Alkylation double

Ethyl acetoacetate may also be subjected to double alkylation Show how you could prepare 3 methyl 2 butanone by double alkylation of ethyl acetoacetate ... 

Cycloahphatic diamines such as (13) [115172-12-8] which retain some aromatic character have been made from end-ring hydrogenation (44) of l,3-bis(p-aminocumyl)ben2ene [2687-27-6] the double alkylation adduct of aniline to y -diisopropenylben2ene [3748-13-8] (45) using Ru catalysts (46). 

Another possibility is that both nitrogen atoms react with a double alkylating agent. In this way fused pyrazole derivatives (pyrazolo[l,2-a]pyrazoles) like (237) can be obtained by reaction of 3,5-dimethylpyrazole with 1,3-dichloropropane or l-chloro-3-propanol (69BSF2064). More surprising is the reaction with a-chlorocarbonylphenylketene which yields the paraionic compound (238) (80JA3971) which can also be obtained from 3,5-dihydroxy-4-phenylpyrazole and /3-dicarbonyl compounds (82JOC295). 

The stereoselective synthesis of y-bisabolenes was made possible by the development of a new method for the carbosilylation and double alkylation of an acetylenic function coupled with ring closure, overall addition of three carbon substituents to two acetylenic carbons. 

The first polyphosphino maeroeyeles designed speeifieally for use as transition metal binders were reported in 1977 in back-to-baek eommunications by Rosen and Kyba and their eoworkers. The maeroeyeles reported in these papers were quite similar in some respeets, but the synthetic approaches were markedly different. DelDonno and Rosen began with bis-phosphinate 18. Treatment of the latter with Vitride reducing agent and phosphinate 19, led to the tris-phosphine,20. Formation of the nickel (II) complex of 20 followed by double alkylation (cyclization) and then removal of Ni by treatment of the complex with cyanide, led to 21 as illustrated in Eq. (6.15). The overall yield for this sequence is about 10%. 

Other interesting synthetic applications of the ketone-derived enamine alkylation are found in the monomethylation of steroid enamines (249), extension of the benzylation reaction (250) to a ferrocene derivative (251), the use of a-bromoesters (252) and ketones (252) or their vinylogues (25J), in the syntheses of alantolactone (254-256), isoalantolactone (257), and with a bridged bis-enamine (258). The use of bifunctional alkylating agents is also seen in the introduction of an acetylenic substituent in the synthesis of the characteristic fragrant constituent of jasmine (259), the synthesis of macrocyclic ketolactones (260), the use of butyrolactone (261), and the intermolecular or intramolecular double alkylations of enamines with dihalides (262). 

The products of these double-alkylation sequences in the j8-carboline series, 2,9-dialkyl-j8-carbolinium salts, react with base to yield the corresponding quaternary hydroxides. Pyrolysis of the salts leads to dealkylation at the pyr-N with the production of the corresponding ind-A-alkyl-j8-carbohnes. ... 

Besides a polymerization of the Michael acceptor, a double alkylation of the starting ketone, by reaction with a second Michael acceptor molecule, may take place as a side reaction, and thus further reduce the yield. The polymerization of the enone 2 as well as the double alkylation of the starting ketone can be avoided by application of a modern procedure for the Robinson annulation that uses an organotin triflate as catalyst." ... 

A further simplification of the requirements for activity came from the preparation of two spasmolytic agents that completely lack the aromatic ring. Thus, double alkylation of phenylace-tonitrile (54) with 1,5-dibromopentane leads to the corresponding cyclohexane (55). This intermediate is then saponified and the resulting acid (56) esterified with w,w-diethylethanolamine. Catalytic reduction of the aromatic ring affords dicyclonine (51). ... 

In fact, esters of amino alcohols and 2,2-disubstituted plii iiylacetic acids show useful antitussive activity the mecha-lM iii of action may include bronchiodilation. Double alkylation III the anion of phenylacetonitrile with 1,4-dibromobutane gives llit i cyclopentane-substituted derivative (33). Saponification... 

In an effort to more closely mimic the aromatic substitution pattern found in morphine (see A) the pethidine analog containing the m-hydroxy group was prepared as well. Thus, in a synthesis analogous to that used to prepare the parent compound, double alkylation of m-methoxyphenylacetonitrile with the chloroamine. 

Saito et al. achieved the first direct confirmation of double alkylation of purine bases by azinomycin B [140]. They incubated azinomycin B with the self-comple-mentary DNA duplex d(TAGCTA)2 and monitored the reaction by HPLC and ion spray MS. They observed initial formation of a monoadduct that was then converted into a crosslinked bisadduct. The crosslink position was identified as between the guanine of one strand and the 5 -adenine on the other strand by thermo-lytic depurination. Further decomposition prevented structural analysis of the azi-... 

A number of NH phosphinous amides have been P-alkylated by previous conversion to their corresponding anions [59,74]. A particular case of double alkylation takes place with the anion derived from the AT-phosphino phosphinous amide NH(PPh2)2 yielding the diphosphonium salt 17 [102] (Scheme 17). When neutral, its methylation is reported to give the P-H phosphazene-phos-phonium salt 18 [103]. 

Bicyclic keto ester (22) was needed for conformational studies. The common atoms are marked ( ) and the obvious disconnections of this symmetrical molecule require double alkylation of cyclohexanone with a reagent such as (23), Double 1,5-diCO disconnection of (22) is impossible as you will discover if you attempt it. 

The double alkylation of cyclohexanone with (23) is easily carried out in one step via an enamlne. The first alkylation is unambiguous and the second is a cycllsation so occurs very easily. 

Retro synthetic analysis provides two main approaches to the disulfonium-dication functionality. The first approach involves double alkylation of disulfides so far has been unsuccessful (Scheme 5).36 All currently known methods... 

The addition to a double bond is observed in aromatic substrates where the reaction is assisted by chelation. The initial success of such reactions was achieved with the double alkylation of phenol with ethene (Equation (2)).1 This reaction occurs at the or/ -positions selectively by using an orthometallated ruthenium phosphate complex 1. 

The alkylation of the sp3 C-H bonds adjacent to a heteroatom becomes more practical when the chelation assistance exists in the reaction system. The ruthenium-catalyzed alkylation of the sp3, C-H bond occurs in the reaction of benzyl(3-methylpyridin-2-yl)amine with 1-hexene (Equation (30)).35 The coordination of the pyridine nitrogen to the ruthenium complex assists the C-H bond cleavage. The ruthenium-catalyzed alkylation is much improved by use of 2-propanol as a solvent 36 The reaction of 2-(2-pyrrolidyl)pyridine with ethene affords the double alkylation product (Equation (31)). 

Alkylation of a complex such as L2PdCl2 will in many instances lead to double alkylation or a mixture of monoalkyl and dialkyl complexes. A convenient alkylating agent giving purely monomethylpalladium turned out to be tetramethyltin, which has been widely used [12,14], reaction (7), Figure... 

Two examples of three-components coupling reaction are shown in Reactions (7.77) and (7.78) [27,87]. These radical chain reactions proceeded by the addition of an alkyl or vinyl radical onto carbon monoxide, generating an acyl radical intermediate, which, in turn, can further react with electron-deficient olefins to lead, after reduction, to a formal double alkylation of carbon monoxide. These three-components coupling reactions require the generation of four highly disciplined radical species, which have specific functions during the chain reaction. 

A series of heteroatom substituted carbodiphosphoranes C PR2ECH(CF3)2 2 have been prepared in the last 10 years by various groups as shown in Fig. 6. The main synthetic approach consists of the reaction of hexafluoroacetone or thioacetone with the related diphosphines R2P-CH2-PR2 [25, 26]. The bent structure with a P-C-P angle (140°) confirms the double ylidic nature [27] and a related chemistry to C(PPh3)2 is expected however, no reports about coordination activities were reported so far. Theoretically, double alkylation at the heteroatoms of the dianion in Fig. 9 would lead to the substituted carbodiphosphoranes. The amino derivative C(P NMe2 3)2 has a linear structure and was not investigated further [28]. 

The stereoselective introduction of both benzyl groups simultaneously in one step seemed to be particularly attractive for a short synthesis of a- hy-droxylated lactone lignans from malic acid (99). Such a simultaneous double alkylation requires the formation of a chiral l,3-diene-l,4-diolate, which was not known. On the other hand, achiral 1,3-diene-1,4-diolates (di-enolates) have been previously prepared by Garrett et al. [58] and subsequently employed for the synthesis of racemic lignans by Snieckus [59] and Pohmakotr [60]. With knowledge of the synthesis and reactivity of di-enolates, we planned to prepare chiral di-enolates from dioxolanones and to alkylate these di-enolates in a stereocontrolled manner (Scheme 22). For the development of the described double deprotonation/alkylation strategy, tert-hutyl... 

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