1 -Lithio-1 - allenes

Far greater (Z)-selectivity is observed in reactions of the anion of lb, in which the (Z)/(E) ratio is 20 1. Moreover, the selectivity of this reaction is almost completely reversed by addition of HMPT. The effect of HMPT is exerted on the carbonyl addition step and not on the subsequent elimination to form the double bond. Corey and Rucker1 suggest that lithiated lb reacts mainly as a lithio allene in THF, but mainly as the propargylic anion in THF-HMPT. 

Allenes can be directly deprotonated using alkyllithiums, and the intermediate lithio allenes can then be alkylated efficiently by primary alkyl bromides or iodides." For example, good yields of homologated allenes can be realized under the conditions specified in Scheme 23 (the brief reaction time appears... 

A truly delightful exploitation of this idea is a synthesis of thieno[2,3- ]thiophene, in which a diyne is lithiated to give a lithio-allene, which reacts with carbon disulhde. ... 

The recent discovery that propadiene can be converted into a lithio compound, which is stable enough at low temperature to allow functionalization, has made it an important starting compound for the synthesis of derivatives. A fortunate circumstance is that allene can be obtained in > 30% yield in an extremely simple... 

Methylene thiirane is obtained by thermolysis of several spirothiirane derivatives which are formally Diels-Alder adducts of methylenethiirane and cyclopentadiene or anthracene <78JA7436). They were prepared via lithio-2-(methylthio)-l,3-oxazolines (c/. Scheme 121). A novel synthesis of the allene episulfide derivatives, 2-isopropylidene-3,3- dimethylthiirane (good yield) or its 5-oxide (poor yield), involves irradiation of 2,2,3,3-tetramethyl-cyclopropanethione or its 5-oxide (81AG293). Substituents on the thiirane ring may be modified to give new thiiranes (Section 5.06.3.9). The synthesis of thiirane 1-oxides and thiirane 1,1-dioxides by oxidation is discussed in Section 5.06.3.3.8 and the synthesis of 5-alkylthiiranium salts by alkylation of thiiranes is discussed in Section 5.06.3.3.4. Thiirene 1-oxides and 1,1-dioxides may be obtained by dehydrohalogenation of 2-halothiirane 1-oxides and 1,1-dioxides (Section 5.06.4.1.2). 

These reactions are thought to proceed by initial formation of the lithio propargylic alcohol adduct, which undergoes a reversible Brook rearrangement (Eq. 9.14). The resulting propargyllithium species can equilibrate with the allenyl isomer and subsequent reaction with the alkyl iodide electrophile takes place at the allenic site. An intramolecular version of this alkylation reaction leads to cyclic allenylidene products (Eq. 9.15). 

Table 9.12 Conversion of lithio propargyl chloride to allenic carbinols and homopropargylic alcohols.

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). 

As the simultaneous creation of Ge = C and P = C double bonds are unlikely, the P = C double bond, much less reactive than the Ge = C double bond, was formed first.173196 was prepared by debromofluorination of 197 [obtained by reaction of ArP = C(Br)Li181 with dimesityldifluorogermane] with ft-butyllithium at low temperature (Scheme 42). The reaction, followed by 31P NMR between -90°C and room temperature, showed the immediate formation of the lithio compound 198, which lost LiF at -60°C to give the germaphosphaallene 196 in 65-70% yield. 196 was stable at -50°C and dimerized slowly above this temperature. It was the first allenic compound of germanium to be characterized by physicochemical methods. 

Lithio-l-methoxyallene 183 ° , readily accessible by deprotonation of methoxyal-lene with n-butyllithium in diethyl ether, turned out to be a versatile C-3 building blocL It adds to aldehydes and ketones giving hydroxyaUcylated allenes 184, which undergo a ring-closure reaction under basic conditions. Thus, 3-methoxy-2,5-dihydrofurans 185 are obtained. Subsequent acid hydrolysis leads to the formation of dihydro-3(2//)-... 

A stereochemical behavior similar to that of the 1-bromo-l-lithio aUcene 164 with regard to chiral aldehydes is shown by the hthiated methoxyallene 183. When added to iV,iV-dibenzylated a-aminoaldehydes 188, it reacts with non-chelate control so that awh -carbinols 189 are obtained predominantly. Diastereomeric ratios of 189 190 range from 80 20 to 95 5. As outlined above, the hydroxyalkylated allenes 189/190 can be converted into furanones 191/192 upon treatment with potassium f-butoxide and subsequent acid hydrolysis" . When, on the other hand, the adducts of 183 to the aldehydes 193 are submitted to an ozonolysis, A-protected a-hydroxy-/3-amino esters 194/195 result (Scheme 25)"" . 

Methylenomycins.1 The cyclopentannelation reaction (12,310) has been modified to provide a general synthesis of methylenomycins. Thus, the adduct (2) of a-lithio-a-(methoxymethyl)allene (1) with 3-methyl-3-butene-2-one cyclizes to methylenomycin B (3) in the presence of trifluoroacetic anhydride and 2,6-lutidine. 

Metallation of allerns Allene is metallated at C, by n-butyllithium in THF at — 78°. In the absence of HMPT, the lithio derivative can be alkylated to give a 1-alkylallene (86-93% yield). Under the same conditions, a 1,1-dialkylallene is convertible into a pure 1,1,3-trialkylallene, but a 1-alkylallene is metallated at C, or C3, depending on the size of the alkyl group. When R contains more than four carbons, metallation is largely at C3. Metallation of 1,1,3-trisubstituted allenes requires t-butyllithium or n-butyllithium + 1 equiv. of HMPT 1,1 -dimethyl-3,3-di-w-butylallene can be prepared in this way in 86% yield. 

Other 3-substituted l-lithio-l-(methoxymethoxy)allenes such as compounds 747-749 have been used in the synthesis of cyclopentenones. The intermediate 747 and an amide have been used for the synthesis of A7-10-chloro-15-deoxy PGA1 ethyl ester1079 and, by reaction with a trifluoromethyl dienone, for the synthesis of 15-deoxy-12-hydroxy-10-(trifluoromethyl)- A7 PGA1 ethyl ester1080. A combination of allenyllithiums 740, 748 and 749 with amides allowed the parallel chemical synthesis of cyclopentenones1081. 

Ethynyl-l,3-dithiane when treated with 1.1 equiv. of n-butyllithium then with methyl iodide af-fords- - only the y-products as a 1 1 mixture of alkyne and allene, resulting from the direct methylation of the lithioalkyne and of the "y-methylation of 2-ethynyl-2-lithio-l,3-dithiane respectively (Scheme 72,... 

Several interesting approaches to the synthesis of /I-ketophosphonates have recently been described. Typically, standard Arbuzov synthesis of /1-ketophospho-nates is unsatisfactory due to a competing Perkow reaction [51]. However, y,d-unsaturated /1-ketophosphonates are obtained in high yield via Arbuzov reaction of triethyl phosphite with a-iodoenones, readily available from tertiary allenic alcohols [52]. Another successful example of an Arbuzov-based approach involves reaction of bromoacetylated polystyrene with triethyl phosphite, which provided immobilized /J-ketophosphonate in excellent yield [53]. In another approach, the lithio derivative of dimethyl methylphosphonate was reacted with Weinreb amide to obtain the corresponding /J-ketophosphonate [54]. a,a-Diflu-oro-a-ketophosphonates have been synthesized via a cerium-mediated route... 

The synthesis of alkylidene and allylidene cyclopropanes reported in this section takes advantage of the availability 77 78,81 a-82) of l-(l-silyl) cyclopropyl carbinols from a-lithio cyclopropylsilanes and carbonyl compounds. It, however, suffers from the sometimes modest yields obtained when ketones are involved (Schemes 21 a, 47) in the Peterson olefination reaction 77,78,81a) (Schemes 21, 48). This reaction seems much more difficult to achieve than when straight-chain analogs are involved and resembles the cases of allenes 1211 and chlorocyclopropenes120) reported by Chan. For example, thionyl chloride alone is not suitable for that purpose 77,136) but further addition of tetra-n-butylammonium fluoride (20 °C, 15 hrs) leads to the formation of undecylidene cyclopropane77,136 in 46% yield from the corresponding l-(l-silyl)cyclopropyl... 

The dilithium salt of the corresponding dimethylpropargylic alcohol 148 interestingly adds ethyllithium in a different manner. The primarily formed 2,3-dilithio-2-pen-tenolate 149 obviously eliminates lithium hydride which attacks the allene intermediate 150 splitting off lithium oxide in an Sj 2 reaction. The endproduct, an EIZ-mixture of 3-lithio-2-methyl-2,4-hexadiene 757 finally was obtained in 30% yield The last step was independently shown to take place by treating the corresponding allenic alcoholate with lithium hydride... 

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