1,2- vs. 1,4-addition of nucleophilic organometallics to nonracemic 2-(1-naphthyl)- and 2-cinnamyl-1,3-oxazolidines

Pridgen, Lendon N.; Mokhallalati, M. K.; Wu, Ming Jung

doi:10.1021/jo00030a035

Cited by 91 publications

(25 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…9 However, in the case of α,β-unsaturated imine substrates, the possibility of 1,2 v's 1,4-addition arises. Other research groups have addressed this question, and the following generalizations have been made for α,β-unsaturated imine substrates containing a βaminoalcohol auxiliary: 10 • organolithium, cerium and cuprate reagents undergo 1,2-addition; • Grignard reagents add exclusively in a 1,4-fashion.…”

Section: Methodsmentioning

confidence: 99%

High Asymmetric Induction in Anionic Amino-Cope Rearrangements Controlled by β-Aminoalcohol Auxiliaries

Allin¹,

Button²,

Baird³

1998

Synlett

View full text Add to dashboard Cite

Novel 3-amino-1,5-dienes were prepared with high diastereoselectivity by unprecedented 1,2-addition of allyl Grignard to α,β-unsaturated imines containing β-aminoalcohol auxiliaries.Asymmetric anionic amino-Cope rearrangement of the diastereoisomerically pure 3-amino-1,5-diene substrates proceeded to yield the target 3-substituted aldehyde in good yield and with high levels of asymmetric induction (up to 94% e.e.).There is growing interest in asymmetric variants of sigmatropic rearrangements. 1 We have recently initiated a programme aimed at developing the amino-Cope rearrangement as a novel synthetic cascade. Scheme 1 summarizes our ultimate goal, the one-pot synthesis of acyclic products containing (up to) three contiguous asymmetric centres via sigmatropic rearrangement (Step 1) and subsequent enamine derivatization (Step 2). Scheme 1Our group is the first to have demonstrated key steps of this protocol, including a successful tandem amino-Cope rearrangement/enamine derivatization reaction. 2 More recently we have established that an anionic variant of the amino-Cope rearrangement is possible, and that asymmetric induction can be achieved at a chiral centre created during the rearrangement of a diastereoisomerically pure substrate. 3 We believe that the asymmetric amino-Cope rearrangement has significant advantages over the analogous oxy-Cope rearrangement in terms of asymmetric induction. The reported axial/equatorial preference for an oxy-anion substituent in the proposed chair-like transition state of the oxy-Cope rearrangement can be low, leading to a product with a correspondingly low enantioselectivity. 4 For example, the asymmetric oxy-Cope and amino-Cope rearrangements can yield the same aldehyde product, but whereas the amino-Cope rearrangement has yielded the product with 75% e.e., 3 the oxy-Cope is known to lead to only 30% e.e. 4Our initial study into the asymmetric amino-Cope rearrangement suffered from drawbacks including low diastereoselectivity (1.3 : 1) in the preparation of the required 3-amino-1,5-diene substrates, and a maximum e.e. of only 75% in the amino-Cope rearrangement. 3 The diastereoselectivity obtained during preparation of the 3-amino-1,5-diene substrates is of key importance to our work, since each diastereoisomer is known to lead to opposite enantiomers of the rearrangement product, 3 hence separation of the substrate diastereoisomers is an additional problem if one aims to achieve high enantioselectivity in the sigmatropic rearrangement. The results outlined in this current paper describe the synthesis of the required 3-amino-1,5-diene substrates with much improved levels of diastereoselectivity using β-aminoalcohol chiral auxiliaries, and a significant increase in product e.e. during the amino-Cope rearrangement of these novel substrates.Following our preliminary work, we reasoned that an increase in the steric bulk of the amine component would result in a corresponding increase in product enantioselectivity during the amino-Cope rearrangement. This postulate was based on our...

show abstract

Section: Methodsmentioning

confidence: 99%

High Asymmetric Induction in Anionic Amino-Cope Rearrangements Controlled by β-Aminoalcohol Auxiliaries

Allin¹,

Button²,

Baird³

1998

Synlett

View full text Add to dashboard Cite

show abstract

“…N-Unsubstituted 1,3-oxazolidines have been previously reported but without spectroscopical data or an assignment of stereochemistry. 10,11 However, it has been reported that the related N-tosyl-1,3-oxazolidine series form the syn diastereomer preferentially. 7 Having experienced difficulties with the stability of the products and the assignment of stereochemistry for 4a-e we then turned our attention to the reaction between ( 2 (3) are known to form stable aminals, which are frequently used in asymmetric synthesis.…”

Section: Green Contextmentioning

confidence: 99%

“…This reaction seemed to be particularly suited to the purpose of our investigation as the two potential diastereomers are in thermal equilibrium with one another via an iminium ion intermediate, 7,8 thus allowing the equilibration of the diastereomeric oxazolidines in the absence of any other reagent. Furthermore, homochiral 1,3-oxazolidines have been used as valuable chiral auxiliaries in a number of asymmetric transformations [9][10][11][12][13] and have been employed to effect separation of enantiomers of a-chiral aldehydes. 14,15…”

Section: Introductionmentioning

confidence: 99%

Highly diastereoselective synthesis of 1,3-oxazolidines under thermodynamic control using focused microwave irradiation under solvent-free conditions

Kuhnert

Danks

2001

Green Chem.

View full text Add to dashboard Cite

A number of 1,3-oxazolidines, derived from enantiomerically pure amino alcohols such as (2)-ephedrine and (+)-pseudoephedrine, have been synthesised under solvent-free conditions using a focused microwave reactor. The condensation reaction between the amino alcohol and an aldehyde yields 1,3-oxazolidines in excellent yields and diastereoselectivities. Prolonged microwave irradiation increases the diastereoselectivity of the reaction and produces the thermodynamically more stable diastereomer. JHC This journal is

show abstract

“…In this context, the enantioselective reduction of prochiral ketimines is among the most reliable and efficient approaches to obtain the corresponding optically active amines [2][3][4], which are themselves found in various natural or medicinal compounds [5][6][7][8]. Likewise, several methodologies have been developed for the enantioselective reduction of imines [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28], the asymmetric hydrogenation of functionalized imines such as acyclic aromatic N-aryl imines [29], ␣-fluorinated iminoesters [30,31] and acyclic imines [32], with a variety of complexes of Ir [32,33], Ru [34], Rh [19] and organocatalysts [35,36] have been employed in asymmetric hydrogenations and/or transfer hydrogenations of imines. Noteworthy, Co 2 (CO) 8 /modified phosphine complexes have never been used as catalysts in asymmetric hydrogenation of imines, even though, phosphine dicobalt octacarbonyl derivatives play an important role as catalytic promotors in other organic transformations, for example: hydroformylation of alkenes (also known as oxo process discovered in 1938 by Otto Roelen) [37,38], amidocarbonylation reaction …”

Section: Introductionmentioning

confidence: 99%

The first example of asymmetric hydrogenation of imines with Co2(CO)8/(R)-BINAP as catalytic precursor

Amézquita‐Valencia¹,

Cabrera²

2013

Journal of Molecular Catalysis A: Chemical

View full text Add to dashboard Cite

1,2- vs. 1,4-addition of nucleophilic organometallics to nonracemic 2-(1-naphthyl)- and 2-cinnamyl-1,3-oxazolidines

Cited by 91 publications

References 2 publications

High Asymmetric Induction in Anionic Amino-Cope Rearrangements Controlled by β-Aminoalcohol Auxiliaries

High Asymmetric Induction in Anionic Amino-Cope Rearrangements Controlled by β-Aminoalcohol Auxiliaries

Highly diastereoselective synthesis of 1,3-oxazolidines under thermodynamic control using focused microwave irradiation under solvent-free conditions

The first example of asymmetric hydrogenation of imines with Co2(CO)8/(R)-BINAP as catalytic precursor

Contact Info

Product

Resources

About