Rearrangements, Claisen stereoselectivity

Marshall, J. A. Stereochemical control in the ester enolate Claisen rearrangement. Stereoselectivity in silyl ketene acetal formation. Chemtracts Org. Chem. 1991,4,154-157. 

Claisen rearrangement The Ireland-Claisen rearrangement Stereoselective Reduction of p-Hydroxy Ketones... 

The stereochemical outcome of the reaction is determined by the geometry of the transition state for the Claisen rearrangement a chairlike conformation is preferred,and it proceeds strictly by an intramolecular pathway. It is therefore possible to predict the stereochemical course of the reaction, and thus the configuration of the stereogenic centers to be generated. This potential can be used for the planning of stereoselective syntheses e.g the synthesis of natural products. 

Hydroxyalkyl)porphyrins,84-85 I07b 109 easily accessible from porphyrins by Friedel-Crafts acylation and subsequent reduction, undergo a stereoselective Claisen rearrangement with N,N-dimethylacetamide dimethyl acetal. The substitution pattern and the stereochemical arrangement of the derived chlorins match those of naturally occurring chlorins9 (see Section 1.2.1.2.). 

The high catalytic activity also enabled aza-Claisen rearrangements to form Al-substituted quaternary stereocenters (Fig. 26) [71]. The catalyst does not need to distinguish between differently sized substituents on the double bond of 49 (e.g., R = CDa, R = CHs, ee = 96%), indicating that coordination of the olefin is the stereoselectivity predetermining step. The imidate-N-atom subsequently attacks intermediate 47-1 from the face remote to the Pd-center totally resulting in a... 

The stereoselectivity of silyl ketene acetal Claisen rearrangements can also be controlled by specific intramolecular interactions.246 The enolates of a-alkoxy esters adopt the Z-configuration because of chelation by the alkoxy substituent. 

The synthesis in Scheme 13.44 is also based on a carbohydrate-derived starting material. It controlled the stereochemistry at C(2) by means of the stereoselectivity of the Ireland-Claisen rearrangement in Step A (see Section 6.4.2.3). The ester enolate was formed under conditions in which the T -enolate is expected to predominate. Heating the resulting silyl enol ether gave a 9 1 preference for the expected stereoisomer. The... 

As shown earlier in many examples, the Claisen rearrangement of allyl vinyl ethers also provides a very powerful method for carbon-carbon bond formation in domino processes. Usually, the necessary ethers are formed in a separate step. However, both steps can be combined in a novel domino reaction developed by Buchwald and Nordmann [306]. This starts from an allylic alcohol 6/4-102 and a vinyl iodide 6/4-103, using copper iodide in the presence of the ligand 6/4-104 at 120 °C to give 6/4-105 (Scheme 6/4.25). The reaction even allows the stereoselective formation of two adjacent quaternary stereogenic centers in high yield. 

An intramolecular nitrone 1,3-dipolar cycloaddition reaction to give 46 from 45 followed by reductive N-O bond cleavage afforded a stereoselective synthesis of the tetrahydro 177-1-benzazepines 47 the nitrone precursors 44 were prepared in turn by a Claisen rearrangement from an IV-allylamine <06SL2275>. 

Scheme 18.43 Stereoselective synthesis of enprostil by orthoester-Claisen rearrangement [125a] (THP = tetrahydropyranyl).

Further variations of the Claisen rearrangement protocol were also utilized for the synthesis of allenic amino acid derivatives. Whereas the Ireland-Claisen rearrangement led to unsatisfactory results [133b], a number of variously substituted a-allenic a-amino acids were prepared by Kazmaier [135] by chelate-controlled Claisen rearrangement of ester enolates (Scheme 18.47). For example, deprotonation of the propargylic ester 147 with 2 equiv. of lithium diisopropylamide and transmetallation with zinc chloride furnished the chelate complex 148, which underwent a highly syn-stereoselective rearrangement to the amino acid derivative 149. 

The Claisen rearrangement, discovered in 1912, has proven to be a powerful tool for the stereoselective generation of C—C bonds69. It is widely employed in complex multistep syntheses (see, for example, References 86-89) and has inspired many variations, including the Carroll (1940), Eschenmoser (1964), Johnson (1970), Ireland (1972) and Reformatsky-Claisen (1973) reactions69. 

Alkylidene cyclohexenes were synthesized stereoselectively from bis-allyl silylketene acetals derived from cyclohexenones93. As shown in equation 66, Ireland Claisen rearrangement of ester 133 gave only E-diene 136. Reaction of 133 with potassium... 

Only limited precedent exists for the stereoselective enolization and subsequent condensation of a-heteroatom-substituted esters 48a and 48b (eq. [29]). Ireland has examined the enolization process for a-amino ester derivatives where the Claisen rearrangement (chair-preferred transition states) was employed to ascertain enolate geometry (Scheme 10) (43). These results imply that 48a [X = N(CH2Ph)2 ] exhibits only modest selectivity for ( )-enoIate formation under the... 

In the particular case in which the carbonyl group belongs to a carboxylic acid derivative, such as an ester (17) or an amide (18) (or other functional groups which may be converted into it by a FGI), then they may be disconnected according to the "orthoacetate-modification" of the retro-Claisen rearrangement (Schemes 7.7 and 7.8) developed mainly by Eschenmoser [7] and Ziegler [8], independently, in the synthesis of alkaloids, and Johnson in a very simple and yet highly stereoselective synthesis of squalene [9]. 

A highly stereoselective Claisen rearrangement was used to synthesize AE, 1 OZ-tetradecadien-1 -yl acetate, principal component... 

The Claisen rearrangement of allyl vinyl ethers is a classic method for the stereoselective synthesis of y,J-unsaturated esters. The allylic C-H activation is an alternative way of generating the same products [135]. Reactions with silyl-substituted cyclohexenes 197 demonstrate how the diastereoselectivity in the formation of 198 improves (40% to 88% de) for the C-H insertion reactions as the size of the silyl group increases (TMS to TBDPS) (Tab. 14.14). Indeed, in cases where there is good size differentiation between the two substituents at a methylene site, high diastereo- and enantioselectivity is possible in the C-H activation. 

X.J. Wang, S.A. Hart, B. Xu, M.D. Mason, J.R. Goodell, F.A. Etzkorn, Serine-c/s-proline and Serine-frans-proline isosteres Stereoselective synthesis of (Z)- and ( )-alkene mimics by still-wittig and ireland-claisen rearrangements, J. Org. Chem. 

Langlois and co-workers ° developed a stereoselective hetero-Claisen rearrangement of camphor-based oxazoline A -oxides 300, available from hydroxylami-noisobomeol 298 and orthoesters 299. The rearrangement, initiated by acylation of... 

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