Amino-allenes

Scheme 2.20 Palladium(0)-catalyzed aziridination of a-amino allene 66.

Steiically congested cw-aziridines such as 137 were prepared from the deiivatized amino allyl alcohol precursor 136 through a palladium-catalyzed cyclization reaction <99TL1331>. This methodology has also been extended to the cyclization of amino allenes <99JOC2992>. 

A few synthetic applications of palladium catalysis appeared this year. The palladium-catalyzed cyclization of amino allenes 58 occurs with coupling of aryl iodides or vinyl triflates at the 3-position <990L717, 99SL324>. The cyclization can also proceed by the exo-trig pathway, but under suitable reaction conditions the piperidine 59 is prepared selectively. The intramolecular cyclization of amines onto N-allylbenzotriazoles similarly affords piperidines <99JOC6066>. 

Scheme 61 Preparation of tricyclic P-lactam 175 using amino-allene cyclization (i) TsNCO, THF, RT (ii) Pd (OAc)2 10 mol%, LiBr, Cu (OAc)2, k2co3, o2,...

Amino allenes of type 58 can be prepared by palladium-catalyzed reduction 57 [39]. 

Scheme 19. Palladium-catalyzed reduction of amino allenes 58. Mts = 2,4,6-trimethylbenzenesulfonyl.

Intramolecular carbonylative carboamination of unsaturated amines, converted in the presence of palladium catalysts and carbon monoxide, gives nitrogen heterocycles9-10. Medium to low E Z stereoselectivities have been reported for conversions of this type using amino allenes 211 or similar systems26. 

Me2SiCl give exclusively Me3SiCH2C=C—NEt2, a 2 1 mixture of the latter compound and H2C=C=C(SiMe3)NEt2 is produced in the silylation of the potassium compound. In the case of the lithiated c//rae//iy/amino allene equal amounts of the silylated allene and acetylene are obtained [9]. 

Inuki S, Oishi S, Fujii N, Ohno H (2008) Total Synthesis of ( )-Lysergic Acid, Lysergol, and Isolysergol by Palladium-catalyzed Domino Cyclization of Amino Allenes Bearing a Bromoindolyl Group. Org Lett 10 5239... 

While effective bimetallic catalyst design has the potential to lead to an enhancement of the reaction rate, the use of chiral bimetallic catalysts has also been explored to enhance the enantioselectivity of a reaction. Such bimetallic chiral induction is excellently demonstrated by the use of digold catalysts for the hydroamination of prochiral substrates such as allenes and alkenes [59]. The bimetallic Au catalyst 66, for example, was shown to be an effective catalyst for the hydroamination of amino-allenes in the presence of a silver salt activator (Scheme 24) [106]. The highest enantioselective induction for this reaction was achieved with a 1 1 ratio of AgBp4 to 66 (51 % ee) suggesting that the monocationic... 

Scheme 24 Different reactivities and selectivities of chiral bimetallic Au complexes used in the enantioselective hydroamination reaction of amino-allenes...

Yudin and coworkers reported a palladium-catalyzed synthesis of multisubstituted pyridines from amino allenes, aldehydes, and aryl iodides in 2013 [124], Moderate to good yields of the desired pyridines were prepared from readily available building blocks (Scheme 3.62). 

Step 1 To an oven-dried small vial containing a solution of a-amino allene (1.0 mmol) in anhydrous DCM (2mL) was added anhydrous MgS04 (100 mg) and aldehyde (1.0 mmol). The reaction was stirred at room temperature for approximately 5—8 h, at which point the complete conversion of starting material to imine was confirmed by crude NMR. The resulting mixtrue was filtered through celite and concentrated to obtain the skipped allenyl imine as an orange oil which was carried over to the next step without further purification. 

Azetidines are compounds of interest in the field of agricultural and pharmaceutical chemistry. They are also useful as monomers and cross-linkers in polymer industry. Due to ring strain associated with it, azetidines are also useful S5mthons in organic chemistry. The common methods for S5mthesis of azetidines are cyclizations of y-amino alcohols, y-amino halides, 3-amino allenes, reactions of 1,3-dielectrophiles with amines, metal-catalyzed cyclizations in diazocarbonyls, cycloaddition reactions, and reduction of 2-azetidinones. There are several reports in literature on the S5mthesis of azetidines in aqueous media. A diastereoselective synthesis of azetidines is reported by the reaction of azazirconacyclopentane derivatives with iodine followed by treatment with aqueous potassium carbonate [26]. 

Asymmetric hydroamination has made a significant contribution toward the synthesis of chiral cyclic amines. Intramolecular asymmetric hydroamination of amino alkenes, amino alkynes, and amino allenes has been extensively studied to develop interesting strategies for the synthesis of chiral cyclic amines. 

Along with amino alkenes, other substrates like amino-allenes and amino-alkynes have also served as useful... 

It has been proposed that Au-catalyzed asymmetric hydroamination/cyclization of amino-allenes proceeds through a catalytic cycle demonstrated in Scheme 39.3. The chiral Au-complex activates the allenes generating the complex A, which is attacked by nitrogen to form species B. Species B upon protonolysis releases the product and regenerates the catalyst. 

SCHEME 39.3. Mechanism of hydroamination/cyclization of amino-allenes with Au-complexes. ... 

Similar to amino-alkenes 1, amino-allenes 4 could also be smoothly converted into the corresponding cyclized product under the same reaction condition (Scheme 39.5). 

SCHEME 39.5. Chiral Br0nsted-acid-catalyzed synthesis of heterocycles from amino-allenes. ... 

To meet the demand, the compound has been successfully synthesized by hydroamination/ cyclization of amino-allene 13" ° (Scheme 39.7). Enantio-selective addition of n-dibutyl zinc to allenyl aldehyde 10 using a chiral Ti catalyst (generated by heating the mixture of 11 and Ti(Ot-Pr)4 in dry toluene at 40-45 °C for 30 minutes) provides the corresponding hydroxyl... 

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