Lithium allylic halides

Halogen atoms can be stereoselectively introduced by ring-opening of y-azir-idinyl-a,P-enoates (Scheme 2.39). Treatment of 149 with diethylaminosulfur tri-fluoride (DAST) results in stereospecific ring-opening to yield fluorinated derivative 150 [59]. A related stereoselective conversion of y-aziridinyl-a,P-enoates 151 into allyl halides 152 by use of lithium halide in the presence of Amberlyst 15 was also reported recently [60]. 

Allylstannanes can be prepared by treatment of allyl halides with trialkyl- or triaryltin lithium reagents. Displacement of primary allyl halides tends to be regioselective for formation of the less substituted allylstannane, and takes place with useful retention of double-bond geometry14-16. 

Displacement of secondary allyl halides is satisfactory for the formation of symmetric allylstannanes, e.g., ( )-tributyl(l-mcthyl-2-butcnyl)stannane17, but can give 1,3-rearranged products in other cases, e.g., from 3-chlorobutene and trimethyltin reagents14 lS. Allylic cyclohexenyl chlorides react with triphenyltin lithium with clean inversion and little 1,3-transformation19,20. 

The condensation is usually carried out by adding a solution containing equimolar amounts of the allyl halide and the aldehyde or ketone to a solution of at least two equivalents of chromium-(II) chloride in THF at 0 5°C. Frequently, the less precious component is used in 50-100% excess. Although commercially available anhydrous chromium(II) chloride can be utilized (Method B), its in situ preparation from chromium(III) chloride and lithium aluminum hydride (Method A) is often preferred. The removal of chromium and aluminum hydroxide, which are formed on aqueous workup, can be accomplished by filtration in the presence of a filtration aid. 

C-Alkylations of l,4-dihydro-27/-pyrazino[2,l-A]quinazoline-3,6-diones at positions C-l and CM were studied in detail. Compounds of type 57 could be alkylated diastereoselectively at C-l, owing to the geometry of the piperazine ring, which is locked in a flat boat conformation with the R4 or R1 substituent in a pseudoaxial position to avoid steric interaction with the nearly coplanar C(6)-carbonyl group. Alkylation of 57 (R2 = Me, Bn, R4 = Me) in the presence of lithium hexamethyldisilazide (LHMDS) with benzyl and allyl halides resulted, under kinetic control, in the 1,4-trans-diastereomer 59 as the major product, with retention of the stereocenter at CM (Scheme 5). 

Protected primary allylic amines are prepared from allyl halides and di-r-butyl imidodicarbonate 179 in the presence of lithium iodide, followed by the selective removal of one of the protecting groups by means of trifluoroacetic acid, e.g. equation 66187. 

The first reported radical reaction promoted by tellurium reagent was probably the conversion of allylic halides into the coupled 1,5-dienes by treatment with telluride anions. The reaction, which gives the best results when employing the reagent prepared in situ from elemental tellurium and lithium triethylborohydride, proceeds through the intermediacy of the thermally unstable bis-allylic telluride followed by extrusion of tellurium and coupling of the formed allylic radicals. 

Transmetallation of allyltributyltin with organolithium species has been used for the generation of allyllithium solutions free of the coupling byproducts which often result from reduction of allylic halides with lithium metal. These solutions may then be used directly for the preparation of Gilman reagents and other reactive modifications of the parent allyllithium. 

The conjugate addition reactions probably occur by a mechanism similar to that for substitution on allylic halides. There is probably an initial complex between the cuprate and enone.44 The key intermediate for formation of the new carbon-carbon bond is an adduct formed between the enone and the organocopper reagent. The adduct is formulated as a Cu(III) species which then undergoes reductive elimination. The lithium ion also plays a key role, presumably by Lewis acid coordination at the carbonyl oxygen.45 Solvent... 

The addition of substituted allylic zinc reagents to aldehydes is usually unselective" . Furthermore, the direct zinc insertion to substituted allylic halides is complicated by radical homocoupling reactions. Both of these problems are solved by the fragmentation of homoallylic alcohols. Thus, the ketone 166 reacts with BuLi providing a lithium alcoholate which, after the addition of ZnCl2 and an aldehyde, provides the expected addition product... 

Alkylidene lac tones.1 The alkenylpalladium(II) intermediate obtained in the reaction of lithium alkynoates with PdCl2(CH3CN)2 (12, 50) can be trapped with allyl halides to give (E)-alkylidenelactones. 

Propargyl dianion (QF I ). This anion can be prepared by dilithiation of allene with BuLi in 1 1 ether/hexane. Use of THF (- 50°) or BuLi/TMEDA results in a mixture of propargylide and allenyl anions. The anion couples readily with alkyl and allyl halides to give terminal alkynes. The intermediate lithium acetylide can also react with various electrophiles.3 Example ... 

We had to be careful in chapter 25 when we wanted to add bromoketones 4 to enolates 3 to make the 1,4-dicarbonyl compound 5. We could not use a lithium enolate because it would be too basic. No such difficulties exist in the reaction of enolates with allylic halides such as 2. Any enol(ate) equivalent will do as there are no acidic hydrogens and allylic halides are good electrophiles for the Sn2 reaction. 

Allylic amination of allyl halides can also be achieved using lithium and potassium bis(trimethylsilyl)amides [34] and potassium 1,1,3,3-tetramethyldisilazide [35] as the nucleophiles. It has been found that for the reaction of alkyl-substituted allyl chlorides using lithium bis(trimethylsilyl)amides as the nucleophile the allylic amination proceeds smoothly in a SN2 fashion to give /V,Af-disilylamines in high yields when silver(I) iodide was used as an additive. Other metal complexes such as copper ) iodide and other silver(I) salts can also be used as additives for the reaction. 

The method is less successful with benzylic and allylic halides, and problems of selectivity with these substrates have been overcome in the past via an initial substitution with lithium butyltelluride the organolithium is then formed cleanly from the telluride 135 or 136 (which need not be isolated) by tellurium-lithium exchange.112... 

The complex formed on addition of cuprous iodide to a solution of a lithium dialkylamide in ether or tetrahydrofuran is effective in the reductive coupling of allylic halides to give 1,5-dienes with preservation of stereochemistry. This method has been used5 for the stereospecific synthesis of all-trans-squalene and (E,Z,Z,E) squalene from (E,E)- and (Z,JE)-farnesyl bromides, respectively. In an attempted synthesis of (3S)-squalene-2,3-epoxide, 4-[(4R)-2,2,5,5-tetramethyl-l,3-dioxolan-4-yl]butan-2-one (1) and the phosphonium iodide (2) were prepared.6 Unfortu-... 

The lithium salts of acyclic secondary amines 92 can be conveniently transformed into the corresponding carbamoyllithiums 89 at —78 °C. Under these reaction conditions they react with trialkyltin chlorides to give carbamoyl stannanes 93 (Scheme 24)98. In the case of benzyl and allyl halides, an alkylation can occur affording products 94. However, when trialkylsilyl chlorides were used as electrophiles no carbamoyl silanes could be detected.. V-Alkyl thiocarbamates 95 can be prepared by reaction of the same intermediates 89 with sulfur followed by. S -alkylation at 0°C (Scheme 24)". 

The more reactive ft -carbon atom of ketone a,/ -dianions can be regiospecifically coupled with alkyl halides to give first lithium enolates, which are then trapped by more reactive carbon electrophiles such as allylic halides. The first example shown in Table 8 deals with the sequential /1-alkylation and ce-allylation of a ketone a,/1-dianion1 13. Thus, the dianion underwent regioselective alkylation at the ft carbon with //-pentyl bromide and then allylation with allyl bromide at the a carbon. When an excess of allyl bromide is reacted with the a, ft -dianion, the diallylated product is obtained in a good yield, whereas a threefold excess of pentyl bromide only resulted in the formation of the ft-alkylation product. Similar consecutive alkyl/allyl-type reactions are also possible for ketone a,5-dianions14. 

---