Hydroamination carbamates

In order to find a suitable catalyst for intermolecular hydroaminations of 1,3-dienes, several metal sources were screened for the reaction of diene la (4 equiv) with carbamate 2a, and Bi(OTf)3 gave promising results [21, 22], The optimization studies using Bi(OTf)3 are summarized in Table 1 and show that 10 mol% of... 

Table 2 Bi(OTf)3/Cu(CH3CN)4PF6/dppe-catalyzed intermolecular hydroamination of la with various carbamates, sulfonamides, and carboxamides...

Table 5 Intermolecular hydroamination of various 1,3-dienes with carbamate 2d...

Hydroamination of Alkenes Kobayashi et at. found that several transition metal salts displayed high catalytic activity in aza-Michael reactions of enones with carbamates, while conventional Lewis acids (BF3-OEt2, A1C13, TiCl4...) were much less active. 

Ph3PAuOTf has been shown to catalyse intra- and inter-molecular hydroamination of unactivated alkenes with sulfonamides in a Markovnikov fashion.115 The same complex catalyses hydroamination of 1,3-dienes with carbamates (e.g. PhCH2OCONH2) and sulfonamides at room temperature.116 An intramolecular version of the hydroamination with the Cbz group (benzyloxycarbonyl) has also been reported. The latter... 

The enantioselective hydroaminations of allenes with chiral phosphine catalysts was accomplished with substrates that had a terminal symmetric substitution and with the amines protected as carbamates or sulfonamides. The same symmetric substituents were necessary for the enantioselective transformation nsing chiral counterions. However, very recently, high enantiomeric excesses were reached with trisubstituted asymmetric allenes by a dynamic kinetic enantioselective hydroamination of allenyl carbamates (eqnation 110), even thongh the E/Z ratio of the prodncts was not optimal. 

Hydroamination of olefins is also possible with gold catalysts. In this reaction, the attack comes Ifom a nitrogen nucleophile as a carbamate,a urea, an amide, or a sulfonamide. In the latter case, the reaction can be carried out intermolecularly. While the carbamates, ureas, and amides give only products of intramolecular anunations, the sulfonamides can perform the intermolecular addition. Only the addition of ureas (equation 146) takes place at room temperature, and in the rest of the additions heating is required. The catalysts of choice in all these reactions are cationic gold(I)-species stabilized by phosphines or NHC ligands. The reaction times have been reduced by the use of microwave irradiation. The mechanism of the hydroamination reaction has been studied in detail theoretically. ... 

The intermolecular addition of carbamates to 1,3-dienes (equation 147) under mild conditions has been described as well. The hydrothiolation of 1,3-dienes has also been reported. " Other related conjugate additions can be performed over methylenecyclopropanes (equation 148) with sulfonamides and the resulting product cyclizes by a second hydroamination of an olefin, finally yielding cyclic sulfonamides. This behavior is reproduced in a similar reaction for the ring opening of vinylcyclopropanes with sulfonamides. One more example in this group of reactions is the synthesis of dUiydrobenzofurans from aryl-allyl ethers. ... 

In another variant, A-Boc-hydrazine (i-BuOCONHNH2) is coupled with an aryl halide via the carbamate nitrogen the subsequent Fischer sequence can be conducted in the same pot after addition of acid, with loss of the Boc group. ° Hydroamination of alkynes via various protocols ° also produces arylhydrazones, ready for the Fischer process. 

Hydroamination. Amides, lactams, carbamates and ureas add to 1-alkynes to give enamide derivatives. The stereoselectivity of this anti-Markovnikov addition is sensitive to phosphine ligands that are present. ... 

The use of carbamates as the nucleophile allowed extension of the method to the gold-cataWzed intermolecular hydroamination of conjugated dienes at room temperature. The reaction took place regioselectively as 1,2-addition at the less substituted double bond. 

Representative procedure for the gold-catalyzed intramolecular hydroamination of alkenyl carbamates. Benzyl 2-methyl-4,4-diphenylpyrrolidine-I-carboxylat ... 

Ackermann engineered a copper-catalyzed process to achieve the A-arylation/hydroamination synthesis of indoles (Scheme 4, equation 1) [35], In similar fashion, A-acylindoles and NH-indoles were made available using A-unsubstituted amides and carbamates in place of anilines. In these latter reactions, a vicinal diamine ligand improved the cyclizations. Miura and Hirano reported a... 

One of the best-characterized examples of intramolecular hydroamidation of an alkene with the tethered activated nitrogen of amide and carbamate groups is shown in Equations 16.66a and 16.66b. This reaction is catalyzed by a dicationic palladium complex ligated by a PNP pincer ligand. Like the rhodium-catalyzed hydroamination, this process occurs to form five- and six-membered rings with or without substituents to bias the system toward cyclization.. 

Robinson, R. S., Dovey, M. C. and Gravestock, D. 2005b. Silver-catalyzed hydroamination Synthesis of IV-bridgehead pyrroles, incorporating a protection-deprotection strategy for preparation of cyclic secondary vinylogons carbamates. Eur. J. Org. Chem. 2005 505-511. 

Carbamates are also effective nucleophiles for the gold(I)intramolecular hydroamination of alkynes [12]. For example, treatment of O-propargylic carbamate 10 with a catalytic 1 1 mixture of (PPh3)AuCl and AgOTf in dichloromethane at room temperature led to isolation of 2,5-dihydroisoxazole 11 in 88% yield (Eq. (11.8)). The transformation was effective for alkyl-, alkenyl- and aryl-substituted internal alkynes and terminal alkynes and for N-Boc, Cbz, and Ts derivatives. A similar... 

Widenhoefer and coworkers have reported that the gold(I) phosphine complex [P(t-Bu)2(o-biphenyl)]AuCl is a highly active and selective precatalyst for the intramolecular exo-hydroamination of N-y- and 8-allenyl carbamates [37]. As an example, treatment of the N-6-allenyl carbamate 48 with a catalytic 1 1 mixture of [P(t-Bu)20-biphenyl]AuCl and AgOTf (5mol%) in dioxane at room temperature for 22 h led to isolation of piperidine 49 in 92% yield as a 7.0 1 mixture of cis trans diasteromers (Eq. (11.26)). Gold(I)-catalyzed hydroamination of N-y- and 8-allenyl carbamates tolerated substitution at both the internal and terminal allenyl carbon atoms and the transformation displayed modest selectivity for the transfer of chirality... 

Yamamoto has reported the intramolecular e%o-hydroamination of N-allenyl sulfonamides and carbamates catalyzed by simple, unligated gold(I) and gold(III) salts. Noteworthy was that cyclization of N-allenyl sulfonamide derivatives that possessed an axially chiral allenyl moiety occurred with highly selective transfer of chirality to the newly formed tetrahedral stereogenic carbon atom [38]. For example, treatment of enantiomerically enriched y-allenyl tosylamide 52 (96% ee) with a catalytic amount of AuCl in THF at room temperature led to isolation of ( )-2-(l-heptenyl)pyrroldine ( )-53 in 99% yield with 94% ee (Eq. (11.28)). 

Widenhoefer and Han have reported an effective protocol for the intramolecular hydroamination of unactivated C=C bonds with carbamates [52]. As an example of this protocol, treatment of the N-y-alkenyl carbamate 76 with a catalytic 1 1 mixture of [P(f-Bu)2(o-biphenyl)]AuCl and AgOTf (5 mol%) in dioxane at 60 C for 22 h formed pyrrolidine 77 in 91% isolated yield as a 3.6 1 mixture of diastereomers (Eq. (11.43)). The protocol tolerated substitution at the internal olefinic carbon atom and along the alkyl backbone and the method was applied to the synthesis of both heterobicyclic compounds and piperidine derivatives. This protocol was subsequently expanded to include the intramolecular hydroamination of N-alkenyl carboxamides including 2-allyl aniline derivatives (Eq. (11.44)) [53]. 

In contrast to the hydroamination of alkenes with sulfonamides, the potential of an acid-catalyzed reaction pathway in the hydroamination of alkenes with carboxamide derivatives appears less likely. Hartwig found that the intramolecular hydroamination of alkenes with N-arylcarboxamides was only realized in the presence of stoichiometric amounts of triflic add [50]. In contrast, He reported that triflic add catalyzes the intramolecular hydroamination of an N-4-methyl-4-pentenyl carbamate in toluene at 85 °C [55]. However, in the corresponding gold(I)-catalyzed transformation, the intramolecular hydroamination of an N-4-methyl-4-pentenyl carbamate was markedly slower than was the intramolecular hydroamination of an N-4-pentenyl carbamate [52], which is inconsistent with the antidpated behavior of an acid-catalyzed pathway. Furthermore, control experiments firmly ruled out the presence of an acid-catalyzed reaction pathway in the gold(I)-catalyzed intramolecular hydroamination of alkenes with carboxamide derivates and ureas [53, 54]. 

While the focus of this chapter is on hydroamination with amines, impressive recent advances in the hydroamidation and hydrocarbamation of allenes have been disclosed. Espinet showed that acyclic carbenes can be used as ligands for Au(I) to realize intramolecular hydrocarbamation [240], while Widenhoefer has used the commercially available l,3-bis[(2,6-diisopropylphenyl)imidazole-2-ylidine] (IPr) NHC in combination with cationic Au(I) to realize regioselective intermolecular hydroamination of 1,1-disubstituted allenes with benzyl carbamate to access allylamines with quaternary centers adjacent to N. This same catalyst can also accommodate 1,3-disubstituted allenes and even tetrasubstituted allenes (Table 15.19) [241]. Interestingly, these products are in contrast to the preferred products accessed with related Au(I)-phosphine complexes in combination with aniline substrates (Table 15.18) [239]. Hydroureation has been achieved intramolecularly [242, 243] and will be later discussed (Section 15.3.6). 

Late Transition Metal Catalysts 11191 Table 15.19 Au-NHC-catalyzed allene hydroamination of carbamates. 

Key contributions in the development of late transition metal catalysts toward alkene hydroamination, which precede the 2008 comprehensive review [10], focus on contributions using group 9 and 10 metals. Preferred substrates for these transformations include aminoalkenes [230] for intramolecular reactivity or the use of activated alkenes such as styrene [93, 109, 113, 245] or alkenes substituted with electron-withdrawing substituents to generate hydroamination products via aza-Michael-type reactions [246-249]. Au has also been applied to the hydrofunctionalization of alkenes, although these reactions have demanded the use of protected amine substrates such as ureas [250], tosylamides [251], and carbamates [252]. 

With the assembly of the appropriate alkynyl carbamate, Takemoto has shown that Au(I)-catalyzed hydrocarbamation can be used in a tandem reaction approach to prepare nitidine (Scheme 15.125) [373]. Using the bulkier Buchwald-type mon-odentate biphenyl phosphine ligand, G-endo hydroamination products could be formed preferentially over the 5-exo products. 

Keywords Alkylnyl carbamates, AuC PPha), AgNTf2, ethanol-dichloroethane, room temperature, hydroamination, 1,2-dihydroisoquinolines, 1-alkylydeneyl-l, 2,3,4-tetrahydroisoquinolines... 

Mild and selective 1 1 reactions of amines with 1,3-dienes without telomer-ization are still limited. The recently reported bismuth-catalyzed intermolecular hydroamination with various amides (carbamates, sulfonamides, and carboxamides) to produce allylic amines in good yields is a good example of such a reaction (Equation 56 and Scheme 11.4) [80]. Some additives are necessary to optimize the reaction conditions. Cyclic and acyclic dienes were tested. The isomer ratio (1,2-adduct versus 1,4-adduct) depended on the nature of the dienes. 

Silver(I) salts are often utilized as catalysts for addition reactions. Kozmin and Sun have recently shown that AgNTf2 is a catalyst of choice for the hydroamination of siloxy alkynes with either secondary amides or carbamates to give silyl ketene am-inals [34]. The addition occurs in a syn selective manner, for instance, the reaction of siloxy alkyne (24) with carbamate (25) produces silyl ketene aminal (26) in 86% yield at room temperature under the influence of 1 mol% of AgNTf2 (Scheme 18.9). A six-membered chelated transition state is proposed to explain the high syn selectivity. Diastereoselective bromohydroxylation and bromomethoxylation reactions of cinnamoyl compounds possessing a chiral auxiliary are also effectively promoted by silver(I) salts such as AgNOs [35]. The asymmetric halohydrin reaction has been successfully applied into stereoselective syntheses of (-)-chloramphenicol and (+)-thiamphenicol. Csp-H iodination [36], hydrosilylation of aldehydes [37], and deprotection of TMS-alkynes [38] are also catalyzed by silver (I) salts. 

In the hydroamination of unsaturated carbon-carbon bonds, gold catalysts play an important role. Intermolecular hydroamination of alkenes [177], 1,3-dienes [204], terminal and internal alkynes [205], and allenes [206] are known to proceed smoothly in the presence of PhsP AufI) or AuCls catalyst. In addition, amino olefins also efficiently undergo intramolecular hydroamination using similar gold catalysts. He and coworkers have developed the catalytic cycloaddition of tosylated amino olefins [207], A representative example is shown in Scheme 18.35. When N-tosylated y-amino olefin (97) is exposed to a mixture of PhsP AuCl and AgOTf (5 mol% each) in toluene at 85 °C, pyrrolidine (98) is obtained in 96% yield. The gold(I)-catalyzed intramolecular hydroamination is applicable to N-alkenyl carbamates [208], N-alkenyl carboxamides [209], and N-alkenyl ureas [210], The use of microwave irradiation results in completing the hydroamination in a much shorter time than that required under thermal reaction conditions [211], The... 

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