Lithium species

The optimum conditions for obtaining a high diastereoselectivity are as follows Deprotonation of the sulfoxide must be carried out at 0 C with lithium diisopropyl amide (1 equiv). a lower temperature probably changes the organization of the lithium species and gives lower diastereoselectivity. The condensation reaction is very fast at —78 C, reaction time is usually around 10 minutes3. 

FIGURE 4.40 Mechanistic studies on transformation of lithium species 80. 

Thus, we discovered the first asymmetric nucleophilic addition of acetylides to kehmines. The reaction mechanism was unfortunately not clear during this study but we felt that aggregation of lithium species might play an important role. 

The initiation of the cyclic siloxane monomers with a living polymeric lithium species such as polystyryl lithium leads to block copolymers, as outlined in Scheme 2, were also of interest. These styrenic-siloxane block copolymers were prepared with siloxane contents from 10 to 50 weight percent. 

The zinc complex formed with V,V -diphenylformamidinate is structurally analogous to the basic zinc acetate structure, as [Zn4(/i4-0)L6], and the basic beryllium acetate structure. It is prepared by hydrolysis of zinc bis(diphenylformamidinate).184 Mixed metal zinc lithium species were assembled from dimethyl zinc, t-butyl lithium, V.iV -diphenylbenzamidine and molecular oxygen. The amidinate compounds formed are dependent on the solvent and conditions. Zn2Li2 and... 

Allylic substitution reactions using LPDE have also been reported. The reaction of an allyl alcohol with several nucleophiles proceeds smoothly in a 3.0 M LPDE solution (Scheme 2). 3 Moreover, a highly cationic lithium species has been developed, and a catalytic amount of this species promotes allylic substitution reactions efficiently.14... 

In this chapter, we provide the necessary background concerning the formation of zir-conacycles, then briefly review the insertion of carbon monoxide and isoelectronic isonitriles into organozirconocenes. We then describe in more detail the insertion of a-halo-a-lithium species (R1R2CLiX, carbenoids [7]), which may be viewed as taking place according to a conceptually similar mechanism. 

Murai and coworkers reported on operationally simple aldol reactions with lithium enolates generated from carbonylation of silylmethyl lithium species [57]. Upon 1,2-silicon shift, a-silyl acyllithium species can be stereo-selectively converted to (E) lithium enolates that undergo addition to aldehydes to give /3-hydroxy acylsilanes (Scheme 14). 

The synthetic importance of non-nucleophilic strong bases such as lithium diisopro-pylamide (LDA) is well known but its synthesis involves the use of a transient butyl lithium species. In order to shorten the preparation and make it economically valuable for larger scale experiments an alternate method of synthesis has been developed which also involves a reaction cascade (Scheme 3.14) [92]. The direct reaction of lithium with diisopropylamine does not occur, even with sonication. An electron transfer agent is necessary, and one of the best in this case is isoprene. Styrene is used in the commercial preparation of LDA, but it is inconvenient in that it is transformed to ethylbenzene which is not easily removed. It can also lead to undesired reactions in the presence of some substrates. The advantages of isoprene are essentially that it is a lighter compound (R.M.M. = 68 instead of 104 for styrene) and it is transformed to the less reactive 2-methylbutene, an easily eliminated volatile compound. In the absence of ultrasound, attempts to use this electron carrier proved to be unsatisfactory. In this preparation lithium containing 2 % sodium is necessary, as pure lithium reacts much more slowly. 

An exo-type cyclization, proceeding through a cycloalkylidene carbene (49 n = 1, 3, 4), was proposed to explain the formation of enynes (50) and (52) from alkynyl lithium species (48). The proposed carbene (49) could be trapped by addition to cyclohexene and the cycloalkyne intermediate (51) was trapped by Diels-Alder reaction with 1,3-diphenylisobenzofiiran. 

Geurink and Klumpp measured the protodelithiation enthalpies of 3-lithiopropyl methyl ether, 3-lithiobutyl methyl ether, 5-lithiopentyl methyl ether and 7-5yn-methoxy-2-exo-lithionorbornane in the same study that was discussed in an earlier section for the non-oxygenated compounds n-propyl lithium, n-butyl lithium, 5ec-butyl lithium and 2-norbornyl lithium. The reaction enthalpies for the oxygen-containing lithium species with 5ec-butyl alcohol in benzene were —190 2, —199 4, —190 3 and —199 2 kJmoU, respectively, where all of the lithiated ethers purportedly exist as tetrameric species. 

In the case of medium-size cyclic oxiranes, in the presence of diamine ligands, the decomposition of the oxiranyllithium intermediate can be prevented at low temperature and the lithium species can be trapped by various electrophiles (Scheme 52). The use of (—)-sparteine 112 has led to the corresponding functionalized oxiranes in good ee s. 

The pyrimidine synthesis was therefore changed to the alkynyl ketone route as the appropriate precursors could be formed under much milder conditions. Thus, treatment of the chloro aldehyde 1002 with ethynyl Grignards or lithium species at low temperature, followed by mild oxidation with manganese dioxide, gave the desired chloro alkynyl ketones 1003, which could be successfully converted to the pyrimidine products 1004, by condensation with substituted guanidines, without displacement of the chlorine atom <2003X9001, 2005BMC5346>. 

An anionic equivalent of the Friedel-Crafts cyclization reaction has been developed for the formation of the C /C-5 bond of the 1,2-benzothiazine structure (Equation 35 Table 5) <1997SL1079>. In this reaction, directed metalation of sulfonamide-substituted aromatic systems 233 with an excess of LDA affords aryl lithium species 234 in a regiocontrolled fashion. This intermediate then reacts in situ with a proximal amide to form l,2-benzothiazine-4-one 1,1-dioxides 235. The yields of this transformation appear to be highly dependent upon the substitution pattern in 233. The authors attribute the low yield when = methyl and = H to a-deprotonation of the amide moiety. 

Benzylic deprotonation occurs under normal lithiation conditions when both ortho-positions are occupied. Interestingly, Thomas and co-workers were able to deprotonate a benzylic proton in the presence of an ortho proton (Scheme 8.137). Thus, metalation of 2-(2-methylphenyl)oxazoline 424 produced a benzylic lithium species that reacted with a Cbz-protected leucinal 425 to give a modest yield of the iminolactone diastereomers 426 and 427 together with the expected alcohols 428 and 429. The mixture of 426—429 was efficiently hydrolyzed to give the lactones 430 and 431. 

Di-/m-butyl-4-methylphenyl cyclopropanecarboxylatc (8) can be quantitatively lithiated by treatment with 1 equivalent of le/7-butyllithium at — 78 °C in tetrahydrofuran 64 to give an amine-free, slightly yellow solution of the lithium species 9, which is then attacked by an electrophile to furnish the alkylated product 10 in good yield. Diastereomers were obtained when R1 = CH3 or C6H5. 

The absence of a-alkylated allylic sulfoxides or the corresponding 2,3-sigmatropically rearranged allylic alcohols as well as of y-alkylated vinylic sulfoxides supports the intermediacy of a vinylic rather than an allylic lithium species. 

Thienyliodomium salts (e.g., 28, 29) can be made by direct oxidation of thiophene with iodine in either the +5 or the +3 oxidation states (58JA4279), or by iodination of thienyl-lithium species (77JHC281 80CS(15)135). Such compounds are, however, of limited use only for the synthesis of halogenated thiophenes (Scheme 11). 

Other magnesium allenyl enolates, such as 22, obtained by transmetallation of the lithium species have been used successfully in the preparation of a,-unsaturated acyl silanes (equation 28). ... 

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