Ferrier II Reaction

This process (also known as the Ferrier II Reaction ) has proved to be of considerable value for the efficient, one-step conversion of 5,6-unsaturated hexopyranose derivatives into functionalized cyclohexanones useful for the preparation of such enantiomerically pure compounds as inositols and their amino, deoxy, unsaturated and selectively O-substituted derivatives, notably phosphate esters. In addition, the products of the carbocyclization have been incorporated into many complex compounds of interest in biological and medicinal chemistry. ... 

The Ferrier (II) reaction is quite efficient to form six membered carbocycles, but is unsuitable to prepare cyclopentitols. Five membered enollactone 14 was converted to the cyclopentanone derivative 16 as a single epimer upon treatment by LiAlH(OtBu)3 (Scheme 4) [41]. Spectroscopic studies established some mechanistic details. Accordingly, the hydride of the reducing agent rapidly added to the carbonyl and formed with the metal a stable alu-minate complex. The carbocydization occurred by protonation followed by fragmentation and aldol type cyclization process. 

The Ferrier II reaction, a carbocyciization reaction, is of widespread use as a tool for the conversion of glycosides into cyclitols [ 183,184,185]. Newer examples for the utilization of the reaction conducted under catalytic conditions [186,187] have appeared in the recent literature. Compound 221 is converted into cyclohexanone 222 on the way to (—)-mesembranol [188] (O Scheme 48). Compound 223 is transformed to the enone 224, the precursor of several new cyclitol derivatives [189,190,191]. 

This reaction was initiaiiy reported by Perrier in 1979. It is a mercury (II) salt -induced or promoted conversion of 5-enopyranosides into cyclohexanones with stereochemical control, by which substituents at positions 3 and 5 are predominantly in a trans relationship. To differentiate from another reaction also discovered by Perrier (called the Perrier Reaction), this reaction is known as the Ferrier-II rearrangement, " Ferrier-II carbocyclization, Perrier carbocyclization, or Ferrier-II reaction. Occasionally, it is also referred to as the Perrier Reaction. Therefore, it is called the Ferrier-II rearrangement in this book. It is useful in the conversion of carbohydrates into carbosugars, myo-inositols, and other natural products. ... 

The name Ferrier (I) reaction, is occasionally used to differentiate this transformation from another reaction, also described by Prof. Ferrier, in which hex-5-enopyranosyl derivatives are transformed into functionalized cyclohexanones, even though this process is also named Ferrier carbocycli-zation, or Ferrier (II) reaction (a) R. J. Ferrier,/. Chem. Soc., Perkin Trans. 1, 1979, 1455 (b) R. J. Ferrier and S. Middleton, Chem. Rev., 1993, 93, 2779. 

Sugar enol-ethers, which inherently carry both the masked nucleophilic and electrophilic functions, were converted to carbocycles in different reactions. Among the carbocyclization methods the Ferrier (II) cyclization of hex-5-enopyranosides affording six membered carbocycles in the presence of Hg(II) salts is perhaps the most popular one (Scheme 3) [32], This remarkable reaction has provided a practical route to a large variety of bioactive substances such as aminocyclitols [33], pseudosugars [34], inositols [35], and other complex hexitols [36]. 

The so-called Ferrier (II) rearrangement is the most common approach to carbasugars, although it requires use of mercury and a reaction time (several hours). Pohl et al. [59], found that the Ferrier (II) rearrangement of 78 into 79 in the presence of palladium dichloride can be performed in less time and with higher yields by use of microwave irradiation rather than conventional heating (Scheme 12.37). 

Subsequently, the same group demonstrated an asymmetric synthesis of 3-amino aldehydes via catalytic double-bond isomerization/enantioselective aza-Petasis-Ferrier rearrangement reaction (Scheme 2.93) [128]. Similarly, the hemiaminal allyl ether substrates 346 were first isomerized by Ni(II) complexes to stereoselectively form Z-configured vinyl ethers 347, which then underwent a phosphoric acid-catalyzed... 

Thioglycosides were the first example of an anomeric derivatization that serves the dual role of protection and activation. They were introduced in glycosylation reactions by Ferrier et al. in 1973, who used mercury(II) salts as activator.1 After the development of improved methods of their synthesis and activation, thioglycosides together with trichloroacetimidates are now the most commonly used glycosyl... 

R. J. Ferrier and S. R. Haines, Alkenes from 4-bromohexofuranose esters reactions of 5-deoxyald-4-enofuranose derivatives in the presence of mercury(II) ions, J. Chem. Soc. Perkin Trans. 1 1689 (1984). 

Ferrier, R. J. Unsaturated carbohydrates. II. Three reactions leading to unsaturated glycopyranosides. J. Chem. Soc., Abstracts 1964, 5443-5449. 

The same catalyst has been used by this research group in synthesis of j -amino-aldehydes (146) by combining two catalytic reactions, i.e. a Ni(II) complex-catalyzed isomerization of a double bond and a chiral phosphoric acid (127)-catalyzed aza-Petasis-Ferrier rearrangement in a highly dia-stereo- and enantioselective manner (Scheme 39). ... 

As part of a biochemical study on the bio ntheas of 2-deoxystreptamine, the preparations of 2-deoxy-5cy//o-inose and [2,2- H2]-2-deoxy-scy/to-inose have been described, the former by a multi-step synthesis from /nyo-inositol and the latter involving a modified Ferrier reaction." The Ferrier reaction has also been used to construct the carbocyclic framework of the carbocylic analogue of Lipid X 73. The stereochemistry of the Pd (II) cataly2ed Ferrier reaction has also been studied and concluded to give the same products to that observed in the Hg catalyzed reaction. The synthesis of L-sugar derivatives from L-quebrachitol is mentioned in Chapter 2 and 16. 

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