Acidic workup

Oxime 26 was prepared from 5,ll-dihydro-dibenzo[a,d]cyclohepten-10-one. The Hoch-Campbell reaction of 26 with 3-dimethylaminopropylmagnesium bromide produced aziridine 27 in 46% yield after acidic workup. Extension of the Hoch-Campbell reaction to steroids has also been reported. Thus, treatment of 3(3-hydroxy-5-pregnen-20-one oxime (28) with methylmagnesium iodide furnished a mixture of diastereomers, 20ot/20P,21-imino-20-methyl-5-pregnen-3P-ol (29) in a 50% combined yield and a 3 1 ratio. On the other hand, homo-adamantan-4-one oxime (30) was transformed to homo-adamantano[4,5-b]-2 -ethylaziridine (31) in 76% yield upon the action of... 

Both 1- and 2-naphthylhydrazine have been shown to react in good yield with 2-hydroxy-3-naphthoic acid in the presence of sodium bisulfite to give, after acidic workup, dibenzocarbazole 30 and 31, respectively7 When either 1- or 2-naphthylhydrazine is heated with sodium bisulfite, dibenzocarbazoles 32 and 31, respectively, are isolated after acidic work-up7 It is suggested that loss of the hydrazine residue to form a bisulfite addition compound of the parent naphthol occurs initially further reaction of this adduct with naphthylhydrazine then affords, after work-up, the products. 

The reactivity of the chloromethyl group is illustrated by the reaction of 2,5-dimethyl-3,4-dichloromethylthiophene (174) with water, which gives (175) Another example of ether formation, is the formation of (176) upon normal acidic workup of the reaction product from 2-thiophenemagnesium bromide and 2-thiophenaldehyde. With... 

Diketones 1 can be converted into the salt of an a-hydroxy carboxylic acid upon treatment with alkali hydroxide after acidic workup the free a-hydroxy carboxylic acid 2 is obtained. A well-known example is the rearrangement of benzil (R, R = phenyl) into benzilic acid (2-hydroxy-2,2-diphenyl acetic acid). The substituents should not bear hydrogens a to the carbonyl group, in order to avoid competitive reactions, e.g. the aldol reaction. 

Tertiary magnesium alkoxides 20, bearing a /3-hydrogen, may undergo a dehydration reaction upon acidic workup, and thus yield an alkene 21 ... 

Such diazo compounds 3 however, that contain two electron-withdrawing substituents, are unstable under these reaction conditions. They further react by hydrolytic cleavage of one carbonyl substituent to give an anionic species 6, that is stabilized by resonance, and which yields the hydrazone 4 upon acidic workup ... 

In general the Stork reaction gives moderate yields with simple alkyl halides better yields of alkylated product are obtained with more electrophilic reactants such like allylic, benzylic or propargylic halides or an a-halo ether, a-halo ester or a-halo ketone. An example is the reaction of 1-pyrrolidino-l-cyclohexene 6 with allyl bromide, followed by aqueous acidic workup, to yield 2-allylcyclohexanone ... 

Generally, both sodium methoxide and ethoxide are employed as basic catalysts, but sometimes potassium methoxide or sodium hydride67 is used. The alkali salts of the dicarboxylic acids are primarily formed, due to the basic reaction conditions, but after acidic workup the free acids are obtained in 20-60 % yield. Reesterification65 of the acids can be performed (see Section 2.1.4.3.). This method can also be applied to the synthesis of hetarenothiepins such as furanothiepins.67... 

John Ward has functionalized an indane using method D in route to tetra-petalone A (46) (Fig. 4.24).25 The o-OBoc benzyl alcohol 44 undergoes addition with two equivalents of Grignard and affords after acidic workup the phenolic indane 45 in 73% yield. Because of steric effects, only one diastereomer is observed after hydrolysis of the enol ether and thermodynamic equilibration of the... 

Methyl 2-chloro-2-cyclopropylideneacetate (4) was readily prepared in two steps from ethylene and tetrachlorocyclopropene [7], and reacted with 4-methylcyclohexa-l,3-dien-2-ol trimethylsilyl ether (62a) at 60 °C to give a complex mixture containing about equal amounts of both regioisomeric adducts 63a, 64a besides the tricyclic ketoester 65a after acidic workup (Schemes 12 and 13) [15]. Each regioisomer was a mixture of endo and exo-diastereomers. The trimethylcyclohexadiene 62b yielded, after 2 days at 100 °C and acidic work-up, the tricyclic ketoester 65b as the main product (Schemes 12 and 13) [15]. 

Fig. 29). The complex was prepared in good yields by the reduction of [Ni2(L21)] (C104)2 with NaBH4 in MeOH followed by acidic workup. 

The bisfunctionalization of alkynes by both C02 and another electrophile can also be achieved, as shown in Scheme 9.17,17a The titanium-carbon bond in the titanacycle complex 31, which was formed by reaction of C02 with the titanacyclopropene 30, can be substituted with various electrophiles. For example, its reaction with NBS or I2 afforded the synthetically useful vinyl bromide or iodide 32, respectively, while the reaction with D20 yielded the /3-deuterated a,/ -unsaturated carboxylic acid. When an aldehyde such as PhCHO was used as an electrophile, butenolide 33 was produced after acidic workup. 

Similar to 67, the oxanickelacycle 69 prepared from 3-hexyne, Ni(cod)2/bipy, and C02 also acted as a nucleophilic reagent. The reaction of 69 with p-tolyl disulfide took place at the Ni-C bond to give vinyl sulfide 70 in 53% yield after esterification (Scheme 23).37 In the case of 2-bromopropiophenone as an electrophile, the cycloadduct 71 was obtained in 47% yield after acidic workup. 

W(CO)6 in toluene at room temperature gave the tricyclic adduct 190a in 94% yield after acidic workup. This reaction forms the tungsten-containing azomethine ylide 191, which undergoes the [3 + 2]-cycloaddition with 189a. The rhodium(n)-catalyzed cyclization of the ene-yne-aldimine 192 with alkene 193 into the cyclopropane 194 was reported by Uemura and Ohe (Scheme 32).42c... 

The important feature of this reaction system is its experimental simplicity.105 Although hydrogenation requires elevated pressure and high temperature, this reaction can be carried out at room temperature in an inert atmosphere. The catalyst can be activated before the addition of the substrate or, even more conveniently, in the presence of the substrate. After completion of the reaction and the subsequent acidic workup, the secondary amine product can be obtained in high yield and purity as well as very high enantioselectivity. 

Several groups intercepted the indole-palladium complex that is initially obtained on cyclization by a subsequent Heck reaction. As will be seen, this can be a powerful elaboration of indoles. In the first example of this concept, Utimoto and co-workers ambushed intermediate 354 with a series of allylic chlorides to give 355. Normal acid workup yields the corresponding C-3 unsubstituted indoles (52-83%) [310]. 

Treatment of thiophene r-butyl sulfonamide (59) with 2 equivalents of n-BuLi formed a dianion in which the second anion resided at the C(5) position. Quenching the resulting dianion with triisopropylborate followed by acidic workup furnished thienylboronic acid 60, which was then coupled with p-bromobenzyl alcohol under basic conditions to afford arylthiophene 61 [49]. 

Snieckus et al. enlisted a combination of directed orrAo-lithiation and Suzuki coupling to assemble some unsymmetrical heterobiaryls [22], Carboxamidophenylboronic acid 30 was derived from sequential metalation of amide 29 and treatment with B(OMe)3 followed by acidic workup. Hetero cross-coupling of 30 with 2-bromothiazole occurred smoothly to furnish phenylthiazole 31. Similarly, a hetero cross-coupling between 2-bromothiazole and 3-formyl-4-methoxyphenylboronic acid produced a heterobiaryl as an intermediate of an orally bioavailable NKi receptor antagonist [23]. 

Vicarious nucleophilic substitution of nitroarenesThe carbanion (2, NaOCH,) of 1 reacts with p-chloronitrobenzene to give, after acidic workup, 5-chloro-2-nitrobenzyl p-tolylsulfone (3). The reagent 2 is typical of a number of carbanions which can undergo nucleophilic substitution ortho or para to nitro-... 

The synthetic usefulness of reactions of lithiated methoxyallene 42 with suitable electrophiles was demonstrated by several syntheses of bioactive natural products or substructures thereof [52-58]. An interesting application was described by Fall et al. [52] after addition of alkyl iodide 55 to lithiated methoxyallene 42, deprotonation by tert-butyllithium and addition of carbon dioxide occurred at the terminal y-carbon and thus provided butenolide 57 after acidic workup. Desilylation of this intermediate with TBAF finally gave bicyclic oxepane derivative 58 in good overall yield (Scheme 8.14). 

Regioselective condensations of vinylallenones with enamines gave highly substituted arylsilanes 203 after acidic workup [171]. 

Deprotonation of a methylene group in 2d followed by reaction with carbon dioxide and acidic workup yielded a racemic mixture of (3,5-di-ter -butylpyrazol-l-yl)(3, 5 -dimethylp5rrazol-l-yl)acetic acid (Hbpa ) (3d) (Scheme 14). Reaction of 3d with base and anhydrous ZnCl2 5delded [Zn(bpa )Cl] that crystallized as a cross-linked dimer [(bpa )ZnCl]2 (16) (Scheme 15, Fig. 16). 

As reported by Steel et al. three structural isomers of bis(camphor-pyrazol-l-yl)methane (21a, 21b and 21c) are formed by coupling of camphorpyrazole 10 [i.e., (4S,7i )-7,8,8-trimethyl-4,5,6,7-tetrahydro-4,7-methano-l(2)H-indazole] with CH2CI2 (121). Isomer 21c can be separated from the other two structural isomers by crystallization or column chomatography. Deprotonation at the bridging carbon atom, subsequent reaction with carbon dioxide and acidic workup yields the enantiopure bis(camphorpyrazol-l-yl)acetic acid Hbpa (8) (Scheme 17, Fig. 19) (116). Due to missing substituents at the p5rrazolyl carbon C5 and a hence likely ortho metallation, isomers 21a and 21b are not suited for his reaction (72). 

Oxidative cleavage of the terminal double bond of 49 by ozonolysis to the aldehyde followed by permanganate oxidation to the acid and esterification with diazomethane produced the methyl ester 50. Dieckmann cyclisation of 50, following the procedure developed in Holton s laboratory (LDA, THF, -78 °C, 0.5 h, then HOAc, THF), gave the enol ester 5J in 93% yield (90% conversion). Decarbomethoxylation of 5J. was carried out by temporarily protection of the secondary alcohol (p-TsOH, 2-methoxypropene, 100%), and heating the resulting compound 52 with PhSK in DMF, at 86 °C (3 h) to provide 53a or, after an acidic workup, the hydroxy ketone 53b. 92% yield. 

Next, the TMS enol ether of 53c underwent oxidation with MCPBA to trimethylsilyloxy ketone 57. in 86% yield (86% conversion). Addition of methylmagnesium bromide in methylene chloride proceeded in almost quantitative yield (95%) to give tertiary alcohol 58. Dehydration with Burgess reagent [19] and acidic workup provided the allylic alcohol 59a in 63% yield, which was converted... 

The cyclohexenone C has been prepared in a one-pot process beginning with 4-methylpent-3-en-2-one. The reagents which are added in succession are 4-methoxy-phenyllithium, Li, and NH3, followed by acidic workup. Show the intermediate steps that are involved in this process. 

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