Ammonia, allylic substitution

Scheme 16 Allylic substitution with ammonia to form diallylamines...

Table 5 Allylic substitution with ammonia equivalents...

Protected primary allylic amines were generated from allylic carbonates and ammonia equivalents. Iridium-catalyzed allylic substitution has now been reported with sulfonamides [90, 91], imides [89, 91-93], and trifluoroacetamide [89] to form branched, protected, primary allylic amines (Table 5). When tested, yields and selectivities were highest from reactions catalyzed by complexes derived from L2. Reactions of potassium trifluoroacetamide and lithium di-tert-butyhminodi-carboxylate were conducted with catalysts derived from the simplified ligand L7. Reactions of nosylamide and trifluoroacetamide form singly-protected amine products. The other ammonia equivalents lead to the formation of doubly protected allylic amine products, but one protecting group can be removed selectively, except when the product is derived from phthalimide. 

In contrast, reactions catalyzed by la were typically conducted with added [Ir (C0D)C1]2 to trap the K -phosphoramidite ligand after dissociation, and thereby, to leave the unsaturated active catalyst. Under these conductions, as much as half of the iridium in the system is present in an inactive acyclic species. In contrast, when ethylene adduct lb is used as the catalyst, all of the iridium belongs to the active metalacyclic species. Hartwig and coworkers have recently taken advantage of the increased availability of the active catalyst generated from lb to develop new allylic substitution reactions. These new processes include the reactions of carbamates, nitrogen heterocycles, and ammonia. 

Scheme 27 Allylic substitution with ammonia catalyzed by la and lb...

In a paper pnblished in the early 1950s Touster found that sodio derivatives of many alkyl-substituted heteroaromatic compounds or of allyl-substituted benzenes 30 can be oximated with alkyl nitrites in refluxing anhydrous liquid ammonia at atmospheric pressure... 

Subsequently, Kato and Goto have reported the synthesis of 2- and 4-pyridinecarbox-aldoximes from 2- and 4-picoline with potassium amide and amyl nitrite in liquid ammonia at — 33°C, although they failed to obtain either of these oximes when the reaction was carried ont with sodium amide in liquid ammonia at room temperature in a sealed tube. Finally, in 1964, aUcyl-substituted heteroaromatic compounds and allyl-substituted benzenes were oximated in liquid ammonia at —33 °C with sodamide and an alkyl nitrite . 

Since allyl azides are readily reduced to primary allylamines40, sodium azide is another useful ammonia equivalent in palladium(0)-catalyzed allylic substitutions. Water has to be added as a cosolvent to dissolve sodium azide. Highly diastereoselective transformations are achieved, especially with phosphates, using Pd2(dba)3 CHCl3/l,4-bis(diphenylphosphino)butane [dppb] as the catalyst40, as shown in Table 4. 

In allylic oxidation, an olefin (usually propylene) is activated by the abstraction of a hydrogen a to the double bond to produce an allylic intermediate in the rate-determining step (Scheme 1). This intermediate can be intercepted by catalyst lattice oxygen to form acrolein or acrylic acid, lattice oxygen in the presence of ammonia to form acrylonitrile, HX to form an allyl-substituted olefin, or it can dimerize to form 1,5-hexadiene. If an olefin containing a jS-hydrogen is used, loss of H from the allylic intermediate occurs faster than O insertion, to form a diene with the same number of carbons. For example, butadiene is fonned from butene. 

However, it is worth returning to the chemistry of hexamethylenetetramine (1,3,5,7-tetraazaadamantane or l,3,5,7-tetraazatricyclo[3.3.1.H ]decane, C6H12N4, Chapter 9 and Table 10.2) that is formed by the condensation of ammonia (NH3) with methanal (formaldehyde, H2OO). As was noted as early as 1895 by M. Delepine, in a reaction now bearing his name, alkyl halides react with hexamethylenetetramine to produce A-substituted derivatives of the hexamethylenetetramine, which can then be hydrolyzed to aldehyde, ammonia, and substituted amine. Not unexpectedly, it has become clear that benzyhc and allylic halides react best (Scheme 10.30). 

ALCOHOL represents a convenient method of converting allyl alcohol to 2-substituted 1-propanols, while a one-pot reaction sequence of alkylation (alkyl lithium) and reduction (lithium—liquid ammonia) provides excellent yields of AROMATIC HYDROCARBONS FROM AROMATIC KETONES AND ALDEHYDES. 

The reaction that leads to allylamine is nucleophilic substitution by ammonia on allyl chloride. 

Direct transformation of thiazoline-azetidinones 2 into 3 -thio-substituted cephalosporins 6 has been performed by ring opening of the thiazoline moiety with sulfenyl chloride followed by ring closure with ammonia in dimethylformamide and simultaneous displacement of the allylic chlorine atom with the leaving thiolates. 

Hence, N,N-diallyl-(2-chlorophenyl)-amine and N-allyl-N-(2-chlorophenyl)-acetamide react with MesSn and Ph2P ions in liquid ammonia under photostimulation to afford cyclized-substituted compounds in good yield (Scheme 10.51) [67]. 

When 7V-allyl-(2-chloro-phenyl)-amine 23 (Z = NH) is allowed to react with Me3Sn ions in liquid ammonia, a low yield of product 24 (Z = NH) is obtained (Sch. 24). When the amino group is protected as 23 (Z = TV-allyl, Wacetyl derivatives), good yields of ring closure—substitution products 24 (Z = Wallyl, TV-acetyl) are obtained [98]. 

In order to determine the degree of competition between both processes, the photo -stimulated reaction of the radical probe 3-bromo-2-tetrahydropyranyl allyl ether (83) with Ph2P ions in liquid ammonia was studied. In this reaction both the substitution 84 (20% yield) and the cyclized 85 (69% yield) substitution products were formed (equation 67)54,151. 

The use of 1,1-diiodomethane as an electrophile in the Birch reduction (with lithium in liquid ammonia) of electron-deficient pyrroles 915 furnished pyrrolines 916 (in high to excellent yields), which provided access to the synthetically important functionalized 5,6-dihydro-2(l//)-pyridinones 917 (via radical ring expansion), substructures commonly found in biologically active natural products (Scheme 177) <2004CC1422>. 2-(Chloroalkyl)-substituted pyrrolines 919 were duly prepared by the reductive alkylation (with l-chloro-3-iodopropane or 1-chloro -iodobu-tane) of electron-deficient pyrrole 918. Allylic oxidation then furnished lactams 920 (Scheme 178). 

A definite improvement in the synthesis of A -methoxy aziridines was achieved by substituting boron trifluoride with trimethylsilyl triflate and diethyl ether with dichloromethane"9. In this way, the A -methoxy aziridines were obtained in good yields from a variety of linear and cyclic alkenes, e.g., 6-8. For comparison, the aziridine 8 was obtained in 50% yield by using boron trifluoride- diethyl ether complex in dichloromethane. Complex product mixtures were obtained with allyl and crotyl alcohols and with cyclohexenone. Further transformation of the A -methoxy aziridines into the N-H aziridines was possible using sodium/ ammonia reduction, e.g., 9. 

When diethyl tetracyanocyclopropane-l,l-dicarboxylate (6), a cyclopropane derivative with six electron-withdrawing groups, was treated with ammonia in diethyl ether, the reaction took an unforeseen course cleavage of the tetracyano-substituted bond occurred and one of the ester functions was eliminated to give a stabilized allyl anion 1 ... 

Star and dendrimer core molecules were prepared by the peralkylation or allylation of cyclopentadienyliron complexes containing methyl-substituted arenes.298,301,302,304-311,333 The preparation of water-soluble metallodendrimers containing six cationic cyclopentadienyliron moieties, 281, has also been reported.301 Dendrimer 281 was tested for potential use as a redox catalyst for the cationic reduction of nitrates and nitrites to ammonia. 

The pyrrolinyl- (6-11) and pyrrolyl-substituted (12-13) eudistomin skeletons were first prepared by Rinehart from 1-cyano-P-carboline (145), which can be obtained from the corresponding acid (28). Grignard reaction with appropriately protected 3-bromopropanal (Scheme 4) provided the necessary carbons with appropriate oxidation level for cyclization to either of these ring systems. The pyrrolyl-substituted eudistomins then result upon hydrolysis of the imine and acetal functions with concomitant cyclization in the presence of ammonia. The pyrrolinyl-eudistomins require reduction of the imine to the amine followed by acetal hydrolysis and simultaneous ring closure to isomer 147. Reduction of the imine 147 followed by allylic oxidation with sodium hypochlorite isomerizes 147 to the pyrrolinyl-eudistomin skeleton (149). 

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