Equivalents ammonia equivalent

Other PK variations include microwave conditions, solid-phase synthesis, and the fixation of atmospheric nitrogen as the nitrogen source (27—>28). Hexamethyldisilazane (HMDS) is also an excellent ammonia equivalent in the PK synthesis. For example, 2,5-hexanedione and HMDS on alumina gives 2,5-dimethylpyrrole in 81% yield at room temperature. Ammonium formate can be used as a nitrogen source in the PK synthesis of pyrroles from l,4-diaryl-2-butene-l,4-diones under Pd-catalyzed transfer hydrogenation conditions. 

Dibromobenzothiadiazole 89 can also undergo asymmetric stepwise Buchwald amination with various anilines (Scheme 12) <2002TL9009, 2005JOC2754>, and 4-bromo-7-methylbenzothiadiazole 91 can be aminated using benzophe-none imine as an ammonia equivalent via a two-step palladium-catalyzed amination route (Scheme 13) <2003JHC713>. 

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. 

Catalyst activation became a necessity when reactions with bulky aliphatic amines and arylamines (cf Section 9.4.2) as nucleophiles were probed. It was also required for intramolecular aminations [8,18]. Thus, with Ph2CHNH2, an ammonia equivalent, conversion was only 11% upon application of procedure (a) (Table 9.2, entry 11), while the reaction promoted by the activated catalyst proceeded with high selectivity and yield. Catalyst activation is faster with ligand L2 than LI, and accordingly in situ activation occurs more readily for the former (cf entries 10 and 12). Examples presented in entries 16-20 further demonstrate the advantages of catalyst activation [53] (note that excellent results can be achieved with the simpH-fied ligand L5a). 

The additions of ammonia equivalents, i.e. nitrogen nucleophiles like dibenzylamine (Scheme 27) which are essentially a protected primary amino group, are of special synthetic interest with respect to their possible subsequent chemical transformations. Poorly nucleophilic ammonia equivalents like acetamide or the classical phthalimide, did not add or originally gave low yields of 92a (Scheme 28) [9],but later phthalimide was found to add to 1-Me very well under mild conditions [53]. However, the a-chlorine in 92a could neither be substituted nor could the phthalimido group be cleaved without destroying the cyclopropane ring. The potassium bis(alkoxycarbonyl)amides (Boc)2NK and (Moc)(Boc)NK add to 1-Me in satisfactory yields, but the a-chlorine atom in... 

Surprisingly though, the rather weakly nucleophilic (diphenylmethylene) amine (DPMA-H) and its cyclopropyl analog (cyclopropylphenylmethylene) amine (CPMA-H) 93 [8, 9, 10 c, 21b, 22b, 58-601 which can also serve as ammonia equivalents, add to 1-R and 2-R cleanly and in most cases quantitatively in a 1,4-fashion (Scheme 29). 

Scheme 28. Addition of ammonia equivalents onto the chloro ester 1-Me [9,53]...

As a potential approach towards enantiomerically pure amino acids containing a cyclopropane ring, Michael additions of enantiomerically pure chiral ammonia equivalents 95-100 have been examined (Fig. 5). 

A solution to this problem was found by using (4Ry 5S)-4,5-diphenyloxazoli-dine-2-one (100) [63] which turned out to be a suitable chiral ammonia equivalent permitting to achieve good diastereoselectivities with respect to the ste-reogenic center a to the alkoxycarbonyl group especially with 2 -substituted... 

Fig. 5. Chiral cyclic nitrogen nucleophiles 95-100 as potential ammonia equivalents...

Of special interest is the reaction with potassium cyanate (Scheme 34) [11b] which turned out to be essentially a new method of chlorine substitution with a protected ammonia equivalent. 

The double N-arylation of primary amines or ammonia equivalents 592 with 2,2 -biphenylylene ditriflate (591) under Buchwald-Hartwig N-arylation conditions gave the unsymmetrically multi-substituted carbazoles 593. Among the various... 

The synthesis of aromatic primary amides through aminocarbonylation of aryl halides with ammonia is not well documented due to the technical difficulty in using gaseous ammonia. To resolve this problem, methods using ammonia equivalents such as hexamethyldisilazane (HMDS), " formamides, and a titanium-nitrogen complex have been developed. 

Figure 1. The Nitrogenase Reaction. The electron transfer proteins ferredoxin (Fd) and flavodoxin (Fid) serve to couple the nitrogenase reaction to metabolically generated reducing equivalents. Ammonia synthesis requires 8 electrons 6 for the reduction of dinitrogen and 2 for the coupled, obligatory synthesis of H2. These reactions are catalyzed by the terminal component in the complex, the MoFe-protein. The electrons are transferred to the MoFe-protein from the Fe-protein in a process coupled to the hydrolysis of 2ATP/electron (Howard and Rees, 1994,1996).

Note that in the preparation of the above, Rink resin acts as an immobilized ammonia equivalent (RNH2 = Rink amine) and generally gives higher purity products than its solution-phase ammonia counterpart [58]. The cinnamic acid is originally masked as a t-butyl ester in the condensation, only to be subsequently released after TFA treatment. 

Other nucleophiles have been used in this reaction. For example, BINAP was shown to be the best ligand for the enantioselective allylic amination of 19 with sodium diformylamide, a protected ammonia equivalent, furnishing the desired product in good yield and excellent enantioselectivity [96]. Also, a P,N-ligand has been developed for the allylic sulfonylation with good ee but moderate yield [97]. 

Benzophenone inline or allylamine can be used as ammonia equivalents in the CN coupling reactions of halopyr-idines <1996JOC7240,1998TL1313>. Primary S-aminopyrimidines can also be prepared using benzophenone imine as the amine source, as demonstrated by the synthesis of 970 from 968 via 969 <20060PD70>. Aromatic amines also efficiently aminate S-bromopyrimidine (Scheme 115) <2005OL3965>. 

In a related context, 2-(/Koiuenesulfonyl)ethy]amine was used as an ammonia equivalent in an aza-ene reaction by which aldehyde 92.1 was converted to the bicycle 912 [Scheme 8.92].223 After N-acetylation and Pd(0)-catalysed hydro-stannylation, the alkenylstannane 914 dintensed under copper(II) nitrate catalysis. The 2-(p-toiuenesulfonyl)ethyl group was then discharged by p-elimination with potassium rm-butoxide. 

Lim and Lee coupled the binaphthol derivative below with benzylamine to yield the desired product in 75 % yield, Eq. (75) [90]. Subsequent removal of the benzyl protecting groups was effected by hydrogenation, thus demonstrating that benzylamine may be used as an ammonia equivalent. 

Representative Procedure for the Use of Benzophenone Imine as an Ammonia Equivalent (Excerpted with permission from [108]. 1996 Pergamon Press) A Schlenk tube was charged with sodium tert-butoxide (1.4 mmol), Pd2(dba)3 (0.00125 mmol), and BINAP (0.00375 mmol). The Schlenk tube was fitted with a septum and attached to a Schlenk line. After the air atmosphere was replaced with argon, toluene (4 ml), 4-tert-butylbromobenzene (1.0 mmol), and benzophenone imine (1.2 mmol) were added by syringe. After the septum was replaced with a teflon valve, the reaction was sealed and heated to 80 °C with stirring until starting material was consumed as judged by GC analysis. The reaction mixture was cooled to room temperature, diluted with ether (40 ml), filtered, and concentrated. The crude reaction mixture was then recrystallized from MeOH to furnish the desired product in 90% yield. 

The DPPF-catalyst system is also useful in the arylation of the benzophenone-based ammonia equivalent [109]. The coupling of 4-bromoanisole and benzophenone imine proceeded in excellent yield with only 0.5 mol% palladium, Eq. (128). 

Several groups have utilized benzophenone imine as an ammonia equivalent in the palladium-catalyzed cross coupling. For example, Mullen and co-workers prepared a new thermotropic dye via the BINAP/Pd-coupling of the corresponding bromide, Eq. (130) [110]. Similarly, Basu reported the amination of a mixture of bromopyrene derivatives [111]. 

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