Alkene secondary amine substrates

The oxidative effects of silver(II) complexes of pyridine carboxylates have been studied for a variety of substrates. With ar-amino acids, a rapid reaction occurred at 70 °C in aqueous solution with bis(pyridyl-2-carboxylato)silver(II). 4 The product was the next lower homologous aldehyde and yields were generally greater than 80%. Other substrates included primary and secondary amines, alcohols, monosaccharide derivatives, alkenes, arylalkanes and arylalkanols.90 Only minor differences were detected in efficiencies when 2-, 3- or 4-mono-, or 2,3-di-carboxylates were used as the oxidant. 

Phosphorinanones have been utilized as substrates for the preparation of alkenes,11 amines,12 indoles,5,13 and in the synthesis of a series of secondary and tertiary alcohols via reduction,10 and by reaction with Grignard6,11 and Refor-matsky11,14 reagents. Phosphorinanones have also been used as precursors to a series of 1,4-disubstituted phosphorins.15 The use of 4-amino-l,2,5,6-tetrahydro-l-phenylphosphorin-3-carbonitrile for the direct formation of phosphorino-[4,3-d] pyrimidines has been reported.16... 

Metabolic N-demethylation of methadone occurs since incubation of levo methadone with rat liver slices results in the formation of formaldehyde at a rate only marginally less than that obtained with pethidine as substrate. °2) The reason for the failure of early attempts to isolate the corresponding secondary amine is now well established as due to the facile cyclization of N-desmethylmethadone to a pyrroline derivative. Chemical studies have confirmed the cyclic structure 3 (13) the corresponding free base is an exocyclic alkene 2 that exists as an approximately 50 50 mixture of c-t isomers.(14)... 

Solutions of Group I metals in the lower molecular weight amines are more potent reductants than those in liquid ammonia, and as a general rule substrates are more extensively reduced than by the Birch method. o Naphthalene (49 Scheme 48), for example, is reduced by a solution of lithium in ethylamine to a 1 1 mixture of A W- and A -octalins (214) and (215). If ethylenediamine is employed as the medium, the completely saturated decahydronaphthalene is formed, while the proportion of (215) may be increased to 80% by utilizing a (1 1) mixture of ethylamine with dimethylamine. The formation of the more-substituted alkene appears to be a general result for such primary and secondary amine mixtures and has been used to good effect in the reduction of both toluene and cumene to their 3,4,5,6-tetrahydro derivatives (216) and (217), respectively, in ca. 80% yields. A comprehensive review of these kinds of reducing systems, which also draws comparisons with the Birch method, is available,but more recent-... 

Fukuyama also presented an alternative route to the advanced intermediate 114 as shown in Scheme 18 with an early introduction of the protected amino functionality. Reaction of y-butyrolactone with the Grignard reagent derived from 1,4-dibromobutane (120) afforded diol 121. Mesylation of the primary hydroxyl functionality with concomitant elimination of the tertiary one was followed by reaction with methylamine and protection of the resulting secondary amine to give alkene 122. Ozonolysis of the double bond in 122 and subsequent intramolecular aldol condensation of the resulting ketoaldehyde afforded cycohexenone 123. Rubottom oxidation and acetylation gave 124, which served as substrate in the lipase-... 

Enhancing the utility of the allq lation-rearrangenient sequence in synthesis, the Evans group addressed the problems of a-versus-y alkylation as well as low anion reactivity by employing heterocyclic sulfides as the alleviation substrates tScheme IR.IfiE For instance, allylic imidazolyl sulfide 56 could be allqvlated efficiently, reaction at the a-position being favored by a chelated but reactive allyl lithium intermediate. Oxidation of 57 to the allylic sulfoxide and treatment with a secondary amine thiophile provided allylic alcohol 58 in high yield and with excellent stereoselectivity at the trisubstituted alkene. Allylic oxidation with manganese dioxide completed a synthesis of the sesquiterpene nuciferal (59). ... 

Previously reported bis(amidate)- and tethered-amidate-supported zirconium complexes can be used for alkene hydroamination catalysis, and all substrate scope and mechanistic investigations of these systems are consistent with the [2+2] cycloaddition mechanistic profile [61, 62). However, more recent catalyst systems that can be used with secondary amines show broader substrate scope, similar to that attained by rare earth elements and suggest a mechanistic similarity to that observed for previously intensely investigated rare earth hydroamination catalyst systems [7j. Such complexes are proposed to achieve ring closure via o-bond insertion, and thus, consideration of such a mechanistic profile in this case demanded further investigation. 

More recently, reactivity investigations have explored the scope of reactivity of previously developed catalysts. With respect to advances in group-lO-catalyzed allene hydroamination, Widenhoefer [229] explored Pt(II) neutral and cationic species for the intermolecular hydroamination of allenes with secondary alkylamines to make aUylamine products with excellent regioselectivity and diastereoselectivity (E/Z) (Scheme 15.43). This work builds upon a 2005 report for neutral Pt(II) compleiKs for the intermolecular hydroamination of alkenes with secondary amines [230, 231]. In the 2010 report, a variety of cyclic and acyclic alkylamines can be used as substrates, although neither arylamines nor primary amines are disclosed as substrates. This system is also limited to monosubstituted allenes. Consistent with long-standing proposals [231], outer-sphere addition of the amine to a cationic Pt(II) It-allene complex is proposed [229]. 

Neutral group 4 metal complexes appear to possess a relatively broad scope for catalytic hydroaminations. They have been employed for the intramolecular hydroamination of alkynes [2], allenes [3], and alkenes [4] as well as the inter-molecular hydroaminations of alkynes [5] and allenes [6]. Primary aryl- and alkylamines readily react, but secondary amines have posed a greater challenge for this type of transformation with neutral catalysts [7]. For the reactions of the latter, cationic Zr and Ti complexes have been employed in intramolecular cyclizations of aminoalkenes [8]. Very recent work suggests that substrates that are difficult to hydroaminate may favor hydroaminoalkylations instead (Scheme 13.2) [9]. 

The highly diastereoselective hydroamination catalyzed by 13a/Sc N(SiMe3)2)3 was applied as a key step in a preparation of (zt)-xenovenine (Scheme 8) [100], Xenovenine is also accessible via a bicyclization of an aminoallene-alkene substrate in both racemic and enantiopure form [101]. Both approaches involve hydroamination with a secondary amine, a reaction that often requires a stericaUy more open rare earth metal catalyst [17]. 

Interestingly, the propensity of the boron atom to engage in secondary interactions was also examined by Jacobsen. The interaction of the rhodium complex 60 with a model substrate, namely 5-hexen-l-amine, was monitored by 1H NMR spectroscopy.62 The stronger upheld shifts of the alkene resonances compared to those observed upon coordination of the same substrate to the related boron-free salt [Rh(cod)(DIOP)][ClC>4] (cod = cycloocta-1,5-diene) were attributed to a cooperative behavior of the boron and metal centers of 60 that concomitantly interact with the nitrogen atom and alkene moiety, respectively (Figure 20). 

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