Upon activation with (Et 3 O)PF 6 (2 equiv), the ruthenium(II) complex [RuCl 2 (PNNP)] (1; PNNP is (1S,2S)-N,N′-bis(o-(diphenylphosphino)benzylidene)cyclohexane-1,2-diamine) catalyzes the electrophilic fluorination of 1,3-dicarbonyl compounds by N-fluorobenzenesulfonimide (NFSI). Oxygen donors, in particular Et 2 O as cosolvent, increase the activity of the catalyst and, in some cases, the enantioselectivity. The absolute configuration of 2-tert-butoxycarbonyl-2-fluorocyclopentanone (5a), which is obtained with up to 93% ee in catalysis, was determined to be R by derivatization to (1S)-(-)-camphanic acid (1R,2R)-2-tert-butoxycarbonyl-2-fluoro-cyclopentyl ester (7) and X-ray analysis. A model for enantioselection is proposed on the basis of the known structures of the dicationic complex [Ru(4a)(PNNP)] 2+ (2a; 4a is 2-tert-butoxycarbonylcyclopentanone), which is formed under catalysis conditions, and of its monocationic enolato analogue (3a). The stoichiometric reactions of 2a and 3a with NFSI in pure CH 2 Cl 2 and in the presence of substrate, product, or Et 2 O show that proton-transfer processes promoted by oxygen donors are pivotal in catalysis. Scheme 1Scheme 2

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. Reactions of sparteine-complexed lithiated carbamates with (Z)-alkenyl pinacol boronic esters and (E)-alkenyl neopentyl boronic esters gave (E)-syn- and (E)-anti-homoallylic alcohols, respectively, in greater than 96:4 er and 98:2 dr. In these reactions, a Lewis acid (MgBr(2) or BF(3) x OEt(2)) was required to promote both the 1,2-metalate rearrangement and the addition of the intermediate allylic boronic ester to the aldehyde. This methodology provides a general route to each of the three classes of homoallylic alcohols with high selectivity.

The chiral complexes [Ru(2)(PNNP)]2+ (4a) and [Ru(3)(PNNP)]2+ (4b), containing the non-enolized 1,3-dicarbonyl compounds 2-((tert-butoxy)carbonyl)cyclopentanone (2) or α-acetyl-N-benzyl-δ-valerolactam (3), were deprotonated to the enolato complexes 5a,b. Complex 4a has a pseudo-aqueous pK a value of 4.6 ± 0.5 (with pK a(Ph3PH+) = 2.7 as reference) and catalyzes the 1,4-addition of 2 to methyl vinyl ketone with up to 79% ee.

The chiral dicationic complexes [Ru(4a)(PNNP)]2+ (2a) and [Ru(4h)(PNNP)]2+ (2h, PNNP is (1S,2S)-N,N′-bis[o-(diphenylphosphino)benzylidene]cyclohexane-1,2-diamine), containing non-enolized 2-tert-butoxycarbonylcyclopentanone (4a) or α-acetyl-N-benzyl-δ-valerolactam (4h), were prepared from [RuCl2(PNNP)] (1) by double chloride abstraction with (Et3O)PF6, followed by reaction with the 1,3-dicarbonyl compound. The estimated aqueous pK a values for 2a (3.3 ± 0.3) and 2h (4.7 ± 0.1) were determined by deprotonation with Ph2NH and pyridine, respectively. The corresponding monocationic enolato complexes 3a and 3h were isolated and structurally characterized. Complex 2a catalyzes the 1,4-addition of 4a to methyl vinyl ketone with up to 93% ee when a CH2Cl2/Et2O (1:1) solvent mixture is used. Oxygen-containing cosolvents enhance both the rate and enantioselectivity of the Michael addition with a number of substrates. This observation is discussed in the context of our previous observation that the combined addition of diethyl ether and of β-keto ester 4a favors and accelerates the deprotonation of 2a in dichloromethane.

Abstract:The asymmetric hydroxylation and fluorination catalyst [Ru(OEt 2 ) 2 (PNNP)] 2+ (PNNP = chiral tetradentate ligand with a P 2 N 2 donor set) reacts with 1,3-dicarbonyl compounds to give dicationic adducts and, upon deprotonation, the corresponding enolato complexes. The relevance of these species to catalytic O-and F-transfer is investigated.