Deprotonation regioselective

Florio et al. have employed heteroaromatic rings as organyl-stabilizing groups for metalated aziridines as well as for metalated epoxides. Regioselective deprotonation of aziridine 246 with n-BuLi, followed by addition of Mel, gave aziridine 247 (Scheme 5.62) [88]. 

The oxidation of 2,5-disubstuted furans by singlet oxygen was exploited for the synthesis of [5,5,5] and [6,5,6] bis-spiroketals <06OL1945>. An unusual regioselective photooxidation of 3-bromofuran to 2- and 3-bromo- hydroxybutenolides, as depicted below, was reported. The mechanism for the observed base-dependent regioselective deprotonation of the endoperoxide intermediate was not determined <06OL4831>. 

Analogously, 5-tributylstannylimidazole 29 was easily obtained from the regioselective deprotonation of 1,2-disubstituted imidazole 28 at C(5) followed by treatment with tributyltin chloride [24]. In the presence of 2.6 equivalents of LiCl, the Stille reaction of 29 with aryl triflate 30 afforded the desired 1,2,5-trisubstituted imidazole 31 with 2,6-di-tert-butyl-4-methylphenol (BHT) as a radical scavenger. Reversal of the nucleophile and electrophile of the Stille reaction also provided satisfactory results. For example, the coupling reaction of 5-bromoimidazole 33, derived from imidazole 32 via a regioselective bromination at C(5), and vinylstannane 34 produced adduct 35 [24],... 

Electrogenerated bases (see Chap. 14) can be prepared in situ and tailored for regioselective deprotonation. Regioselective alkylation of an unsymmetrical cyclic ketone was achieved by using an electrogenerated triphenylmethyl anion (Eq. 5, RX = CH3I,... 

Two consecutive enolate alkylations were utilized to generate the quaternary carbon atom (Scheme 38). Alcohol 238 was transformed into the protected hydroxy enone 244. Regioselective deprotonation at the a-position of the ketone 244 led to a cross-conjugated enolate that was alkylated with the allylic iodide 245. The vinyl silyl moiety in 245 represents a masked keto group [127]. The choice of the TBS protecting group for the hydroxyl group at of 244 was crucial in order to prevent the deprotonation at the y-posi-... 

A regioselective deprotonation with amide base by preferential abstraction of the a-methylene hydrogen syn to the phenylaziridyl moiety in 116 and subsequent decomposition of the resulting monoanion furnishes, with extrusion of styrene and nitrogen, the alkyllithium 118. After abstraction of the amine proton, the c -alkene 117 is formed with regeneration of the lithium amide base for further use in the catalytic cycle. 

Regioselective deprotonation of a, fi-enones.1 This base selectivily deproton-ates cyclic a,(3-enones at the y-position rather than the a -position. 

Thiophene sulfonamide DoM chemistry is by far the most highly explored in view of the agrochemical significance of the sulfonylurea herbicides [23]. Potential for regioselective deprotonation as a function of kinetic or thermodynamic control 38 may lead to 3- or 5-... 

In Se2 -front type electrophilic substitutions via SAMP-/RAMP-hydrazones the less substituted a carbon atom is regioselectively deprotonated. Under the standard reaction conditions (lithium diisopropylamlde, 0°C, ether or THF) the intermediate aza enolates are formed as the CN sPec es> as confirmed... 

Regioselective deprotonation of ironphosphonate complexes have been reported. Depending on the phosphonate, 1,3-migration of phosphonate or ring alkylation of the anion is observed (Schemes 157-158). 

Depending on reagent and reaction conditions, 2- and 4-trifluoromethylpyridines can be regioselectively deprotonated and reacted with electrophiles in good yield <03EJO1569>. Deprotonation was followed by carboxylation with COj and acid hydrolysis. 

The previous cycloaddition reaction discussed is believed to proceed through an aldimine anion (19). Such delocalized anions can also be generated by treatment of suitable aldimines with a strong base. Subsequent cyclocondensation with a nitrile produces imidazoles [25-28]. The 2-azaallyl lithium compounds (19) are made by treatment of an azomethine with lithium diiso-propylamide in THF-hexane ( 5 1) (Scheme 4.2.9) [29. To stirred solutions of (19) one adds an equimolar amount of a nitrile in THF at —60°C. Products are obtained after hydrolysis with water (see also Section 2.3). If the original Schiff base is disubstituted on carbon, the product can only be a 3-imidazoline, but anions (19) eliminate lithium hydride to give aromatic products (20) in 37-52% yields (Scheme 4.2.9). It is, however, not possible to make delocalized anions (19) with R = alkyl, and aliphatic nitriles react only veiy reluctantly. Examples of (20) (Ar, R, R, yield listed) include Ph, Ph, Ph, 52% Ph, Ph, m-MeCeUi, 50% Ph, Ph, p-MeCeUi, 52% Ph, Ph, 3-pyridyl, 47% Ph, Ph, nPr, 1% [25]. Closely related is the synthesis of tetrasubstituted imidazoles (22) by regioselective deprotonation of (21) and subsequent reaction with an aryl nitrile. Even belter yields and reactivity are observed when one equivalent of potassium t-butoxide is added to the preformed monolithio anion of (21) (Scheme 4.2.9) [30]. 

A novel method has been reported for the elaboration of carbonyl compounds, which is discussed in Section 2.1.4.2. ° However, one of the examples falls into the present category the transformation of cyclohexanone to keto alcohol (4), via enamidine (1 equation 1). Treatment of (1) with r-butyllithium effects regioselective deprotonation of the vinylic hydrogen to give (2), which adds to propanal to give (3). Hydrolysis then provi s keto alcohol (4). ° ... 

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