Azaspiro

There are only few reactions known introducing substituents to the H-bearing nitrogen of oxaziridines. (V-Alkylation of l-oxa-2-azaspiro[2.5]octane (3,3-pentamethylene-oxaziridine 52) with r-butyl chloride to give (53) was carried out for structure proof of (52). This reaction is of no preparative importance, since N-alkylated oxaziridines are easily obtained by ring synthesis. 

The marked tendency of l-oxa-2-azaspiro[2.5]octane (52) to transfer its NH group gives rise to smooth reactions with sulfur compounds. Aminothiocyanate (94) is formed in 91% yield at room temperature within one minute and 4-methylbenzenesulfonamide (95) is formed within five minutes in 84% yield from the sulfinate (68TH50800). 

Azaspiro[2.2]pent-1 -ene, 2-phenyl-irradiation, 7, 63-64 1,2-Azastannete nomenclature, 1, 12... 

Oxa-2-azaspiro[2.5]octane A7-alkylation, 7, 204 hydrogen abstraction, 7, 26 NH-transfer, 7, 209... 

The solid state structure of (3>S,8 Sj-10-(8-amino-6-azaspiro[3,4]octan-6-yl)-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7//-pyrido[l,2,3-dfe]-l,4-benzoxa-zine-6-carboxylic acid (218) was determined by X-ray diffraction study (98CPB1710). The structure of 6,10-dihydropyrido[2,l-c][l,4]benzoxazine-6,10-dione 219 was established by X-ray diffraction analysis. It contains a crystal solvate with /j-xylene (99MI40). 

Also. 77/-pyrrolo[l,2-fl]azepin-7-ones, e.g. 22, available by the thermal rearrangement of 1-azaspiro[4.5]dcca-l,3,6,9-tetraen-8-ones 21, in trifluoroacetic acid form the deep-blue 7-hy-droxypyrrolo[l,2-tf]azepinium cations, e.g. 23.219 In hot 48 % hydrobromic acid, however, the spiro compound 21 is re-formed. 

CN 8-[4-[4-(2-pyrimidinyl)-1 -piperazinyl]butyl]-8-azaspiro[4.5]decane-7,9-dione monohydrochloride... 

CN [85-[7[R (R )],8/ ]]-7-[2-[[l-(ethoxycarbonyl)-3-phenylpropyl]amino]-l-oxopropyl]-l,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid... 

ChH, N20 1659-31-0) see Paclitaxel l-(2 (i-dipyrrolidino-4-pyrimidinyl)pipera7jne (C f,H2(iN(5 111641-17-9) see Tirilazad mesilate S)-l, 4-dithia-7-azaspiro[4.4)nonane-S carboxylic acid hydrobromide... 

A common procedure in C-C-bond formation is the aldol addition of enolates derived from carboxylic acid derivatives with aldehydes to provide the anion of the [5-hydroxy carboxylic acid derivative. If one starts with an activated acid derivative, the formation of a [Mac lone can follow. This procedure has been used by the group of Taylor [137] for the first synthesis of the l-oxo-2-oxa-5-azaspiro[3.4]octane framework. Schick and coworkers have utilized the method for their assembly of key intermediates for the preparation of enzyme inhibitors of the tetrahydrolipstatin and tetrahydroesterastin type [138]. Romo and coworkers used a Mukaiyama aldol/lac-tonization sequence as a concise and direct route to 3-lactones of type 2-253, starting from different aldehydes 2-251 and readily available thiopyridylsilylketenes 2-252 (Scheme 2.60) [139]. 

Alkaloids Containing an Azaspiro[4.5]decane Ring System Halichlorine... 

For 5-(2-diazo-l,3-dioxobutyl)-l-oxa-5-azaspiro[5,5]undecane (313), intramolecular carbenoid insertion into a (N)C—H bond represents quite an unusual way of constructing a P-laetam ring 285). 

CARBOETHOXY-2,3-DIMETHYL-1-OXA-8-AZASPIRO[4-5]DECANE, a procedure that exemplifies a new stereocontrolled method for constructing substituted tetrahydrofurans. 

A. Preparation of (2R,3S)- ana (2S,3S)-1,4-dioxa-2,3-dimethyl-2-(1-methyl-ethenyl)-8-carbcethoxy-8-azaspiro[4.5]decane. An oven-dried, 500-mL, three-necked, round-bottomed flask is fitted with a mechanical stirrer, 100-mL addition funnel, and rubber septum, and then is charged with 100 mL of dry tetrahydrofuran (Note 1) and... 

Stereochemical control of intramolecular 1,3-dipolar cycloadditions by route b (Scheme 2.211) was realized in the asymmetric synthesis of l-azaspiro[4.5] decanes by using the chiral (2R)-bomane-10,2-sultam (X ) auxiliary in the dipo-larophilic fragment (Scheme 2.220) (718). 

Diastereoselective 1,4- and 1,6-addition reactions of lithium amides to chiral naph-thyloxazolines were used by Shimano and Meyers108-110 for the synthesis of novel amino acids. For example, treatment of (S )-2-(l-naphthyl)-4-t-butyloxazoline with lithi-ated l,4-dioxa-8-azaspiro[4.5]decane and iodomethane provided the diastereomerically pure 1,4-addition product with excellent yield cleavage of the heterocyclic rings then gave the desired /3-amino acid (>99% ee/ds equation 32)108,109. In contrast to this, most acyclic lithium amides reacted with these oxazolines under 1,6-addition the products were transformed smoothly to 5-amino acid derivatives (equation 33)110. 

Heteroatom Oxidation, Dehydrogenation Electrooxidative kinetic resolution of rac alcohols mediated with a catalytic amount of an optically active A-oxyl was performed in an undivided cell at constant current conditions. A high enantiomeric purity for the recovered alcohol was found, which could be increased by electrolysis at lower temperatures. The optically active A-oxyl was recovered and used repeatedly without change in efficiency and selectivity [368]. Cyclovoltammetry with the A-oxyl (GR, 7S, 10/f)-4-oxo-2,2,7-trimethyl-10-isopropyl-l-azaspiro[5.5]undecane-A-oxyl as catalyst showed for rac-1-phenylethanol a highly enhanced catalytic... 

The 2-azaspiro[5.5]undecane group of alkaloids occur in certain plants of the genus Nitraria. There has been some interest in the biological activity of these alkaloids because their structures are similar to the histrionicotoxins, a group of... 

The total number of atoms in the azaspirocycle is optimally seven or eight, similar to the optimal requirements in the monocyclic guanethidine series. However, an additional factor with the azaspiro-alkanes is that the number of atoms in the heterocyclic ring should be as large as possible consistent with the previous condition. Compound (XXX) has a longer duration of action than guanethidine both in animals [221] and in man [224]. 

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