Rhone-poulenc Rorer S.a.

Denis Largeau

Patrick Leon

Michael O'Brien

Thierry Durand

Matthew Powers

Ching Tsuei

Novel derivatives of 1R- or 1S-2-azabicyclo�2.2.1!heptane with the general formula (I) or (I'), preparation and their application. ##STR1## In the general formulas (I) and (I'), R represents a hydrogen atom or a group with the formula ##STR2## respectively, in which R.sub.1 represents an alkyl group containing 1-4 carbon atoms and Ar represents an optionally substituted phenyl or a- or b-naphthyl group.

Derivatives of 2-azabicyclo�2.2.1! heptane, their preparation and their

A method for the preparation of a lactam compound of formula ##STR1## wherein R'.sub.1 and R'.sub.1 independently are acyl or aroyl, or taken together form an optionally substituted methylene, and G.sub.1 is hydrogen or an amino protecting group, comprising oxidizing a bis O-protected 1R-2-azadihydroxybicyclo-�2.2.1!heptane compound of formula ##STR2## with about 0.1 mol % to about 1 mol % of RuO.sub.2 or hydrate thereof in the presence of about 3 equivalents of an oxidant to form the lactam compound with an enantiomeric excess of greater than or equal to about 95%.

L-tartaric acid salt of a (1R) diastereomer of a

A method for the preparation of a compound of formula ##STR1## wherein R is hydrogen or, respectively, a group of formula ##STR2## R.sub.1 is alkyl; Ar is optionally substituted aryl; and

A compound of formula ##STR1## wherein R is a group of formula ##STR2## R.sub.1 is alkyl; and Ar is optionally substituted aryl.

A method according to the invention is directed to the preparation of a 2-azadihydroxybicyclo�2.2.1!heptane compound of formula ##STR1## wherein * represents an R chirality, *' represents an S chirality, R is hydrogen or, respectively, a group of formula ##STR2## wherein R.sub.1 is alkyl and Ar is optionally substituted aryl, comprising bishydroxylating a bicyclo�2.2.1!heptene compound of formula ##STR3## wherein *, *' and R are as previously defined, in the presence of about 0.1 mol to about 5 mol % of a metal osmate compound or about 0.06 mol % to about 0.07 mol % osmium tetroxide, and an oxidizing agent capable of regenerating osmium tetroxide. The invention is also directed to the treatment of the (1R) diastereomer of the 2-azadihydroxybicyclo�2.2.1!heptane compound (I) wherein R is a group of formula II with L-tartaric acid, and the L-tartaric acid salt product thereof. Furthermore, the invention is directed to using the (1R) diastereomer of the 2-azadihydroxybicyclo�2.2.1!heptane compound in an acid facilitated acetalizing or ketalizing reaction that results in the protection of the dihydroxy moieties thereof in isopropanol. In addition, the invention is directed to oxidizing a bis O-protected derivative of the (1R) diastereomer of the 2-azadihydroxybicyclo�2.2.1!heptane compound to a corresponding lactam compound in the presence of about 0.01 mol % to about 1 mol % of RuO.sub.2 with about 3 equivalents of an oxidant to form the lactam compound with in an enantiomeric excess ('ee') of greater than or equal to about 95%.

Novel derivatives of 1R- or 1S-2-azabicyclo�2.2.1!heptane with the general formula (I) or (I'), their preparation and their application. ##STR1## In the general formulas (I) and (I'), R represents a hydrogen atom or a group with the formula ##STR2## respectively, in which R.sub.1 represents an alkyl group containing 1-4 carbon atoms and Ar represents an optionally substituted phenyl or .alpha.- or .beta.-naphthyl group. The novel products with the general formula (I) are particularly useful for the preparation of adenosine agonists.

Derivatives of 2-azabicyclo�2.2.1!heptane, their preparation and their

Novel derivatives of 1R- or 1S-2-azabicyclo[2.2.1]heptane with the general formula (I) or (I'), their preparation and their application; ##STR1##

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Taluyers, France

Denis Largeau