Directed deprotonation

Fluonnated ylides have also been prepared in such a way that fluonne is incorporated at the carhon P to the carbamonic carbon Vanous fluoroalkyl iodides were heated with tnphenylphosphine in the absence of solvent to form the necessary phosphonium salts Direct deprotonation with butyUithium or hthium dusopropy-lamide did not lead to yhde formation, rather, deprotonation was accomparued by loss of fluonde ion Flowever deprotonation with hydrated potassium carbonate in thoxane was successful and resulted in fluoroolefin yields of45-S0% [59] (equation 54) P-Fluorinated ylides may also be prepared by the reaction of an isopropyli-denetnphenylphosphine yhde with a perfluoroalkanoyl anhydnde The intermediate acyl phosphonium salt can undergo further reaction with methylene tnphenylphosphorane and phenyUithium to form a new yhde, which can then be used in a Wittig olefination procedure [60] (equation 55) or can react with a nucleophile [6/j such as an acetyhde to form a fluonnated enyne [62] (equation 56)... 

Hodgson and coworkers have demonstrated that the use of diamine ligands in combination with s-BuLi allows the direct deprotonation/electrophile trapping of... 

Direct deprotonation/electrophile trapping of simple aziridines is also possible. Treatment of a range of N-Bus-protected terminal aziridines 265 with LTMP in the presence ofMe3SiCl in THF at-78 °C stereospecifically gave trans-a, 3-aziridinylsi-lanes 266 (Scheme 5.67) [96]. By increasing the reaction temperature (to 0 °C) it was also possible to a-silylate a (3-disubstituted aziridine one should note that attempted silylation of the analogous epoxide did not provide any of the desired product [81],... 

Full exploitation of the synthetic potential of enolates requires control over the regioselectivity of their formation. Although it may not be possible to direct deprotonation so as to form one enolate to the exclusion of the other, experimental conditions can often be chosen to favor one of the regioisomers. The composition of an enolate mixture can be governed by kinetic or thermodynamic factors. The enolate ratio is governed... 

The 5yn-directed deprotonation of arylhydrazones can be used to reverse the normal preference of the less-substituted vinyllithium. By employing a one-flask dianion alkylation procedure, the formation of an almost exclnsive stereoisomer of acyclic vinyllithinms... 

Although there is a kinetic barrier to the direct deprotonation of tertiary amines, Ahlbrecht and Dollinger showed in 1984 that the Schlosser superbase, i c-BuLi/f-BuOK, can deprotonate A-methylpiperidine selectively on the methyl group (Scheme 3). This superbase probably yields an a-amino-organopotassium species (and f-BuOLi), but treatment with LiBr effects transmetalation to the more nucleophilic, and less basic, a-amino-organolithium species. Electrophilic quench with several aldehydes and ketones gives substitution products in good yields as typified by the example in Scheme 3. Similarly,... 

A-Boc-A -isopropylimidazolidine (175) is deprotonated by the (—)-sparteine method and alkylated to form imidazolidines 176 (equation 41). The yields remain below 50%, since only a part of 175 exists in the shown conformation, which is required for the directed deprotonation. At low temperature, the interconversion between the s-trans- and i-c -conformation is too slow. Ring cleavage furnishes synthetically useful chiral 1,2-diamines 177. 

Consequently, matched/mismatched cases [25] can result, and indeed our investigations on cooperative effects of stereogenic elements in such systems revealed 9 be the matched case and 23 (which is also easily prepared by following a directed deprotonation-silylation-deprotonation-trapping-desilylation sequence [11]) to be the mismatched case in diethylzinc additions to aldehydes [26]. Later, these investigations were extended to more complex systems such as 24 [27], but ferrocene 9 still remains superior to all other compounds. 

First a directed deprotonation takes place. Which regiochemistry do you expect ... 

Convenient alternatives to direct deprotonation of ethers are tin-lithium exchange [199, 258-261], halogen-magnesium exchange [262], or reductive cleavage of 0,Se-acetals [263, 264], Another synthetic equivalent of a-metalated ethers are (alkoxymethyl)phosphonium salts [265]. 

Hodgson, D. M. Norsikian, S. L. M. First direct deprotonation-electrophile trapping of simple epoxides synthesis of a,/f-epoxysilanes from terminal epoxides. Org. Lett. 2001, 3, 461—463. 

The metalation proceeds by initial deprotonation of the amide followed by ortho-directed deprotonation at the C3 position to produce the pseudo six-membered ring organolithium species 5.36. 

The same intermediate was also formed by direct deprotonation of N,N-dimethylthioformamide with LDA, and was used to prepare a-oxo thioami-des by acylation with carboxylic esters [141]. Deprotonation of the formed thioamides laterally takes place on the AT-methyl group and intramolecular addition of the anion to the carbonyl group provides a new entry to /1-thio-lactam rings. 

Halogen-metal exchange is useful particularly for the synthesis of heterocycles bearing lithium at less acidic sites - for example, the 3-position of both pyridine and of the 5-membered heterocycles. The schemes below show the synthesis of some P-lithiated 5-membered heterocycles (a-lithiation can be achieved using direct deprotonation methods - see section 2.2.3). 3-Lithiothiophene 93 in an important intermediate in the industrial synthesis of the vasodilator cetiedil 94.84... 

The reaction of triazolium and benzimidazolium salts with sodium methoxide yields the corresponding methoxy-triazoles and benzimidazoles [30,31], which can be also used as triazolilydene and benzimidazo-lilydene precursors. Notably, adduct formation does not occur for certain unsaturated imidazolium salts with a C = C backbone. For the latter, reaction with KOBu results in direct deprotonation to the free NHC (Scheme 8, also shows the reaction of a dihydroimidazolium salt with KOBu ) [32],... 

The reaction afforded the tandem cyclization product 170 as a mixture of two separable isomers together with an a,p-unsaturated cyclic bisphosphonate, which is formed by a direct deprotonation of the vinylic a-proton of 168 and subsequent intramolecular Michael cyclization. The authors described the formation of 170 by the conjugated addition of 168 to 2.2 equivalents of PhLi and subsequent intramolecular Michael reaction in the intermediate 169. It is likely that coordination of the lithium atom to the oxygens of the phosphonates favors formation of the /raw.v-isomer. As shown in Scheme 52, the reactions with bulky naphthyllithiums gave only the fraws-170 isomer. This novel methodology can provide a rapid entry into a variety of cyclic bisphosphonates in good stereoselectivity. 

Boron, having the electronic configuration s22s22p, has 3 valence electrons, and forms planar, tricovalent derivatives that are electron deficient, and which, as Lewis acids, accept two electrons from bases to complete the boron outer-shell octet and give tetrahedral adducts. Boric acid exemplifies this behavior by ionizing, in aqueous solution, not by direct deprotonation, but by hydration and subsequent ionization, to give the symmetrical borate anion ... 

Enolates, such as 3, are generally formed by direct deprotonation of either its carbonyl ( ) or enol tautomer (2 ), using a Brpnsted base B (Scheme 1). The relative proportion of this enolate to the corresponding parent carbonyl and enol components is largely dependent... 

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