A simple protocol was introduced to prepare several enantiomerically pure heterocycles by using (–)‐(1R,2R,3S,4S)‐3‐aminonorbornene‐2‐carboxylic acid as a chiral auxiliary. The protocol is based on a domino ring‐closure reaction, in which the relative configuration of the new asymmetric center is controlled by the stereochemistry of the amino acid, followed by a microwave‐induced retro‐Diels–Alder reaction.

Diastereomers of tetracyclic pyrrolopyrimidine derivatives 2 and 3 were prepared in a three-step domino reaction from diexo-3-aminobicyclo[2.2.1]hept-5-ene-2-carboxamide with levulinic acid or p-toluoylpropionic acid. When subjected to a microwave-mediated retro-Diels-Alder reaction, these tetracycles furnished bicyclic pyrrolo[1,2-a]pyrimidines through the loss of cyclopentadiene.When enantiomeric diexo-3-aminobicyclo[2.2.1]hept-5-ene-2-carboxamide was used, the products were enantiomeric heterocycles with ee >99%, demonstrating that the title compound is an excellent chiral source.Cyclic b-amino acids have attracted great interest in the past decade, and this has become a hot topic in synthetic and medicinal chemistry. These compounds can be widely applied as building blocks in peptide chemistry, in drug research, and in heterocyclic and combinatorial chemistry. [1][2][3][4][5] A new application of diendo-and diexo-3-aminobicyclo[2.2.1]hept-5-ene-2-carboxylic acid (diendo-or diexoaminonorbornenecarboxylic acid) and their derivatives was discovered by Stájer and coworkers: the construction of saturated heterocycles based on them and the subsequent removal of cyclopentadiene in a mild thermal process. This is a new strategy for the preparation of monoand bicyclic heterocycles (A major goal of synthetic organic chemistry is the asymmetric synthesis of biologically active compounds, and especially heterocycles. The use of chirality transfer is a powerful method to generate new stereogenic centers. 9,10 Our present aim was to investigate the applicability of diexo-3-aminonorbornane-2-carboxylic acid enantiomers as chiral sources for the synthesis of several simple heterocycles. The most important elements of the strategy are: i) synthesis of a heterocycle from a b-amino acid or its derivative by generating a new asymmetric center(s); ii) separation of the diastereomers, if necessary; iii) removal of the cyclopentadiene in an RDA reaction. In diastereoselective reactions, the starting amino acid controls the new stereogenic center(s) and the chirality of the amino acid is transferred to the heterocycles. Since determination of the relative configuration of the intermediate heterocycles is generally a routine process, the absolute configuration of the final product will also be evident.Scheme 1 Synthesis of bicycles 4 by domino ring closure, followed by retro-Diels-Alder reaction Racemic diexo-3-aminobicyclo[2.2.1]hept-5-ene-2-carboxamide (rac-1) was prepared by known literature protocols. Bicyclo[2.2.1]hepta-2,5-diene underwent the 1,2-dipolar cycloaddition of chlorosulfonyl isocyanate 11 to give the corresponding b-lactam, which was ring-opened to afforded the amino acid ethyl ester with 20% ethanolic HCl, and then amidated with methanolic ammonia. 12 The enantiomeric (-)-1 carboxamide was prepared from the racemic lactam, which was selectively ring-opened to the amino acid with water in the presence of Lipolase in diisopropyl ether at 70 °C. 13 Opening of the enantiomerically O COOH R PTSA toluene reflux, 10 h ra...

An extremely convenient, environmentally benign spirocyclization under either aqueous or solventless conditions, developed for the preparation of spiro[cyclohexane-1,2Ј-(1ЈH)-quinazolin]-4Ј(3ЈH)-one (3), has been utilized to convert α-and β-aminocarboxamides 5a, 5b, 6a-c and 9 and cycloalkanones 2-2b and alkanones 2c-e into 1,4-diazaspiro-[4.5]decan-2-one (10) and cis-, diexo-or diendo-2,2Ј-disub-

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(Di-exo-3-amino-7-oxabicyclo[2.2.1]hept-5-en-2-yl)methanol (3) was treated with oxo carboxylic acids [p-toluoylpropionic acid, cis-or trans-(p-toluoyl)cyclohexanecarboxylic acid, -benzoic acid or methanobenzocyclooctenecarboxylic acid] to furnish the oxanorbornene-fused pyrrolo [1,3]oxazine 4, the isoindolo[1,3]oxazines 5 and 6, and the methanobenzocyclooctenepyrrolo [1,3]oxazine 10, together with the retroDiels−Alder products pyrrolooxazinone 7, oxazinoisoindo-