1.Cross-metathesis reactions as an efficient tool in the synthesis of fluorinated cyclic beta-amino acids.
Fustero S1, Sánchez-Roselló M, Aceña JL, Fernández B, Asensio A, Sanz-Cervera JF, del Pozo C. J Org Chem. 2009 May 1;74(9):3414-23. doi: 10.1021/jo900296d.
The synthesis of enantiomerically pure, cyclic, gamma,gamma-difluorinated beta-amino acids with various ring sizes has been carried out with a cross-metathesis (CM) reaction being one of the key steps, followed by a Dieckmann-type condensation to bring about the cyclization. Subsequent catalytic hydrogenation under microwave irradiation with (-)-8-phenylmenthol as a chiral auxiliary led to the successful chemo- and diastereoselective chemical reduction of the resulting cyclic beta-enamino esters. The efficiency and scope of the CM reaction with different types of fluorinated imidoyl chlorides and unsaturated esters has also been studied in order to determine the optimal reaction conditions with regard to selectivity and reactivity.
2.Dimethylzinc-mediated addition of alkenylzirconocenes to alpha-keto and alpha-imino esters.
Wipf P1, Stephenson CR. Org Lett. 2003 Jul 10;5(14):2449-52.
[reaction: see text] Hydrozirconation of alkynes followed by in situ transmetalation to dimethylzinc and 1,2-addition to activated ketones and N-diphenylphosphinoylimines leads to tertiary allylic alcohols and amines in high overall yield. With 8-phenylmenthol as the chiral auxiliary, si-face attack proceeds in good to excellent diastereoselectivities.
3.Asymmetric synthesis of fluorinated cyclic beta-amino acid derivatives through cross metathesis.
Fustero S1, Sanchez-Roselló M, Sanz-Cervera JF, Aceña JL, Del Pozo C, Fernandez B, Bartolomé A, Asensio A, Ramírez de Arellano C. Org Lett. 2006 Sep 28;8(20):4633-6.
The asymmetric synthesis of several fluorinated cis-2-aminocycloalkane carboxylic acids (cis-2-ACACs) with a cross metathesis (CM) reaction as the key step has been carried out, constituting the first time a metathesis protocol has been undertaken with fluorinated imidoyl chlorides. Subsequent chemoselective hydrogenation of the olefin moiety, Dieckmann condensation, and stereoselective reduction of the iminic double bond afforded the corresponding beta-amino esters with several ring sizes. The asymmetric version of the process was achieved by using (-)-8-phenylmenthol as a chiral auxiliary.
4.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 JC1, O'Loughlin JM, Tornos JA. Org Biomol Chem. 2005 Aug 7;3(15):2741-9. Epub 2005 Jun 30.
A survey of 16 different chiral auxiliaries and a variety of strategies found that an (-)-8-phenylmenthol ester of a glycine derived migrating group can control the absolute stereochemistry of aza-[2,3]-Wittig sigmatropic rearrangements with diastereoselectivities of ca. 3 : 1 with respect to the auxiliary. In two specific examples, ca. 50% yields of enantiomerically pure products were obtained after chromatographic purification. These were synthetically manipulated with no erosion of stereochemistry into intermediates that completed formal asymmetric syntheses of (+)-HyMePro and (-)-kainic acid.