Allyllithiums substitution

The synthesis of vinylaziridines through reactions between allylic carbenoid reagents and imines (i.e., Darzen-type reactions) was first reported by Mauze in 1980 [13]. Treatment of aldimines or ketimines 16 with gem-chloro(methyl)allyllithium (17) afforded N-substituted vinylaziridines 18 (Scheme 2.6). Similarly, 2,3-trans-N-diphenylphosphinyl-2-vinylaziridines 21 were prepared with good stereoselectivities (trans cis= 10 1 Scheme 2.7) by treatment of a-bromoallyllithium (20) with N-diphenylphosphinyl aldimines 19 in the presence of zinc chloride [14]. 

The addition of a vast number of mainly hetero-substituted allyllithium derivatives to carbonyl compounds has been studied, yet only a few examples proceeding with a preparatively useful level of stereoselectivity have been reported. As many methods were developed before the crucial role of the cation was realized, improvements are possible by simple metal exchange. Some reviews, which collect these reagents, arc cited in Section D.l.3.3.3.1.1. 

Simple 1-hetero-substituted allyllithium derivatives, such as 1-alkoxy-94"96, 1-alkyl-thio-50,97, 1-phenylselenyl-54,98 show insufficient regio- and simple diastereoselectivity in their reaction with aldehydes. The rcgiosclectivity is greatly enhanced in favor of the a-products by in... 

Freparatively useful induced diastereoselectivities have been reported mainly for 1,1-di-substituted allyllithium derivatives which bear carbanion-stabilizing substituents. l-[Methyl-thio-l-(trimethylsilyl)-2-propenyl]lithium106 and the appropriate 1-phenylthio107 derivative, generated from the allylic sulfide with sec-butyllithium, in the reaction with tetrahydropyranyl-protected pregnolone, furnish a single diastereomer. 

In particular 1- or 3-hetero-substituted allylzinc reagents are often prepared in situ by adding anhydrous zinc dichloride or dibromide to the solution of the allyllithium compound. 

Scheme 40 Diastereoselective addition of y-substituted allyllithium and allylzinc reagents to a chiral diimine...

On substitution of allyllithium with methyl groups, the structures are distorted tt complexes becoming more jj -like. The previously described allyllithiums are contact ion pairs (CIP) whose dissociation is too low to permit study of the free carbanion. However, this is not the case for a more delocalized system such as 1,3-diphenylallyl whose lithium salts can exist as solvent separated ion pairs (SSIP) in ethereal solutions for which the organic moiety could be treated essentially as a free carbanion55 Boche and coworkers studied the effect of substitution at C(2) in their 1,3-diphenylallyl lithiums on the rotational barriers... 

Highly substituted 4-methylenetetrahydropyrans can be obtained from the allyl alcohol via its carbamate 20. Reaction of the derived allyllithium with aldehydes affords the (Z)-enolcarbamates 21 which undergo an intramolecular Sakurai cyclisation to the pyran as a single diastereoisomer (Scheme 11) <00TL7225>. 

Hetero-substituted r)3-allyltitanocenes have also been studied. Functionalized q3-allyltita-nium complexes (X = SiMe3, OPh, SPh) have been prepared by transmetallation of Cp2TiCl with the corresponding allyllithiums, and were found to react regiospecifically with propionaldehyde to give functionalized homoallylic alcohols 11 (Scheme 13.14) [25]. 

Deuteration of one end of the allyl moiety in these compounds removes the equivalence of the two positions and in place of the single line for the terminal position, two separate absorptions should appear (W). One, in the normal decoupled spectrum, is a singlet for the hydrogen substituted carbon, and the other a weak quintet for the deuterated end which would be difficult to observe. These two signals would bracket the normal singlet. If a mixture of deuterated and undeuterated allyl compound is used, therefore, two easily observable peaks should appear, one in the normal position, the other shifted. In the spectra of allyllithium and allylsodium the line from the deuterated compound appeared I and 11 Hz upfield respectively, at 0°C, of the normal lines. The potassium compound only showed a somewhat broadened line. At -80°C the separation for allyllithium was 22 Hz. 

In 1998, Kubota, Nakamura and coworkers stndied the addition of substituted (alkoxy)allyllithium and zinc reagents to cyclopropenone acetaP. They found that the regioselectivity of the (alkoxy)allyllithiation is dependent on the substituent, while the diastereoselectivity remains constantly high (>97%). This is supported by their theoretical study (at the B3LYP/6-31G level. Scheme 3) which reveals that a (hydroxy)allyllithium species of 7r-allylmetal nature can react with cyclopropene via two [2 + 2]-type four-centered transition states of similar energies leading to a- and y-adducts. 

The asymmetric lithiation/substitution of Af-Boc-Af-(3-chloropropyl)-2-alkenylamines 395 by w-BuLi/(—)-sparteine (11) provides (5 )-Af-Boc-2-(alken-l-yl)pyrrolidines 397 via the allyllithium-sparteine complexes 396 (equation 106) . Similarly, the piperidine corresponding to 397 was obtained from the Af-(4-chlorobutyl)amine. Intramolecular epoxide openings gave rise to enantioenriched pyrrolidinols. Beak and coworkers conclude from further experiments that an asymmetric deprotonation takes place, but it is followed by a rapid epimerization a kinetic resolution in favour of the observed stereoisomer concludes the cyclization step. 

W-Substituted 2,4-alkadien-l-ols such as 474 add the alkyllithium/(—)-sparteine complex preferentially to the 2-position to form via the alkoxide the corresponding allyllithium intermediates 475 . Protic workup leads to a mixture of ii/Z-alkenols 476 and 477 on catalytic hydrogenation the -branched alcohols 478 are isolated (equation 130). 

Normant coupling reaction between (Z)-y-alkoxyalkenyllithium and trimethylsilyl-substituted allyllithium under the mediation of zinc(II) bromide (Scheme 32)64. 

Haynes et al.3 have examined the effect of HMPT on the reaction of arylthio-allyllithium reagents with cyclopentenonc. In THF alone the reaction leads mainly to 1,2-adducts, derived from both - and /-substitution. However, when the same... 

The formation of diastereoisomerically pure complexes of 90 with (-)-sparteine is also controlled by crystallisation. Treatment of the indene 89 with BuLi and (-)-sparteine in ether gives, on warming, a yellow precipitate which reacts with carbonyl electrophiles to provide the products 91 typically with good regioselectivity and >95% ee.52 An X-ray crystal structure proved the stereochemistry of the intermediate complex to be that shown as 90b, and hence proved the stereochemical course of the substitution (see section 6.1). The complex is readily decomposed by THF, in the presence of which it rearranges to a racemic V allyllithium. 

California Red Scale is a worldwide citrus pest which can be controlled by means of the pheromone 60. Cohen used reductive lithiation to generate versatile allylic nucleophiles applicable to this type of target.6 The allyl sulfide 61 is lithiated by BuLi and reacts with butenyl bromide a to sulfur to yield 63. Reductive lithiation (Li, DBB) of the product yields allyllithium 64. A regioselective reaction of this nucleophile with formaldehyde at the more substituted terminus is ensured by transmetallation to the allyl titanium 65, which gives 66 after treatment with formaldehyde and bromination. 

A second molecule of the lithiated sulfide 62 is then used to introduce the next allylic unit, and reductive lithiation of the product 67 gives allyllithium 68. On this occasion, reaction at the less substituted terminus of the allyl system is required, and this can be achieved by transmetallation (at low temperature, to preserve the cis configuration) to the allylcerium 69. Reaction with formaldehyde followed by acetylation gives the pheromone 60 contaminated by less than 2% of the undesired E isomer. 

Metalation of limoaeae. Crawford el a . report that limonene (1) undergoes selective metalation at C,o on treatment with the 1 1 complex of n-butyllithium and TMEDA to afford the 2-substituted allyllithium species represented by (2). The metalation is carried out by allowing a mixture of 2 eq. of limonene and 1 eq. of the complex... 

Other examples involving functionally substituted vinyl groups are listed in Table 2. (ii) Allyllithiums. Allyllithium is prepared from (CH2=CHCH2)4.Sn and n-BuLi ... 

Table 15. Formation of Functionally Substituted Allyllithiums via Lithiation... 

Furthermore, allenyl phenyl selenides have been prepared by alkylation of 1-lithioallenyl phenyl selenide, itself produc on metallation of phenyl 1-propynyl selenide or of allenyl phenyl selenide - (Scheme 42). 1-Lithioallenyl phenyl selenide has poorer nucleophilic properties than that of a-seleno-allyllithiums, since the reaction of the former with 2-phenyl-1-bromoethane gives predominantly styrene, whereas the latter leads to products of substitution in good yield. ... 

Seyferth showed in 1959 that allyllithium, which is not available from allyl halides because of competing substitution reactions, can be prepared from the reaction of allylstannanes with organolithium reagents (XM = R Li Section 22.1). These reactions involve nucleophilic attack of R upon tin to form a pentacoordinate intermediate. Lewis acids, MX, on the other hand, react by electrophilic attack at the y-position. 

Siloxy-substituted Allyllithium Compounds via [1,2]-Brook Rearrangement... 

As reported by Mauze, the reaction of gem-chloro(methyl)allyllithium (17) with aldimines and ke-timines (18) is an efficient method for the synthesis of 2-vinylaziridines (20 Scheme 3). The aziridine ring is formed by intramolecular Sn2 chloride displacement via the intermediate lithium amide (19). The products are formed as diastereomeric mixtures, as indicated by NMR, and ratios of diastereomers vary depending on the imine substitution. Yields tend to be higher with more accessible linear and branched... 

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