Quaternary carbon centers Claisen rearrangement

Silylene transfer to a -unsaturated esters produces oxasilacyclopentenes and provides a new method for regio- and stereo-selective formation of enolate that can undergo facile and selective Ireland-Claisen rearrangements and aldol addition reactions to provide products with multiple contiguous stereocenters and quaternary carbon centers (Scheme 37). 

The synthesis of (-) and ( )-mesembranol (413) has been described in two reports construction of the quaternary carbon center in the former involved Claisen rearrangement (79S) (Scheme 48), whereas that in the latter case was performed by radical-mediated cyclization (74S) (Scheme 49). 

The next and particularly crucial phase of the synthesis was the construction of the quaternary carbon center associated with galanthamine as well as the formation of the furan or B-ring. While it took some time to establish the right sequence of reactions to realize such an outcome, this was eventually achieved in just three steps (Scheme 4). The first was the engagement of the allylic alcohol moiety within compound 15 in an Eschenmoser-Claisen (EC) rearrangement by treating it with the dimethyl acetal of... 

The Claisen rearrangement has also been routinely exercised for the stereocontrolled construction of quaternary carbon centers. For example, the conjugate addition of methyl cuprate to vinylogous ester 59 followed by in situ trapping of the enolate with allyl iodide gave the allyl vinyl ether 60, which was utilized for Claisen rearrangement to furnish 61 as a single diastereomer. ... 

As in the case of all variations of the Clasien rearrangement, the [3,3]-sigmatropic process is routinely applied for the construction of stereogenicity at quaternary carbon centers. During studies toward the total synthesis of meloscine, orthoester Johnson-Claisen rearrangement was utilized as the key bond formation event when many other attempts to construct the C5 quaternary stereocenter in this sterically-demanding environment failed. Treatment of 351 with trimethyl orthoacetate at elevated temperature readily afforded the ester 352 with moderate diastereoselection." ... 

Sigmatropic Rearrangement Zhou and coworkers applied an aza-[3,3]-Claisen rearrangement as the key step in their synthetic approach to isoschizogamine (55) (Scheme 4.12) [21]. Treatment of 52 with LiHMDS afforded the rearranged product 54 via the amide enolate 53. The enolate 53 adopted a boat-like transition state, allowing effective chirality transfer from aziridine to the newly formed quaternary carbon center. 

A chiral quaternary carbon center via an addition-rearrangement reaction of 3,3-disubstituted allyl morpholine (61) and benzyloxyacetyl chloride (56) was successfully constructed with 300 mol% of chiral Mgl2 (60) complex, and the corresponding Claisen adduct (62) was obtained in 97% ee and 94 6 syn anti selectivity (Scheme 4.18). 

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. 

Several factors contribute to the versatility of the ester enolate Claisen rearrangement. Among these are the ability to use a stoichiometric combination of the alcohol and the acid components, the relatively low temperature - of the pericyclic process that allows for the assembly of complex, highly functionalized structures, and the transformation of a carbon-oxygen into a carbon-carbon bond that lends itself easily to the assembly of contiguous quaternary centers. - ... 

The Kobayashi group has observed the intramolecular diastereoselective spirocyclization of racemic 2-haloindoles bearing a C3-tethered allylic alcohol [71, 72]. For example, CuCl-catalyzed intramolecular Ullmann coupling of 117 followed by spontaneous Claisen rearrangement of the intermediate pyranoindole 118 afforded, in a one-pot synthesis, the all-carbon quaternary center of spiro-oxindole 119 in 95% de (Scheme 31). The methodology has been extended to the synthesis of hexahydropyrroloindoles, e.g., ( )-debromoflustramine B and E. 

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