Asymmetric Diels-Alder and Ficini reactions with alkylidene β-ketoesters catalyzed by chiral ruthenium PNNP complexes: mechanistic insight.

Hydride abstraction from the β-position of the enolato ligand of the previously reported complex [Ru(3a-H)(PNNP)]PF(6) (5a; 3a-H is the enolate of 2-tert-butoxycarbonylcyclopentanone) with (Ph(3)C)PF(6) gives the dicationic complex [Ru(6a)(PNNP)](2+) (7a) as a single diastereoisomer, which contains the unsaturated β-ketoester 2-tert-butoxycarbonyl-2-cyclopenten-1-one (6a) as a chelating ligand. The methyl analogue 2-methoxycarbonylcyclopentanone (3b) gives [Ru(3b-H)(PNNP)]PF(6) as a mixture of noninterconverting diastereoisomers (ester group of 3b trans to P, 5b; or to N, 5c), which were separated by column chromatography. Hydride abstraction from 5b (or 5c) yields diastereomerically pure [Ru(6b)(PNNP)](2+) (7b or 7c).

Application of the lithiation-borylation reaction to the preparation of enantioenriched allylic boron reagents and subsequent in situ conversion into 1,2,4-trisubstituted homoallylic alcohols with complete control over all elements of stereochemistry.

The reactions of Hoppe's lithiated carbamates with vinylboranes and boronic esters give allylic boranes/boronic esters, and subsequent addition of aldehydes provides a new route to enantioenriched homoallylic alcohols with high enantiomeric ratios and diastereomeric ratios. Specifically, reactions of sparteine-complexed lithiated carbamates with trans-alkenyl-9-BBN derivatives followed by addition of aldehydes gave (Z)-anti-homoallylic alcohols in greater than 95:5 er and 99:1 dr. However, in the special case of the methyl-substituted lithiated carbamate, diamine-free conditions were required to achieve high selectivity.

Practical formal total syntheses of the homocamptothecin derivative and anticancer agent diflomotecan via asymmetric acetate aldol additions to pyridine ketone substrates.

Two practical, efficient, and scalable asymmetric routes to DE ring fragment 7, a key building block in the synthesis of the homocamptothecin derivative diflomotecan 4, are described. The "acetal route" starts from 2-chloro-4-cyanopyridine 8 and represents an enantioselective and optimized modification of the original racemic discovery chemistry synthesis. The inefficient optical resolution procedure was replaced by an efficient asymmetric acetate aldol addition (dr 87:13) to a ketone substrate as the key step generating the (R)-configured quaternary stereocenter with high stereoselectivity.

Practical formal total synthesis of (rac)- and (S)-camptothecin.

A practical, efficient and scalable formal total synthesis of (rac)- and (S)-camptothecin is described, which proceeds via the known DE ring building blocks 19 and (S)-19, respectively. The racemic synthesis starts from diethyl oxalate and uses straightforward carbonyl chemistry in order to generate the pyridone ring system. 19 was formed in 8.