| In order to synthesize tris(1,3-dihydroxy-2-propyl)amine 1, a precursor to hypervalent nitrogen molecule 2, a new approach to hindered tertiary amines was developed, that is, the insertion of the Rh2(OAc)4-stabilized carbenoid derived from dimethyl diazo-malonate (DDM) into the N-H bond of sterically hindered secondary aliphatic amines. The reaction gave the desired hindered tertiary amines in quite satisfactory yields. For example dimethyl 2-(dicyclohexylamino)propanedioate 45 was formed in 85% yield from dicyclohexylamine, and the severely hindered dimethyl 2-(2,2,6,6-tetramethyl-l-piperidinyl)propanedioate 48 was formed in 38% yield from 2,2,6,6-tetramethyl-piperidine. The Rh2 (OAc)4-DDM reaction was found to work also for arylalkylamines and diarylamines. In these cases, small amounts of products resulting from formal insertion of the carbenoid into an aromatic C-H bond were detected. Substitution at ortho positions caused the yield of C-H insertion products to increase. However, the Rh2(OAc)4-DDM reaction was found not to work for unhindered secondary amines like diallyamine and 2,6-dimethylpiperidine. The carbenoid derived from methyl α-phenyl-diazoacetate 22 was found to insert into the N-H bond of diisopropylamine much faster with higher yield than the carbenoid from DDM. It can also insert into the N-H bond of unhindered secondary amines. Other diazo compounds like 43a performed satisfactorily in Rh2(OAc)4-catalyzed reactions with arylalkylamines and diarylamines, but led to complicated reaction mixtures with dialkylamines.; While investigating N-H insertion of DDM with hexamethyldisilazane (HMDS) in refluxing benzene, the reaction did not afford the desired N-H insertion product. Instead, it led to the bis-σ-homobenzene derivative 5,5,8,8-tetracarbomethoxytricyclo[5.1.0.0 4,6] oct-2-ene, 90, in 58% yield. The one-pot reaction surpasses all previous syntheses of bis-σ-homoaromatics in both ease and efficiency. Other aromatics like naphthalene and anthracene also afford the double cyclopropanation products with Rh2(OAc)4-DDM in 31% and 20% yields respectively. Toluene was found to give a mixture of double cyclo-propanation isomers with one main product 101. The reaction of anisole with Rh2(OAc)4-DDM produced only C-H insertion product in 70% yield. Mild hydrolysis of 90 was selective for the exo esters, giving C2-symmetric tricyclo[5.1.0.04,6]oct-2-ene-5,5,8,8-tetracarboxylic acid endo, endo-dimethyl ester, 108 in 90% yield. The reduction of 90 with LiAlH4 afforded the tetraol 5,5,8,8-tetrakis(hydroxymethyl)tricyclo[5.1.0.0 4,6]oct-2-ene,109, in 73% yield.; Reduction of the dialkylamino diesters available from our studies of N-H insertion afforded amino alcohols in modest to excellent yields. For example, 2-(diisopropylamino) propane-1,3-diol 112 was obtained in 92% yield from 44 and 2-(2,2,6,6-tetramethyl-1-piperidinyl)propan-1,3-diol 116 was obtained in 39% yield from 48. The X-ray analysis of the resulting crystalline amino alcohols revealed that they are more hindered than the most hindered tertiary amine known, triisopropylamine. The cyclic voltammetry studies revealed irreversible oxidation behaviors of most amino alcohols. Compound 114 showed reversible one-electron oxidation potential which correlated well with the hindrance of this amine. Methylation α to the esters of the amino diesters was found to work only for 44 and 45. |
