Reaction with methyllithium

In contrast to its reaction with methyllithium, jV,Af-diethyl-5-phcnyl-3//-azepin-2-amine (1) with butylithium undergoes 4,5-addition to give 4-butyl-A, V-diethyl-5-phenyl-4,5-dihydro-3/7-azepin-2-amine (2)38. 

In some cases the yields were poor due to competing deprotonation of the substrate by the organolithium reagent. Deprotonation was the predominant reaction with methyllithium or when (Z)-2-(l-alkenyl)-4,5-dihydrooxazoles were employed. The stereochemical outcome has been rationalized as occurring from a chelated transition state. The starting chiral amino alcohol auxiliary can also be recovered without racemization for reuse. 

Ring expansion.1 The adducts (2) of cycloalkanones with 1 on reaction with methyllithium or wc-butyllithium at 0° rearrange to ring-expanded a-phenylthio ketones. 

A route involving trapping the enolate as a silyl enol ether, subsequent transme-tallation to the corresponding lithium enolate and alkylation turned out to be more efficient (Scheme 18.41) [123]. Thus, treatment of 120 with the cuprate 124 and chlorotrimethylsilane furnished the silyl enol ether 125, which was then converted into the desired enprostil derivative 127 with 68% yield over both steps by reaction with methyllithium and the allenic triflate 126. 

Phosphorylated allenes 195 (R1 = H or Me) are a source of secondary ( )-allylamines. The allenes are treated with an amine R2NH2 (R2 = t-Bu or 4-MeCgH4 and the products, which exist as equilibrium mixtures of enamines 196 and imines 197, are olefinated by successive reaction with methyllithium and an aldehyde R3CHO (R = i-Bu, 4-MeCgH4, PhCH2CH2 etc). Reduction with sodium borohydride finally yields the... 

Birch reduction-alkylation of (2S)-2-methoxymethyl-l-(2-phenylbenzoyl)pyrrolidine (1) gives products 2 in high diastereoselectivities29. In contrast to the previous examples, only one double bond remains in the product (if one equivalent of rm-butyl alcohol is used as proton donor). Formally this procedure is a stereoselective cis addition, and is thus particularly useful. Thus, two stereogenic centers are created in the same reaction step with high diastereoselectivities. Subsequent hydrolysis furnishes acids, whereas reaction with methyllithium yields chiral ketones29. 

Reaction with allene sulfoxides.1 Allenic sulfoxides are desulfurized by reaction with methyllithium. An example is the transformation shown in equation (I). The propynylcarbinol 1 is treated with benzenesulfenyl chloride to form the allene 2,... 

The perhydrotetrabromo compound (49) undergoes an interesting rearrangement to the pyrroles (51a) and (51b) on reaction with methyllithium in ether (75JOC47). In this reaction it was shown that pyrrole (51b) arises as a secondary product fromr (51a). Reaction of... 

Compound X, of formula C3H5Br3, with methyllithium formed bromocyclopro-pane and 3-bromopropene. The nmr spectrum of X showed a one-proton triplet at 5.9 ppm, a two-proton triplet at 3.55 ppm, and a complex resonance centered at 2.5 ppm downfield from TMS. What is the structure of X Account for the products observed in its reaction with methyllithium. 

When the carbene or carbenoid resulting from a dihalocyclopropane is unable to rearrange to the al-lene due to steric or other factors, insertion or addition reactions characteristic of carbenes take place. Thus dibromonorcarane on reaction with methyllithium gives a bicyclobutane derivative by insertion of the carbene into a 0-C—H bond (equation 57).178 Allene formation is sterically unfavorable in this case. Similarly, dibromotetramethylcyclopropane gives l,2,2-trimethylbicyclo[1.1.0]butane instead of tetra-methylallene (equation 58).179 181 An example involving a tricyclic dibromocyclopropane is given in equation (59).182... 

In cases such as the one shown in equation (69), what appears to be displacement is more likely a multistep elimination-addition process.37 Carbonyl or sulfonyl groups in the 2-position greatly facilitate each of these two steps. Thus (32) on treatment with alkoxide or thiolate gave the cyclopropane acetal or thioacetal, respectively (equation 70).199 In related work, tetrachlorocyclopropene, which has interesting synthetic potential, is formed from pentachlorocyclopropane by treatment with potassium hydroxide (equation 71).200 Certain 1,1,2-trihalocyclopropanes on reaction with methyllithium in ether at low temperature afford the corresponding halocyclopropenes by 1,2-dehalogenation (equation 72).201 Similarly,... 

Transition structures for the lithium-bromine exchange reaction of 1,1-dibromo-alkenes with methyllithium have been located by both the B3LYP and the MP2 levels of theory with the 6-31+G basis set.67 The reaction with methyllithium dimer gave similar results with lower activation energies. These calculations predict both the kinetic and the thermodynamic stereoselectivity correctly. It has been found that predominantly the sterically more constrained bromine atom of 1,1-dibromoalkenes reacted with alkyllithium (dimer) in the kinetic condition. 

Indole was included with alkyl and arylamines in a study which demonstrated the potential of 2-pyridylsulfonyl as an /v -protecting group. The group is reductively removed using SmI,. <95JOC5969> A possible new means for indole debenzylation was uncovered l-Benzyl-2-phenylindole and several /V-benzylcarbazoles and tetrahydrocarbazoles were found to undergo debenzylation on reaction with methyllithium or LDA. An -elimination mechanism is proposed. <95TL1671>... 

Starting with (+)-26, L-noviose, the sugar moiety of antibiotic novobiocin, was obtained. Thus, (+)-26 was converted into 56, via 41, which on reaction with methyllithium followed by oxidative cleavage and deprotection gave L-noviose (Scheme 16).21... 

Fig (14) Olefin (107) has been converted to cyclic ether (114) by standard reactions. Its transformation to enone (115) is accomplished by annelation with methyl vinyl ketone and heating the resulting diketone with sodium hydride in dimethoxyethane. The ketoester (116) is subjected to Grignard reaction with methyllithium, aromatization and methylation to obtain the cyclic ether (117). Its transformation to phenolic ester (119) has been achieved by reduction, oxidation and esterification and deoxygenation. 

The di-iodides (81), formed from cyclopropenes by addition of iodine with rearrangement also eliminate halogen on reaction with methyllithium, providing a simple route to l-vinyl-2-alkylbicyclo[l. 1. OJbutanes180. 

Methylenemolybdenum reagents. The novel methylenation reagents 1 and 2 are prepared in situ from molybdenum(V) chloride by reaction with methyllithium (equations I and II). 

When [(/ )-(S)-PPFA]PdCl2 is used in the stereoselective hydrosilylation of 1-aryl-1,3-butadienes with trichlorosilane, the chiral (Z)-l-aryl-l-trichlorosilyl-2-butene 17 and the regiomeric 1-aryl-3-trichlorosily 1-1-butene 18 are formed. Subsequent reaction with methyllithium produces the corresponding trimethylsilyl derivatives13. 

Methyl ketones are often directly prepared from carboxylic acids by reaction with methyllithium. Other simple alkyl ketones may also be prepared in the same fashion, making this a method that should be considered whenever these substrates are required. An important demonstration of this protocol was reported by Masamune and coworkers in their synthesis of chiral propionate surrogates (Scheme 13). The ethyl and cyclopropyl ketones are important starting materials for macrolide total synthesis and have been prepared on a large scale. The overall yield for the ethyl ketone is 65% using 3.5 equiv. of ethyllithium without protection of the hydroxy group. 

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