29588-91-8

A unique decarbonylation of an amino acid derivative catalytic system has been established via palladium-catalyzed C-C bond and C-N bond dual activations. By employing 8-aminoquinoline as the directing group, this transformation has been found to facilitate the high chemoselectivity to decarbonylation of amino acid derivatives rather than intramolecular deamination or cross-dehydrogenative coupling reactions. This method provides a straightforward avenue for constructing diverse functionalized amide compounds in good to excellent yields. We proposed a possible reaction pathway that may go through the C-C bond and C-N bond dual activations on the basis of the mechanistic studies.

The regiospecific and stereoselective 1,2-migration reaction of dialkyl α-diazophosphonates for the synthesis of β-amino (E)-enylphosphonates is developed utilizing tetrakis(acetonitrile)copper(I) hexafluorophosphate [Cu(MeCN)4PF6] as the catalyst and N,N-dimethylformamide as an additive. A possible mechanism for the 1,2-migration reaction involving a metal carbene is presented. An investigation on the E/Z isomer selectivity of this process demonstrates that steric factors play an important role on the outcome. This process provides a straightforward access to β-amino (E)-enylphosphonates in moderate to good yields.

A strategy for the construction of spiro[cycloalkane-1,3′-1′λ6-isothiazolidine]-1′,1′,4′-triones through the sulfonylation of 1-aminocyclopropane- and 1-aminocyclobutanecarboxylates with methanesulfonyl chloride followed by alkylation with methyl iodide and subsequent cyclization in the presence of potassium tert-butoxide in N,N-dimethylformamide is reported. An efficient synthesis of starting 1-aminocyclopropane- and 1-aminocyclobutanecarboxylic acids was developed. The reaction of spiro[cycloalkane-1,3′-1′λ6-isothiazolidine]-1′,1′,4′-triones with N,N-dimethylformamide dimethyl acetal (DMF-DMA) gives 5′-[(Z)-(dimethylamino)methylene]spiro[cycloalkane-1,3′-1′λ6-isothiazolidine]-1′,1′,4′-triones, the structure of which was confirmed by X-ray diffraction study.

Abstract The trifluoroborane-catalyzed C-H functionalization/S-H insertion reaction of α-diazophosphonates with thiols has been developed. A plausible reaction mechanism has been proposed to understand the combined reaction. This process provides straightforward access to N,S-acetals containing quaternary centers in moderate to good yields and chemoselectivity.

The asymmetric synthesis of a novel (S)-isocoumarin has been attempted in a single step by the coupling of homophthalic acid with (S)-N-protected amino acids and α-chloroacids at high temperature by exploiting a chiral pool methodology. The coupling of homophthalic acid with N-protected (S)-amino acids gave exclusion of the carboxyl/alkyl group. However, coupling of homophthalic acid with α-chloroacids afforded asymmetric isocoumarins in high yield.

A series of dialkyl a-diazophosphonates has been prepared from natural amino acids. The diazo decomposition of these diazophosphonate compounds with tetrakis(acetonitrile)copper(I) hexafluorophosphate/iodine, [Cu(MeCN) 4]PF6/I2, as catalyst has been investigated. It was found that the diazo decomposition of dialkyl a-diazophosphonates gave a mixture of β,γ-dihydrogen shift and 1,2-hydride migration products and afforded β-alk- enyl-substituted β-amino phosphonates with the Z configuration. The mechanism of this novel diazo decomposition process was discussed.

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Enantiomerically pure vinylglycine (4b) can be prepared from natural ("chiral pool") amino acids by photoelimination of γ-functionalized N-phthaloyl amino acid esters.Two routes have been developed: (a) a three-step synthesis of substrate 3b from (S)-methionine and subsequent photolysis, (b) the use of N-phthaloyl activated methyl 2-amino-4-chloro- or -4-bromo-butanoates 3d,e which are available from (S)-methionine (four-step synthesis) or from (S)-homoserine (two-step synthesis).The photoelimination (of HOSMe from 3b and of HX from 3d,e) proceeds quantitatively and leads to N,C-protected vinylglycine 4a in high yields.This strategy could also be applied to peptide-bound substrates as was shown for the protected Met-Gly (5b) which was transformed into the N-protected vinylglycineglycine dipeptide 6 in three steps. - Keywords: Vinylglycine; Photoelimination; Norrish-II photoreaction; Dipeptide; Peptide modification, photochemical

Methionine is converted into the N,O-protected derivative 1b. Chlorination of 1b with sulfuryl chloride results in a mixture of the α-halosulfides 2a and 2b in the ratio of 6:1. Hydrolysis of 2a gives the title compound 3 in 64% yield.

The N-phthaloyl-α-amino acid methyl esters of 2-aminobutyric acid (2a), valine (2b), norvaline (2c), tert-leucine (2d), isoleucine (2e), allo-isoleucine (2f), leucine (2g), methionine (2h), alanine (2i), and phenylalanine (2k) were synthesized in enantiomerically pure form via the N-phthaloyl-α-amino acids (1a-k), and their photochemistry was studied.Except 2i and 2k, which proved to be photostable, all compounds were converted into three types of products, depending on the substitution pattern: a) isomerization products (derivatives of β,γ-unsaturated α-amino acids) 3a, b, c, and e, b) ring expansion products (benzazepinedione esters) 4a and c, and c) cyclization products (5d from the tert-leucine derivative 2d).High diastereoselectivities (d.r. >95:5) were observed for all reactions except the transformations of the 2-aminobutyric acid derivative 2a.The absolute configuration of the α-stereogenic center was retained during photolysis, as proven for the isodehydrovaline (type a product) 3b.PCC oxidation (to give 7b) and hydrogenation afforded 2b with an optical rotation comparable to the starting material.Treatment of 3b with an acid or a base led to epimerization (3b') or isomerization of the C=C bond (6b), respectively.The diastereomeric dihydrobenzazepinedione esters 4a, b were formed with d.r. = 33:67 (cis:trans) and in 60percent yield during photolysis of 2a.The isoleucine derivative 2e, however, was converted into the cis isomer 4a with high diastereoselectivity (d.r. >95:5), whereas the corresponding allo substrate 2f was only converted into the trans-isomer 4b.Ethylene was extruded during irradiation of the latter substrates and during irradiation of the norvaline derivative 2c, whereas propene extrusion from the leucine derivative 2g led to the formation of the unsubstituted type b product 4c.The methionine derivative 1h was the only N-phthaloylamino acid which did not show photodecarboxylation, instead two ξ-hydrogen abstraction products were formed: the hydroxy acid 9h and the tetracylic lactone 10h.The methionine ester 2h was only converted into the ring expansion products 11h, h' presumably by a photo electron transfer step.The chronology of the double hydrogen transfer reaction (γ- followed by δ-H abstraction, leading to type a products) was determined by using the deuterium labeled compound (+/-)-2b.Key Words: Photochemistry / α-Amino acids / Amino acids, β,γ-unsaturated / Photoisomerization / Benzazepinedione esters / Selectivity, enantio-, diastereo-