Allenyllithium

To a solution of 0.35 mol of allenyllithium in 240 ml of hexane and 200 ml of THF (see Chapter II, Exp. 13) were added 25 g of dry HMPT at -80°C. Subsequently 0.30 mol of l-bromo-3-chloropropane were added in 10 min. The reaction was very exothermic, but could be kept under control by occasional cooling in a bath with liquid nitrogen. After an additional 10 min the cooling bath was removed and the temperature was allowed to rise to -30°C. The solution was then poured into 500 ml of water. The organic layer and three ethereal extracts were dried over magnesium sulfate. The solvents were distilled off as thoroughly as possible at... 

Triraethylsilylation of allenyllithium afforded predominantly HCsCCH2SiMe3, while in the cases of the homologues of allene (R = CH3 or primary alkyl) 10-20% contamination by RCsCCHjSiMe3, probably formed by trimethylsilylation of RC(Li )=C=CH2, was present. 

The Li compound 588 formed by the ort/io-lithiation of A. A -dimethylaniline reacts with vinyl bromide to give the styrene derivative 589(433]. The 2-phe-nylindole 591 is formed by the coupling of l-methyl-2-indolylmagnesium formed in situ from the indolyllithium 590 and MgBr2, with iodobenzene using dppb[434]. 2-Furyl- and 2-thienyllithium in the presence of MgBr2 react with alkenyl halides[435]. The arylallenes 592 and 1,2,4-alkatrienes are prepared by the coupling reaction of the allenyllithium with aryl or alkenyl halides[436]. 

Besides protonation, a variety of other electrophiles have been employed for the trapping of allenyllithium intermediates 105, e.g. aldehydes and ketones, oxiranes and carbon dioxide [69]. Scheme 2.38 shows a selection of functionalized allenes obtained by this method. 

A more recent application of this chemistry was reported by Oestreich and Hoppe [74] and involved the enantioselective deprotonation of the enyne carbamate ester 125 with sec-butyllithium in the presence of (-)-sparteine (Scheme 2.41). Removal of the pro-S hydrogen atom led to the corresponding organolithium intermediate, which then underwent a highly enantioselective intramolecular 1,4-addition to the enyne. Protonation of the resulting allenyllithium species 126 provided a 70 30 mixture of the two diastereomeric allenes 127. 

The alkynyl epoxide 73 undergoes a copper-catalyzed reductive metallation by wBuLi [81, 83]. The resultant allenyllithium compound 74 is a versatile intermediate and reacts with various electrophiles (Scheme 3.37). 

In another route to (specifically deuterated) 115, the 3-deuteriopropargyl alcohol 119 was converted to the bromoallene 120 first, which, on butyllithium treatment in diethyl ether, provided the allenyllithium intermediate 121 (Scheme 5.16) [45],... 

Gasking and Whitham described the one-pot preparation of 1-silylated 3,3-di-methyl-substituted allenyl sulfides 307 (Scheme 8.82) [170]. Treatment of alkyne 305 with lithium thiolate generates allenyllithium species 306, which is subsequently silylated by trimethylsilyl chloride. Formation of lithiated intermediate 306 is based on a procedure developed by Clinet and Julia [171]. 

Allenyllithium reagents are commonly prepared through lithiation of propargylic halides or by deprotonation of alkynes or certain allenes (Eq. 9.1). Lithiated allenes often serve as precursors to stable allenylmetal compounds such as stannanes or silanes. They can also be employed for the in situ synthesis of allenylzinc, -titanium and -boronate compounds, which can be further transformed to substitution products not accessible from their allenyllithio precursors. 

Allenes are deprotonated by organolithium bases to yield allenyllithium intermediates. Subsequent treatment of these intermediates with various reactive carbon electrophiles can follow several pathways. An early study showed that terminal allenes bearing a free CH2 substituent afford mainly the direct SE2 substitution product A upon treatment first with BuLi and then with various unbranched alkyl iodides (Table 9.1) [5], A negligible amount of the SE2 propargylic product C was formed under these conditions Small amounts of regioisomeric allene alkylation products B were presumed to arise from 1,3-dilithioallenes. 

The stereochemistry of the process was examined by analysis of the products resulting from trapping the lithioallene from a chiral allenylcarbamate with Me3SiCl (Eq. 9.11). Sequential lithiation with BuLi followed by addition of Me3SiCl at -78°C afforded a 75 25 mixture of the syn and anti adducts in 70% yield. On the other hand, deprotonation with LDA at -78 °C in the presence of excess Me3SiCl gave rise to the syn adduct as the sole product in 70% yield. It could therefore be surmised that (1) lithiation proceeds with retention of stereochemistry and (2) syn/anti isomerization of the putative allenyllithium intermediate at -78 °C is slower than silyla-tion (Eq. 9.12). 

Table 9.4 Formation of allenyllithium intermediates by a Brook rearrangement sequence.

An allenyllithium intermediate was implicated in the reaction of BuLi with an alkynylated cyclohexene epoxide (Table 9.5) [11], It was found that addition of 2equiv. of BuLi to the alkynyloxirane in the presence of 5mol% CuBr-2PPh3 led, after quenching with H20, not to the expected SN2 butylated allene, but instead to the protonolysis product. Likewise, quenching the reaction with Mel or MeSSMe led to the methylated and thiolated allenes, respectively. Furthermore, the putative lithioallene could be trapped by C02 or PhCHO to yield the expected adducts. 

Allenylcopper reagents can be generated from allenyllithium precursors by treatment with stoichiometric amounts of CuBr (Table 9.6) [12]. These intermediates were not characterized, per se, but subsequent reaction with alkenyl iodides led to allenynes in high yield. Thus it is assumed that the reagents are allenic rather than propargylic. The same intermediates afford 2-alkynylsulfmamides on treatment with N-sulfmylaniline (Table 9.7) [13], Cyclization to the N-phenyldihydroisothiazole S -oxides proceeds in nearly quantitative yield on treatment with base. 

An early synthesis of allenylzinc reagents employed a two-step procedure in which monosubstituted allenes were subjected to lithiation in THF with tBuLi at -90 °C and the resulting allenyllithium intermediates were treated with ZnCl2. The allenylzinc reagents thus generated react in situ with aldehydes to afford mainly anti homopropargyl alcohols (Table 9.46) [98],... 

A complementary approach for cross-couplings with allenes was applied by using metallated allene species instead of allenyl halides, which have already been discussed in Sect. 14.2.1. Since allenyllithium compounds are readily available by deprotonation of allenes with n-butyllithium, successful cross-coupling reactions between lithiated allenes such as 54 or 57 and aryl or vinylic halides allowed convenient routes to aryl- and vinyl-substituted allenes, e.g. 55, 58 and 60 (Scheme 14.15) [30],... 

With the aid of 13C NMR, 6Li NMR and XH HOESY (heteronuclear Overhauser effect spectroscopy) NMR of a-lithiomethoxyallene (106) and l-lithio-l-ethoxy-3-J-butylallene (107) as well as by ab initio model calculations on monomeric and dimeric a-lithiohy-droxyallene, Schleyer and coworkers64 proved that 106 and 107 are dimeric in THF (106 forms a tetramer in diethyl ether) with a nonclassical 1,3-bridged structure. The 13C NMR spectrum of allenyllithium in THF is also in agreement with the allenic-type structure the chemical shift of C2 (196.4 ppm) resembles that of neutral allene (212.6 ppm), rather than C2 of propyne (82.4 ppm). 

In addition, the C3-H coupling constant (from a gated decoupling NMR experiment) of 161.8 Hz in 106 compared with 162 Hz in allenyllithium vs 167.5 Hz in methoxyallene and 168 Hz in allene is also in agreement with an allenic structure. However, neither the C-H coupling constant nor the NMR chemical shifts distinguish between the alternatives that 106 has a nonclassical 1,3-bridged structure 108 (M = Li) or an O-coordinated allenic structure (109). Hence the 6Li, -HOESY NMR technique which can be used to detect close proximities (ca < 3.5 A) between XH and 6Li nuclei was applied. The HOESY spectrum of a-lithiomethoxyallene in THF solution (in which 106 is dimeric) is shown... 

Simple diastereoselectivity comes into play when allenylmetal compounds are added to aldehydes, since adducts such as 1 a/b contain both an axis and a center of asymmetry. Hence, diastereomeric mixtures are produced. When chiral aldehydes are used in such reactions, the diastereoselectivity also depends on the relative rate by which the enantiomers of the racemic allenylmetallic species interconvert, i.e., relative to the rate of addition to the chiral aldehyde. Apart from reactions of allenyllithium and -titanium reagents with aldehydes90-94, few such intermolecular, simple diastereoselective reactions yielding allenes have been reported. 

When butyllithium was added to thioethyl-substituted enyne, a carbolithiation reaction occurs to give the allenyllithium species, which may further react with allylzinc (equation 42). This reaction affords thioalkyl-substituted gem-dimetal66. 

Another option for the preparation of allenyllithium reagents involves the carbolithia-tion of activated conjugated enynes15. Thus, addition of BuLi to the enyne 281 led to an allenyllithium compound 282 (in metallotropic equilibrium with its propargylic counterpart). Subsequent addition of allylzinc bromide generated the allylic 1,1-dimetallic species... 

The presence of heteroatoms, not only for the regio- and stereoselective functionalization of the allylic 1,1-diorganometallic species, and/or silyl substituents was found to exert a dramatic influence on the course of the allylzincation of allenyllithium reagents. Indeed, when 1,2-decadiene (285) was metaflated and treated with allylzinc bromide, the reaction followed a different course and led after hydrolysis to the bistoo-methylenejcyclohexane... 

Add zinc bromide (5.2 mL, 5.2 mmol) dropwise to the allenyllithium at 0°C and then stir the mixture for 30 min at room temperature under nitrogen. 

Other internal dienes are not reactive towards carbolithiation, but enynes are. Although the yields are variable, the products are valuable allenyllithiums such as 13.16... 

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