Palladium-Catalyzed Asymmetric Addition of Pronucleophiles to Allenes

Abstract

Simple additions are the most atom economic way to effect alkylations. The ability to effect the hydrocarbonation of allenes asymmetrically then becomes a highly efficient alkylation protocol. The first example of such a protocol involves the ability of a palladium(0) catalyst derived from palladium trifluoroacetate dimer and the bis-2-diphenylphosphinobenzamide of trans-1,2-diamininocyclohexane to catalyze additions to benzyloxyalkene. Various substituted Meldrum's acids including hydroxy Meldrum's acid react well in the presence of 1 mol % trifluoroacetic acid to give one regioisomer with ee's ranging from 82 to 99%. Switching to azlactones to access unusual quarternary amino acids requires somewhat more basic conditions. Thus, use of 2 mol % potassium alpha-butoxide and 20 mol % hippuric acid leads to a smooth reaction to produce a simple regiosomer. This nucleophile raises the question of facial selectivity with respect to both the nucleophile and the electrophile. Excellent diastereoselectivity (dr 13-20:1) and enantioselectivity (85-94% ee) are obtained. Thus, a new approach for asymmetric allylic alkylations of carbon pronucleophiles by simple additions provides a very efficient, more atom economic strategy for asymmetric C-C bond formation.

Enantioselective Palladium‐Catalyzed Addition of 1,3‐Dicarbonyl Compounds to an Allene Derivative

“…Representative procedure for addition of Meldrums acid derivatives 2 to allene 11 5-(1-Benzyloxy-allyl)-2,2,5-trimethyl- [1,3]-dioxa-4,6-dione (13 a): [13] In a 4 mL Minivert pressure vial, a mixture of [Pd(OTFA) 2 ] (6.7 mg), ligand (R,R)-12 (17 mg) and methyl Meldrums acid 2 a (316.3 mg, 2.0 mmol) was evacuated and flushed with Ar three times and then diluted with CH 2 Cl 2 (4.5 mL). Then, a freshly prepared 1 m solution of TFA in CH 2 Cl 2 (20 mL) was added by syringe.…”

“…After 30 min of stirring at RT, allene 11 (2.0 mmol) was added by syringe. After stirring overnight, the product was purified by direct flash chromatography on silica gel (3:2 petroleum ether/Et 2 O) to yield 13 a [13] (527.7 mg, 87 %) as a colorless oil, which solidified upon standing, with an ee of 97 %. Enantiomeric excess was determined by chiral HPLC (Chiralcel AD, heptane/2-propanol (99:1), flow: Representative procedure for addition of 1,3-diketones to allene 11 3-(1-Benzyloxy-allyl)-3-furan-2-ylmethyl-pentane-2,4-dione (16 e): Degassed CH 2 Cl 2 (0.7 mL) was added to a mixture of ligand (R,R)-12 (8.85 mg, 3.75 mol %), (allyl) 2 Pd 2 Cl 2 (1.87 mg, 1.5 mol %) and PhCO 2 H (2.09 mg, 5.0 mol %), and the resulting mixture was allowed to stir at RT for !…”

“…[12] More recently, a preliminary report of the first enantioselective version of this process from our laboratory appeared. [13] Through the use of two distinct conditions, both Meldrums acid derivatives [Eq. (2)] and azalactones were regioselectively added to benzyloxyallene providing branched products with high regio-and enantioselectivity.…”

Metal‐Catalyzed Enantioselective Allylation in Asymmetric Synthesis

“…13:1 to 20:1) and 85-94 % ee (Scheme 74). [231] The asymmetric ring expansion of allenylcyclobutanols 233 was realized by Trost and Xie by using a similar hydropalladation to generate the p-allylpalladium intermediate 236, which was followed by the ring expansion and asymmetric substitution with the in situ generated carbon nucleophile to afford 2-vinyl-2-alkoxycyclopentanone 234 (Scheme 75). [232] Scheme 71.…”

Metallkatalysierte enantioselektive Allylierungen in der asymmetrischen Synthese

“…13:1 bis 20:1) und 85-94 % ee erhalten (Schema 74). [231] Nach einen ähnlichen Mechanismus realisierten Trost et al die asymmetrische Ringerweiterung der Allenylcyclobutanole 233: Der Hydropalladierung zum intermediären pAllylpalladium-Komplex 236 folgen die Ringerweiterung und die asymmetrische Substitution mit dem in situ gebildeten Kohlenstoffnucleophil zu den 2-Vinyl-2-alkoxycyclopentanonen 234 (Schema 75).…”