Asymmetric bromolactonization

Herein we will show a new and simple synthetic method for (S)-4 using asymmetric bromolactonization which has been the most dependable method for the chiral a-a-disubstituted a-hydroxy acids (ref. 3). 

Asymmetric bromolactonization (8, 421-423). Full details for synthesis of a,a-disubstituted a-hydroxy acids from a,/S-unsaturated acids by bromolactonization have been published.1... 

A modification of this asymmetric bromolactonization affords optically active a,/J-epoxy aldehydes (equation I).2 Thus treatment of the bromolactone 1 with... 

Asymmetric bromolactonization (8, 421-423) ct,fi-epoxy aldehydes(2R.3S)-Epoxy aldehydes (2) can be prepared in high optical yield by an extension of the asymmetric bromolactonization of N-(a,/(-unsaturated) acylprolines (1), as shown in the example. 

Variations on this cyclization methodology include the use of bromine, rather than iodine again, both lactones and ethers can be prepared.1,47,54-57 An asymmetric bromolactonization procedure affords a-hydroxy acids with good asymmetric induction.57-62... 

Asymmetric bromolactonization (8, 421-423). Detailed papers concerning this reaction have been published. For this reaction L-proline is definitely superior to open-chain L-amino acid derivatives where free rotation of the bond between the asymmetric center and the N atom is possible. 

Asymmetric Halolactonization. An asymmetric halolac-tonization reaction using proline as a chiral auxiliary has been reported. Optically active a-hydroxy acids (16) are prepared from a,p-unsaturated acids via the corresponding (S)-proline amide (13) involving an asymmetric bromolactonization step (eq 6) ... 

The unsaturated carboxylic acid (13) undergoes an asymmetric bromolactonization when treated with N-Bromosuccinimide in DMF. The bromolactone (14) and its diastereomer are obtained in a 94.5 5.5 ratio. Reduction and hydrolysis yields the a-hydroxy acid (16) in an overall optical yield of 90%. The same procedure gives chiral a-hydroxy ketones. ... 

A modification of the asymmetric bromolactonization leads to optically active a,p-epoxy aldehydes (18). Treatment of the bromolactone (14) with Sodium Methoxide results in the formation of the epimeric epoxy ester (17) in a ratio of 2 1 (eq 7). 

Asymmetric bromolactonization of 2-(2,3-dimethylacryloyl)-l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid gave derivatives of the 6,7-benzologue of (3) <77CL1109,79T2345). 

Cyclization of 3-(2-oxo-3,l-benzoxazin-l-yl)propionic acid in PPA at 1(X)-120°C gave 6,7-dihydro-l//,3//-5//-pyrido[3,l-j ][3,l]benzoxazine-3,7-dione (87EUP239129 90CPB1575). Asymmetric bromolactonization of 2-(2,3-dimethylacryloyl)-l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid in DMF in the presence of NBS afforded a diastereomeric mix-... 

Asymmetric bromolactonization of the acylproline (76) gives the lactone (77) in good yield and high stereoselectivity (99%). A review article on... 

Zhou L, Tan CK, Jiang X, Chen F, Yeung Y-Y. Asymmetric bromolactonization using amino-thiocarbamate catalyst. J. Am. Chem. Soc. 2010 132(44) 15474-15476. 

Murai K, Matsushita T, Nakamura A, Fukushima S, Shimura M, Fujioka H. Asymmetric bromolactonization catalyzed by a Cs-symmetric chiral trisimidazoline. Angew. Chem. Int. Ed. 2010 49(48) 9174-9177. 

Tan CK, Zhou L, Yeung Y-Y. Aminothiocarbamate-catalyzed asymmetric bromolactonization of 1,2-disubstituted olefinic acids. Org. Lett. 2011 13(10) 2738-2741. 

Whitehead DC, Fhaner M, Borhan B. A peptide hromoiodi-nane approach for asymmetric bromolactonization. Tetrahedron Lett. 2011 52(18) 2288-2291. 

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