Stereospecific addition, lithium

The stereochemical aspects of the Michael addition of lithium dithioester enethiolates in the challenging acyclic series have been examined [362]. A stereospecific addition of a c/s-enethiolate to an ( )-enone furnishes the anti isomer (6). 

A [2 + 3] dihydrofuran aimulation methodology was recently developed based on this rearrangement. Divinyloxiranes (142) were generated by the stereospecific addition of the lithium dienolate of ethyl a-bromocrotonate to al hydes, and the subsequent pyrolysis to dihydrofurans (143 Scheme 30) occurred in excellent isolated yields (except for R = Bu", Pr ). ... 

Lithium dialkylamide having bulky alkyl groups, such as isopropyl groups, exhibits unique behavior in polymerization reactions of isoprene and divinylbenzene. It was previously reported by us that lithium dialkylamide underwent a stereospecific addition reaction with butadiene in the presence of an appropriate amount of dialkylamine in cyclohexane as solvent (1, 2). For instance, on reacting with butadiene, lithium diethylamide gave the sole adduct, 1-diethylamino-cis-butene-2, in a 98-997o purity. In the absence of free amine, on the other hand, no reaction took place under the same experimental conditions (50°C... 

A new, stereospecific synthesis of (+)-isoretronecanol, by a transannular route, has been developed by Leonard et al. Dieckmann cyclisation of NN-bis-(y-ethoxycarbonylpropyl)benzylamine gave ethyl l-benzyl-5-oxo-l-azacyclo-octane-4-carboxylate (20), whose perchlorate was shown to possess a bicyclic structure. Hydrogenation of this perchlorate in ethanol, using palladised charcoal catalyst, afforded ethyl ( )-isoretronecanolate perchlorate (22) as sole product, presumably by stereospecific addition of hydrogen at the less hindered face of the intermediate debenzylated immonium ion (21). Reduction of the free base corresponding to (22), by means of lithium aluminium hydride, gave (+ )-isoretronecanol (23), the stereochemical purity of which was shown by g.l.c. analysis to be >98%. 

Honma and Ban (307) have reported a second synthesis of deoxyaspidodispermine (158). Crucial in this scheme is the eosine-sensitized stereospecific addition of oxygen to the diene (716) in quantitative yield. Catalytic hydrogenation of 717 under pressure gave diol 718, from which water was eliminated, after basic hydrolysis of the urethane group, to give the indolenine 719. Lithium aluminum hydride reduction gave the indoline 720 which could be acetylated to deoxyaspidodispermine (158) under mild conditions (307) (Scheme 51). 

Polar Solvents and Polar Additives In polar media, the unique high 1,4-stereospecificity with lithium as counterion that is observed in hydrocarbon media is lost and large amounts of 1,2-polybutadiene and 3,4-polyisoprene enchainments are obtained [3, 156], There is a tendency toward higher 1,4-content with increasing size of the counterion in polar media. The highest 1,2-content... 

The methoxyethoxymethoxy (MEM) group can be used to induce further asymmetry into the chiral vinyl sulphone (10). By co-ordinating with methyl-lithium the MEM group facilitates a stereospecific addition to the double bond in... 

Deuterioboration is one of the most important recent additions to the array of methods for saturating double bonds with deuterium. The easy accessibility of metal deuterides (lithium aluminum deuteride or sodium borodeuteride) facilitates the in situ preparation of deuteriodiborane which reacts with steroidal double bonds with a high degree of site and/or stereospecificity, depending on the location of the double bond. " ... 

A similar stereospecific conjugate addition to epoxysulfone 323 was also observed416. When this reaction of 323 was carried out with methyllithium at — 78 °C dichloromethane-diethyl ether (1 1) in the presence of lithium perchlorate, compounds 324 and 325 were obtained in a ratio of 95 5. On the other hand, in the treatment of 323... 

Potassium or lithium derivatives of ethyl acetate, dimethyl acetamide, acetonitrile, acetophenone, pinacolone and (trimethylsilyl)acetylene are known to undergo conjugate addition to 3-(t-butyldimethylsiloxy)-1 -cyclohexenyl t-butyl sulfone 328. The resulting a-sulfonyl carbanions 329 can be trapped stereospecifically by electrophiles such as water and methyl iodide417. When the nucleophile was an sp3-hybridized primary anion (Nu = CH2Y), the resulting product was mainly 330, while in the reaction with (trimethylsilyl)acetylide anion the main product was 331. 

The stereospecific reduction of a 2-butyne-l, 4-diol derivative and silver( I)-mediated cyclization of the resulting allene were successively applied to a short total synthesis of (+)-furanomycin 165 (Scheme 4.42) [68], Stereoselective addition of lithium acetylide 161 to Garner s aldehyde in the presence of zinc bromide afforded 162 in 77% yield. The hydroxyl group-directed reduction of 162 with LiAlH4 in Et20 produced the allene 163 stereospecifically. Cyclization followed by subsequent functional group manipulations afforded (+)-furanomycin 165. 

The stereospecific substitution produces a sterically less strained product when a more bulky p-nitrophenyl substituent occupies the equatorial position and the less bulky phenylthiyl substituent occupies the axial position. Steric limitations of the nucleophile attack caused by strains in the final product are thus removed. And therefore, ion-radical addition ofp-nitrobenzyl radical to the lithium salts of 5-nitro-l,3-dioxanes proceeds stereospecifically (Zorin et al. 1983 Scheme 6.3). 

The first naturally occurring tricyclo[6.3.0.0 ]undecane to be synthesized was isocomene (757), a colorless oily sesquiterpene hydrocarbon isolated from several plant sources. In 1979, Paquette and Han reported an efficient, stereospecific approach starting with a preformed bicyclic enone, to which the third five-membered ring was appended with proper attention to stereochemistry and position of unsaturation (Scheme LXXX) The pivotal steps are seen to be the stannic chloride-induced cyclization of aldehyde 732 and the conjugate addition of lithium dimethylcuprate to 733 which sets the stereochemistry of the last methyl group. 

The boronic ester product usually has properties similar to the starting material, and can be treated with additional (dihalomethyl)lithium (LiCHX2) to introduce another stereocenter. Several repetitions are generally possible, as exemplified by the synthesis of L-ribose5. Most syntheses are finished by treatment with hydrogen peroxide, which replaces the boronic ester group stereospecifically by a hydroxy group. 

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