq. 23). 

Halogen leaving groups can be used with type (c) nucleophiles [49] including alkynyl lithium derivative [50]. An impressive example is the reaction of (2,6-dimethyl-l-fluorobenzene)Cr(CO)3 (29) with 2-lithio-2-methyl-l,3-dithiane at -78 °C followed by treatment with trifluoroacetic acid at -78 °C [51]. Loss of HF leads to the 1,2,4 tele) substitution product, (30), in 62% yield. 

We have chosen to represent the alkynyl lithium and alkynyl magnesium halides as organometallics and the alkynyl sodium as an ionic salt. Both probably have some covalent character but lithium is less electropositive than sodium so alkynyl lithiums are more covalent and usually used in non-polar solvents while the sodium derivatives are more ionic and usually used in polar solvents. 

The alkynyl-zinc reagent (37), which is readily obtained from the corresponding alkynyl-lithium and zinc chloride, reacts with alkenyl iodides or bromides in the presence of a catalytic amount of [Pd(Ph3P)4] to give the conjugated enyne (38) in... 

Another reaction between alkynes and CO using alkali metals yields a,3-unsaturated acids. Starting from alkynyl lithium, the lithium trial kylalkynyl borates can be prepared, which react with CO yielding the lithium salt of an unsaturated acid. After further treatment with acetjc acid the stereospecific ., p-unsaturated acids are obtained in yields of about 70-80 % [97] (Figure 34). For instance, trihexylbo-rane and hexynyl lithium led to 2-butylnonenoic acid in yields of 83 %. 

The coupling of alkynyl metals with tertiary alkyl halides without the occurrence of elimination or other side-reactions has been achieved with the organo-alanes, which are prepared from the alkynyl-lithium by reaction with anhydrous AlCl3. Thus, reaction of (Bu C3C— )3A1 with 1-bromoadamantane gave (735 96%) two of the three acetylene units are not utilized and can be recovered nearly quantitatively. It appears that starting material savings caimot be made by using alkynyldialkylalanes since elimination processes tend to occur with t-alkyl halides. The reaction mechanism is not clear. 

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