Robert S. Atkinson

Aziridination by oxidative addition of N-aminoquinazolones to alkenes: Evidence for non-involvement of N-nitrenes

Abstract Oxidation of 3-aminoquinazolones e.g. (22) with lead tetra-acetate at −20°C gives N -acetoxyaminoquinazolones e.g. (23) which are stable in solution at this temperature. These N -acetoxyaminoquinazolones function as inter- and intramolecular aziridinating agents for alkenes and appear to be playing the role previously ascribed to the corresponding N -nitrenes. An analogous N -acetoxyaminophthalimide intermediate (31) is implicated in the lead tetra-acetate oxidation of N -aminophthalimide (4).

Amination with 3-acetoxyaminoquinazolin-4-(3h)ones: preparation of α-aminoacid esters by reaction with silyl ketene acetals followed by NN bond cleavage

Abstract Solutions of 3-acetoxyaminoquinazolinone (5) react with enol ethers and silyl ketene acetals to give α-aminoaldehyde α-aminoketone or α-aminoacid derivatives. Acylation of the exocyclic nitrogen in these derivatives, as a preliminary to reductive N  N bond cleavage, could only be accomplished by indirect means. Samarium diiodide, however, effected the reduction of this N  N bond without the necessity for N -acylation. Solutions of the corresponding enantiopure 3-acetoxyaminoquinazolinone (34) brought about the diastereoselective amination of the prochiral silyl ketene acetal (15) and reductive N  N bond cleavage of the major diastereoisomer lead to enantiopure 2-phenylalanine methyl ester.

3-(N,N-Diacylamino)quinazolin-4(3H)-ones as enantioselective acylating agents for amines

Abstract The presence of an N–N chiral axis in a 3-( N -benzoyl- N -isobutanoyl)aminoquinazolin-4(3 H )-one (DAQ) bearing a chiral substituent in the 2-position of the quinazolinone allows separation of two enantiopure diastereoisomers; one of these diastereoisomers reacts with racemic 2-methylpiperidine to give ( R )(+)-1-benzoyl-2-methylpiperidine (95% ee) and ( S )-2-methylpiperidine (91% ee) even using stoichiometric quantities of reagents (1 equiv. DAQ: 2 equiv. amine).

Aziridine-azirine transformation by 1,2-elimination via an aziridinyl carbanion intermediate

Abstract Desilylation of aziridine (5) by treatment with cesium fluoride in dry dimethylformamide in the presence of benzaldehyde followed by oxidation with manganese dioxide gives the benzoylaziridine (11) in 80% yield: in the absence of benzaldehyde, the presumed aziridinyl carbanion intermediate (9) gives the aziridine (7) (58%).

REAGENT-CONTROLLED DIASTEREOSELECTIVITY IN AZIRIDINATION OF ALKENES BY CHIRAL 3-ACETOXYAMINO-3,4-DIHYDROQUINAZOLIN-4-ONES 1'-(T-BUTYLDIMETHYLSILYLOXY )ETHYL AS THE CHIRAL 2-SUBSTITUENT ON THE QUINAZOLINONE

Abstract Conformational preferences within the t BuMe 2 SiOCH(Me)CN unit in 3-acetoxyaminoquinazolinone 3 lead to well defined site preferences for H, Me and OSiMe 2 t Bu in the transition state for, and hence high diastereoselectivity in, its reaction with β-trimethylsilylstyrene 4 to give aziridine 5 .

AZIRIDINATION OF ELECTRON-RICH ACYCLIC ALLYLIC ALCOHOLS USING 3-ACETOXYAMINOQUINAZOLINONES

Abstract The products from aziridination of the phenyl-substituted allylic alcohols 6 and 7 with 3-acetoxyaminoquinazolinones 1 and 15 have been compared with those from aziridination of the methyl ester analogues 2 , and 3 : the differences in diastereoselectivities using these electron-rich and electron-deficient alkenes are ascribed to the intervention of transition states 8 and 4 respectively.

Completely diastereoselective aziridination of α,β-unsaturated acids via intramolecular reaction of 3-acetoxyaminoquinazolin-4(3H)-ones

(R)-3-Amino-2-[1-(2-hydroxyethoxy)ethyl]quinazolin-4(3H)-one 10 was prepared in 62% yield without the need for chromatography and O-cinnamoylated; reaction with lead tetra-acetate gave aziridine 12 as a single diastereoisomer in quantitative yield which was converted into the β-amino acid ester 15 corresponding to overall enantioselective addition of ammonia to the double bond of cinnamic acid.

Ring-opening of chiral N-(3,4-dihydro-4-oxoquinazolin-3-yl)-substituted aziridines (Q∗-substituted aziridines): access to Q∗-free chirons

Abstract The presence of the quinazolin-4(3H)-one ring (Q∗) in N-(Q∗)-aziridines facilitates ring-opening by nucleophiles: removal of the Q∗ group from enantiopure ring-opened products gives useful chirons.

Acid-catalysed ring-opening of N-(3, 4-dihydro-4-oxoquinazolin-3-yl)-substituted aziridines: aziridine ring-opening with retention of configuration

Abstract The presence of the quinazolin-4(3H)-one (Q) ring in 1-(Q)-2-vinylaziridine (2) can be used to control the stereochemistry of the 3-membered ring-opening; participation by the quinazolinone carbonyl oxygen brings about ring-opening with retention of configuration.

Reactions of cyclic β-keto esters and other enol derivatives with 3-acetoxyamino-2-isopropylquinazolin-4(3H)-one: further oxidation of the cyclic α-(3,4-dihydro-2-isopropyl-4-oxoquinazolin-3-yl)amino ketones with lead tetraacetate leading to ring-expansion (in dichloromethane) and ring-cleavage (in methanol)

The cyclic β-keto esters 12, 20, 22, 26, the β-diketone 28 and the enol silyl ethers 24 and 30 have been converted in 60–77% yields into the corresponding α-(oxoquinazolinyl)amino cyclic ketone derivatives 16, 21, 23, 29, 27, 25 and 31, respectively, by reaction with 3-acetoxyamino-2-isopropylquinazolin-4(3H)-one 11. Further oxidation of some of these products with lead tetraacetate gives products whose nature depends on the solvent used; in dichloromethane, 16, 21 and 25, which contain 5-membered ring ketones, give ring-expanded products 32, 38 and 39, respectively whereas, in methanol, ring-cleavage of 16, 25 and 27 occurs to give imino-esters 41, 44 and 42/43, respectively. Ring-expansion of 23, 27 and 31, which contain 6-membered ring ketones, does not occur and the only isolated product in each case is the benzoxazinone 40. A mechanism which accounts for this dependence on the solvent is presented: radical intermediates do not appear to be implicated.