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An asymmetric synthesis of the novel nonracemic endothelin receptor antagonists, SB 209670 (1a) and SB 217242 (1b) is described which utilizes an unprecedented asymmetric Nazarovtype ring closure of the alkylidene-1,3-carbonyl compounds. Excellent 1,5-induction is observed which establishes the required S configuration at the C-3 carbon of an indane skeleton.Successful development of a multikilogram scale synthesis of the novel endothelin receptor antagonists, SB 209670 (1a) and SB 217242 (1b) containing three contiguous stereogenic centers, demanded parallel exploratory development of several potentially scaleable routes. 1 Descriptions of several of those routes have already been, and/or, shortly will be disclosed elsewhere. [2][3][4][5][6] In this communication, we summarize the description of an unprecedented asymmetric Nazarov-type ring closure of the alkylidene-1,3-carbonyl compound 3 where excellent 1,5-induction establishes the required S configuration at the C-3' carbon (eq 1). In our most efficient example, an Evan's oxazolidinone chiral auxiliary of S configuration was employed. 7 Equation 1The Nazarov cyclization is an example of a 4p-electrocyclic closure of a pentadienyl cation. As with all pericyclic reactions, the mechanism and stereochemistry on cyclization are inherently related. For 4p-electrolytic cyclization, in addition to the prerequisite stereochemical imperative of conrotatory or disrotatory ring closure, there exists a secondary stereochemical feature that arises because of the duality of allowed electrocyclization pathways. This feature is called torquoselectivity 8-10 and manifests itself when a remote chiral substituent is present, thus, leading to possibilities of diastereoisomers (eq 2 ). Equation 2Shortly after this work was begun, a report by Tietze 11 appeared describing a cyclization to form enantiomerically pure trans-1,2-disubstituted cyclopentanes with three stereogenic centers using chiral malonic acid derivatives. In that report, asymmetric induction was transferred across five carbons, i.e. 1,5-induction. In our results, reported herein, we employ similar conditions on the chiral derivatives 3a-c to form selectively the indanone 4a-c with similar 1,5-asymmetric induction. Scheme 1

A Catalytic Enantioselective Synthesis of the Endothelin Receptor Antagonists SB-209670 and SB-217242. A Base-Catalyzed Stereospecific Formal 1,3-Hydrogen Transfer of a Chiral 3-Arylindenol.-The title antagonists (X) and (XII), containing three contiguous stereocenters, are prepared via a palladium-catalyzed 5-endo-trig cyclization yielding ketone (III). Its enantioselective reduction with the boron catalyst affords alcohol (IV), and as key step a highly stereoselective hydrogen rearrangement of (IV) under optimized conditions gives indanone (V). Further elaboration leads to the desired products. -(CLARK, W. M.; TICKNER-ELDRIDGE, A. M.; HUANG, G. K.; PRIDGEN, L. N.; OLSEN, M. A.; MILLS, R. J.; LANTOS, I.; BAINE, N. H.; J.