Chiral Phosphoramide-Catalyzed Enantioselective Addition of Allylic Trichlorosilanes to Aldehydes. Preparative and Mechanistic Studies with Monodentate Phosphorus-Based Amides

Abstract

The addition of allylic trichlorosilanes to benzaldehyde promoted by chiral phosphoramides to give the enantioenriched homoallylic alcohol has been investigated. In a survey of Lewis bases as activators for the addition of allyltrichlorosilane to benzaldehyde, phosphorus-based amides have been found to be the most effective promoters. To achieve asymmetric induction, chiral phosphoric triamides derived from chiral diamines have been developed and applied in the allylation reaction albeit with modest enantioselectivities. The addition of 2-butenylsilanes was highly diastereoselective, suggesting a closed, chair-like transition structure. A detailed mechanistic study has been carried out to probe into the origin of activation. From a combination of nonlinear effects and kinetics studies, the reaction was found to likely involve two phosphoramides in both the rate and stereochemistry determining steps. These studies provided the background for the development of highly selective and reactive catalysts.

Total synthesis of (+)-papulacandin D

“…Gratifyingly, allylation of 4 using chiral bisphosphoramide ( R,R )- 65 smoothly provided 70 in good yield and excellent diastereomeric selectivity (88%, dr 96:4). The expected C(7") S configuration30 was confirmed by analysis of the corresponding Mosher esters 33. Olefin metathesis with acrolein using Grubb's 2 nd generation catalyst, and protection of the C(7") hydroxyl group with TESCl gave 72 in 91% yield for the two steps.…”

“…Fortunately, an enantioselective allylation method developed in these laboratories, namely the chiral bisphosphoramide-catalyzed allylation reaction of allyltrichlorosilanes and aldehydes, was successful 30. Thus, the addition of allyltrichlorosilane (2.0 equiv) to 61 using 0.05 equiv of chiral bisphosphoramide ( R,R )- 65 at −78 °C for 8 h afforded the desired homoallylic alcohol ( S )- 62 in 76% yield with an enantiomeric ratio of 95:5 (Table 5, entry 5).…”

Lewis‐Base‐Katalyse in der organischen Synthese

“…Entsprechend ließen kinetische Studien mit 224 und 261 [319] einen prinzipiell ähnlichen Mechanismus erkennen wie bei Phosphoramid-katalysierten Reaktionen von Allyltrichlorsilan. [298] Die Reaktion von Benzaldehyd mit Cyclohexanontrichlorsilylether (259) ergab eine Abhängigkeit erster Ordnung von dem größeren Katalysator 261. Das lässt auf ein fünffach koordiniertes Siliconium-Kation im Übergangszu-stand LXVI der C-C-Verknüpfung schließen.…”

Pentafluorophenyl carbonyl compounds in the Reformatsky-type reactions promoted with Fe(CO)5-based metal complex systems

“…Chiral amino alcohols obtained from b-hydroxy nitriles are of great importance because of their biological activity and the possible applicability to asymmetric synthesis as ligands [28,29]. The addition of methyl bromoacetate, the typical Reformatsky reagent, to aldehyde 1 occurs at 110 8C to give 3-hydroxy-3-pentafluorophenylpropionic acid methyl ester (8) in good yield; it is accompanied by the formation of 3 as a by-product in the form of a mixture of meso-and D,L-forms.…”

“…are assigned to Zaitsev-Barbier-Reformatsky reactions [1][2][3][4][5]. Various metals are involved in these reactions such as zinc [4], magnesium [6] and more recently samarium [7], silicon [8], indium [5], etc. Although the common conditions for above reactions are continuously being improved, certain difficulties exist for carrying out them such as the need to use anhydrous and volatile solvents and inert atmosphere, low temperatures, heterogeneous medium, effective agitating and activating a metal surface.…”