Lithium-sparteine complexes

The lithium-(-)-sparteine complex, generated by deprotonation of 1-methylindene, does not lose its configuration in diethyl ether solution even at room temperature80 presumably, the observed major diastcreonier is the thermodynamically determined product. Substitution with carbonyl compounds leads to 1-substituted (fl)-l-methyl-l//-indenes with >95% ee in high yields81. 

Enantiomerically and diastereomerically enriched lithium-(-)-sparteine complexes of primary 2-alkenylcarbamates, which are configurationally stable as solids (Section 1.3.3.3.1.2.), are transmetalated stereospecifcally by tetraisopropoxytitanium. The resulting titanates are stable in solution and give rise to homoaldol adducts with enantiomeric purities up to 94 % ee107,107a. 

To a suspension of lithium-(-)-sparteine complex, prepared from 4.0 mmol of ( )-2-butenyl diisopropylcarbamate (Section 1.3.3.3.1.2.), at —78 °C are added rapidly 8.0 mL (28 mmol) of tetraisopropoxytitani-um with intensive magnetic stirring. After 5 min, 980 mg (10 mmol) of 3-methyl-2-methylenebutanal are added and stirring is continued below — 70 °C for 3 h. The mixture is allowed to warm to r.t. and poured into 20 mL of 2N hydrochloric acid and 20 mL of diethyl ether. The aqueous layer is extracted with three 20-mL portions of diethyl ether, washed with sat. aq NaHCO, and dried over Na2S04. Chromatography on 50 g silica gel (diethyl ether/pentane) affords a colorless oil yield 840 mg (78%) 90% ee [a]n° —0.8 (c = 4.4, CH2C12). 

An interesting stereochemical situation was found for the lithium-)—)-sparteine complex derived from o-ethyl-A,A-diisopropylcarboxamide 267 (equation 65) . Control experiments, involving lithiodestannylation experiments and the Hoffmann test, led to the conclusion that 268/ep/-268 are configurationally unstable at —78 °C and the e.r. in 269 is determined by a dynamic kinetic resolution of the rapidly interconverting intermediates . It is noteworthy that the configuration is inverted by using tosylates . 

The lithium-(—)-sparteine complexes, derived from primary 2-alkenyl carbamates, are usually configurationally labile even at —78 °C. During the investigation of the (ii)-crotyl carbamate 301, the (—)-sparteine complex (5 )-302 crystallized in a dynamic thermodynamic resolution process (equation 76) and stereospecific substitutions could be performed with the slurry An incorrect assignment of the configuration of the lithium inter-... 

The lithium-titanium exchange in the allyllithium-sparteine complexes 317 by tetraisopropoxytitanium (TIPT) or chloro-triisopropoxytitanium, resulting in titanates 318, proceeds with strict stereoinversion (equation 84). We assume that—contrary to the lithium-TMEDA complexes—the lithium-(—)-sparteine complexes are weaker Lewis acids and are no longer capable of binding the TIPT in the transition state of the exchange reaction. 

The titanium compounds, derived from the configurationally stable lithium-(—)-sparteine complexes 349a,b prepared from primary allyl carbamates, undergo lithium-titanium exchange with chlorotriisopropoxytitanium to form the allyltitanates... 

Lithium-metal exchange in the lithium-)—)-sparteine complexes 399 or 402, respectively, by diethylaluminium chloride or triisopropoxytitanium chloride proceeds with inversion providing useful reagents for enantioselective homoaldol reactions... 

The X-ray crystal structure of A -Boc-A -/7-methoxyphenyl-3-phenylallyI-lithium-(-)-sparteine complex has been reported [184], This structure differs from the previous structure in that the lithium is associated in an -fashion. The lithium-(-)-sparteine complex resides on the Re face of the ally unit. Stannylation of the lithium complex was established to occur with inversion of configuration. 

A double transmetallation sequence from the lithium-sparteine complex to zinc to mixed zinc-copper species is illustrated in the synthesis of propargylic alcohol 45 (eq 59). 

As far as investigated77, most reactions of the allyllithium-sparteine complexes with electrophiles proceed antarafacially, either as SE2 or anti-SE2 reactions. As a working hypothesis it is assumed that the bulky ligand obliterates the Lewis acid properties of the lithium cation. 

The problem can be solved by the transformation of the lithium carbanions into the more reactive trichlorotitanium intermediates via the stannanes. Finally, the (- )-sparteine complex of (5)-( )-l-methyl-2-butenyl diisopropylcarbamate105 (Section 1.3.3.3.1.2.) is apparently transmetalated by tetraisopropoxytitanium with inversion of configuration, leading to homoaldol products with moderate diastereomeric excess103. 

Early investigations on organometallic (—)-sparteine complexes concern the nucleophilic addition of lithium, magnesium and zinc complexes onto carbonyl compounds, utilization in polymerization and also NMR spectroscopic investigations ... 

The (—)-sparteine-complex of l-(2-pyridyl)-l-(trimethylsilyl)methyllithium is monomeric and shows, according to an X-ray analysis, an almost planar methine group. The lithium cation is placed in a -fashion above the plane of the azaallyl anion moiety. 

Only few types of benzyUithium compounds being configurationally stable in solution at —78°C are known lithium-TMEDA complexes of secondary 0-benzyl Af,Af-dialkyl carbamates, such as 211 or the 2,4,6-triisopropylbenzoate 212 ° , of secondary N-aryl-Af-Boc-benzylamines (213) and the dUithio-(—)-sparteine derivative 214 . ... 

An X-ray crystal structure analysis was obtained from the 3-(trimethylsilyl)-aUyllithium-(—)-sparteine complex (5 )-302b. It reveals the monomeric structure of these aUyllithium compounds and a -coordination of the ally lie anion to the lithium cation. The latter is tetracoordinated and takes advantage of the chelating 0x0 group. The fixation of the lithium at the a-carbon atom is supposed to be the origin of the high regioselectivity of several substitution reactions. 

The classical isomerization of jco-norbornene oxide 82 to nortricyclanol 83 <1964JOC2830> was next examined (Scheme 38) chiral lithium amides or organolithium/(—(-sparteine complexes effected this transformation, with up to 52% ee <1996TA1275>. 

Equilibration of Configurationally Labile Organo-lithium Reagents. The equilibration of diastereomeric pairs of alkyllithium-(—)-sparteine complexes and trapping by achiral electrophiles gives enantioenriched products. Examples are a-(A/,JV-diisopropylcarbamoyloxy)benzyllithium in ether, not in THF, l-phenylethyllithium, and the dilithium salt of A/-methyl-3-phenylpropanoic acid amide (eq 2). ... 

The crucial reagents for the synthesis of the enantioemiched lithium compound (iS)-2 are (-)-sparteine complexes of simple alkyllithium bases. P. Beak and cowokers showed that f-BuLi and i-PrLi complexed by (-)-sparteine could be efficiently used for an asymmetric deprotonation reaction, whereas complexes of the chiral amine and t-BuLi or n-BuLi showed hardly any stereoselectivity or reactivity (Scheme 3) [2]. 

The rationale for the observed configuration (Scheme 3.29), is based on the X-ray structure of another a-carbamoyloxyorganolithium sparteine complex [185]. After deprotonation, the chelated supramolecular complex shown in the lower left is postulated. This structure contains an adamantane-like lithium-diamine chelate, and contains new stereocenters at the lithiated carbon and at lithium itself. Note that epimerization of the lithiated carbon would produce severe van der Waals repulsion between R and the lower piperidine ring, whereas epimerization at lithium produces a similarly unfavorable interaction between the same piperidine ring and the oxazolidine substituents. Thus, the carbamate is tailor-made for sparteine chelation of only one enantiomer of the a-carbamoyloxyorganolithium. These effects may provide thermodynamic stability to the illustrated isomer. To the extent these effects are felt in the transition state, they are also responsible for the stereoselectivity of the deprotonation. 

Both dimethylphenylphosphine-borane (107) and -sulfide (108) are enantio-selectively deprotonated by a lithiumalkyl (—)-sparteine complex as demonstrated by subsequent reaction with electrophiles to give products with e.e. values of 80-87% (Scheme 8). Oxidative coupling of (109) in the presence of copper(II) pivalate gives the (S. S)-isomer (110) as the major product. Asymmetric metalla-tion and silylation of diphenylphosphinyl ferrocene (111) using the chiral lithium amide base derived from di(l-methylbenzyl)amine has been reported to give an... 

The deprotonations are complete within a few hours at -78 °C and afford the lithium car-benoid sparteine complexes (5)-l-(-)-3 with excellent enantioselectivities. [6-12] Whereas sparteine complexes of lithiated secondary allyl and primary alkyl carbamates are configurationally stable below -30 °C, those of primary allyl carbamates such as 4 (-)-3 are not configurationally stable even at -70 °C. It is, however, possible to use these reagents in synthesis, since the preferential crystallization of the S diastereomer in pentane/cyclohexane drives the equilibrium completely to one side. After a low-temperature transmetalation of (5 )-4-(-)-3 with an excess of tetraisopropo-xytitanium, the allylic titanium reagent (Ji)-S is obtained with inversion of configuration. The addition of various aldehydes to (R)-5 furnishes homoaldol adducts of type 6 with... 

Apart from the lithium carbanions, derived from secondary 2-alkenyl carbamates, no further types of configurationally stable a-oxyallyllithium derivatives have been reported in the last 15 years. One must conclude that the five-membered lithium chelate ring plays an important role for the stereochemical integrity. This structure has been nicely demonstrated by the X-ray structure analysis of a sparteine complex [158]. 

---