Asymmetric aza-[2,3]-Wittig sigmatropic rearrangements: chiral auxiliary control and formal asymmetric synthesis of (2S, 3R, 4R)-4-hydroxy-3-methylproline and (–)-kainic acid

Anderson, James C.; O'Loughlin, Julian M. A.; Tornos, James A.

doi:10.1039/b506198a

Cited by 31 publications

(6 citation statements)

References 51 publications

(24 reference statements)

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“…However so far the results reported are ambiguous. 54 The use of chiral bases (i.e. alkyllithium-sparteine complexes) has also been studied by Anderson, so far without success (due to the rate of epimerisation of the chiral lithiated intermediate being faster than that of the [2,3]-rearrangement).…”

Section: [23]-sigmatropic Aza-wittig Rearrangementmentioning

confidence: 99%

Quaternary centres bearing nitrogen (α-tertiary amines) as products of molecular rearrangements

et al. 2011

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Quaternary centres bearing a nitrogen substituent (α-tertiary amines and their derivatives) are found in a variety of bioactive molecules but pose a major challenge in synthesis, particularly when enantiomeric purity is required. Approaches comparable to those used for tertiary alcohols are typically hampered by the poor electrophilicity of imines, requiring powerful nucleophiles that may also act as bases. A set of powerful alternative approaches make use of the rearrangement of readily available precursors, often (but not always) with formation of a new tertiary carbon to nitrogen bond. In this Feature Article we review the scope, limitations and specificities of some of these rearrangements in order to illuminate their synthetic potential.

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Section: [23]-sigmatropic Aza-wittig Rearrangementmentioning

confidence: 99%

Quaternary centres bearing nitrogen (α-tertiary amines) as products of molecular rearrangements

et al. 2011

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“…This sequence has then been applied to the formal syntheses of 4-hydroxy-3-methyl proline and kainic acid (Scheme 4). 8…”

Section: Sigmatropic Rearrangementsmentioning

confidence: 99%

Stereocontrolled routes to β,β′-disubstituted α-amino acids

2009

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Owing to their significant abundance in natural products, chiral beta,beta'-disubstituted alpha-amino acids remain an important synthetic objective. Emphasis has been focused in this critical review on the great diversity of enantio- and diastereoselective methodologies to reach these highly functionalized compounds. The oldest and cutting edge synthetic methods are described in parallel with the synthesis of many relevant biologically active targets (224 references).

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“…The stereoselection from the rearrangements of (S)-6a,b (eqns. (3,4)) can be rationalised by analysing the proposed transition states for this pericyclic reaction (Fig. 1).…”

Section: Scheme 1 Retrosynthesismentioning

confidence: 99%

“…2 More recently we have summarised some of our attempted strategies towards preparing enantiomerically pure aza-[2,3]-rearrangement products and detailed the use of (−)-8 phenylmenthol as a chiral auxiliary. 3 An (−)-8-phenylmenthol ester of a glycine derived migrating group controlled the absolute stereochemistry of aza-[2,3]-Wittig sigmatropic rearrangements with diastereoselectivities of ∼3 : 1 with respect to the auxiliary and ca. 50% isolated yields of enantiomerically pure products.…”

Section: Introductionmentioning

confidence: 99%

Chirality transfer in the aza-[2,3]-Wittig sigmatropic rearrangement

2005

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The aza-[2,3]-Wittig sigmatropic rearrangements of substrates derived from enantiomerically pure alanine, valine and serine with phenyl and ester anion stabilising groups were investigated for their efficiency in chirality transfer. It was found that a methyl substituent at the stereogenic centre of the rearrangement precursors was inadequate to control the alkene stereoselectivity and enantioselectivity of the rearrangement. Ester stabilised anions of valine and serine derivatives were the most successful with up to 66% yield, 14 : 1 alkene (E)-stereoselection and 88% chirality transfer. A limitation to the steric bulk of the stereogenic centre was noted in that the substituent has to be bulky enough to dictate alkene stereoselection, but not too large to compromise the directing effect of the activating phenyldimethyl silyl substituent on the anion stabilising group. Experimental evidence suggested a possible complimentary coordinating effect of an O-MOM serine substituent, which may assist alkene stereoselectivity and enantioselectivity.

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Asymmetric aza-[2,3]-Wittig sigmatropic rearrangements: chiral auxiliary control and formal asymmetric synthesis of (2S, 3R, 4R)-4-hydroxy-3-methylproline and (–)-kainic acid

Cited by 31 publications

References 51 publications

Quaternary centres bearing nitrogen (α-tertiary amines) as products of molecular rearrangements

Quaternary centres bearing nitrogen (α-tertiary amines) as products of molecular rearrangements

Stereocontrolled routes to β,β′-disubstituted α-amino acids

Chirality transfer in the aza-[2,3]-Wittig sigmatropic rearrangement

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