Toward a Versatile Allylation Reagent:  Practical, Enantioselective Allylation of Acylhydrazones Using Strained Silacycles

Abstract

A highly practical method for the enantioselective allylation of acylhydrazones has been developed. The previously reported strained silacycle reagent 1 reacts with a wide variety of acylhydrazones to give the hydrazide products with good enantioselectivity (83-89% ee, typically). It has been demonstrated that the products may be isolated without chromatography by recrystallization in >/=98% ee.

Diastereoselective Allylation of Carbonyl Compounds and Imines: Application to the Synthesis of Natural Products

“…Optimal results were obtained working in CH 2 Cl 2 at 10°C (method A, Table 48, entries 1−6). 115 The substrate scope was then studied under the optimized reaction conditions, and in general, yields and enantioselectivities were high for aromatic, heteroaromatic, and aliphatic aldehyde derived hydrazones. The only exception was the 3-pyridyl acetylhydrazone, which was allylated in only 23% ee (Table 48, entry 5).…”

Origins of Stereoselectivity in Strain‐Release Allylations

“…The model based on these transition states suggests the components important for the stereoselectivity of diazasilane reagents: 1) attack of aldehyde oxygen on an apical position of the Si center (anti to an N); 2) an antiperiplanar arrangement of an O lone-pair and the SiÀCl bond in the chair transition state; 3) location of the chlorine with the lone pair anti to the lone-pair of apical N. Studies of acylhydrazone allylations by Leightons oxazasilane reagents are in progress. [12] Figure 2. Transition-state geometries from HF/6-31G* optimizations and relative energies [kcal mol À1 ] from MP2/6-311 + + G** single-point energy calculations for the reaction of (R,R)-2 with acetaldehyde.…”

Chiral N‐Acylhydrazones: Versatile Imino Acceptors for Asymmetric Amine Synthesis

“…[54] With N-acylhydrazones, some early examples of allyl additions were achieved by Kobayashi et al using allylstannanes [55] [Equation (6)] and allylsilanes [56] [Equation (7)]. More recently, Leighton has explored chiral strain-activated allylsilane reagents [57] [Equation (8)], and Kobayashi has reported nucleophilic catalysis of allyltrichlorosilane addition [Equation (7)] using chiral sulfoxides; [58] both afford highly enantioselective addition to N-acylhydrazones. (6) (7) (8) In the additions of allylchlorosilanes to N-acylhydrazones, coordination of the N-acyl oxygen atom to the silicon may play an important role, as illustrated in two similar transition states proposed by Kobayashi and Leighton (Figure 6).…”