228418-82-4Relevant articles and documents
Regio- and stereoselective SN2′ reaction of an allylic picolinate in the synthesis of LY426965
Kobayashi, Yuichi,Yamaguchi, Kai,Morita, Masao
, p. 1826 - 1831 (2018/03/07)
Allylic substitution of secondary γ,γ-disubstituted allylic picolinates with ArMgBr-based copper reagents was applied to the synthesis of LY426965. Reduction of (R)-6-(PMB-oxy)-3-hexyn-2-ol of 93% ee (PMB = p-MeOC6H4CH2) using Red-Al gave (R,Z)-4-iodo-5-(PMB-oxy)hex-3-en-2-ol, which was later converted to the Me-substituted allylic picolinate by Pd-catalyzed coupling with MeZnI followed by esterification with picolinic acid. Allylic substitution with PhMgBr/Cu(acac)2 proceeded with high anti SN2′ selectivity (99%). Ozonolysis, addition of c-Hex-MgBr to the resulting aldehyde, and reductive amination with the piperazine derivative afforded LY426965.
Stereospecific Rhodium-Catalyzed Allylic Substitution with Alkenyl Cyanohydrin Pronucleophiles: Construction of Acyclic Quaternary Substituted α,β-Unsaturated Ketones
Turnbull, Ben W. H.,Oliver, Samuel,Evans, P. Andrew
supporting information, p. 15374 - 15377 (2015/12/26)
A highly regio- and stereospecific rhodium-catalyzed allylic alkylation of tertiary allylic carbonates with alkenyl cyanohydrin pronucleophiles is described. This protocol offers a fundamentally novel approach toward the synthesis of acyclic quaternary-substituted α,β-unsaturated ketones and thereby provides a new cross-coupling strategy for target directed synthesis. A particularly attractive feature with this process is the ability to directly couple di-, tri- and tetrasubstituted alkenyl cyanohydrin pronucleophiles to prepare the corresponding α,β-unsaturated ketone derivatives in a highly selective manner. Additionally, the chemoselective 1,4-reduction of the enone products provides rapid access to acyclic enantiomerically enriched α,α′-dialkyl-substituted ketones, which are challenging motifs to prepare using conventional enolate alkylation.
Chiral phosphoramide-catalyzed enantioselective addition of allylic trichlorosilanes to aldehydes. Preparative studies with bidentate phosphorus-based amides
Denmark, Scott E.,Fu, Jiping,Lawler, Michael J.
, p. 1523 - 1536 (2007/10/03)
On the basis of the mechanistic insight that more than one Lewis basic moiety (phosphoramide) is involved in the rate- and stereochemistry-determining step of enantioselective allylation, bidentate chiral phosphoramides were developed. Different chiral phosphoramide moieties were connected by tethers of methylene chains of varying length. The rate and enantioselectivity of allylation with allyltrichlorosilane promoted by the bidentate phosphoramides was found to be highly dependent on the tether length. A new phosphoramide based on a 2,2′-bispyrrolidine skeleton has been designed and afforded good yield, efficient turnover, and high enantioselectivity in allylation reactions. The synthesis of enantiopure 2,2′-bispyrrolidine was easily accomplished on large scale by photodimerization of pyrrolidine followed by resolution with L(or D)-tartaric acid. The scope of the allylation reaction was examined with variously substituted allylic trichlorosilanes and unsaturated aldehydes. This method has been applied to the construction of stereogenic, quaternary centers by the addition of unsymmetrically γ-disubstituted allylic trichlorosilanes.
Arylpiperazines having activity at the serotonin 1A receptor
-
, (2008/06/13)
A series of aryl piperazine compounds are effective pharmaceuticals for the treatment of conditions related to or affected by the serotonin 1A receptor; the compounds are particularly effective antagonists at that receptor, and are particularly useful for alleviating the symptoms of nicotine and tobacco withdrawal.
Enantioselective process for preparing arylated lactones and derivatives
-
Page 7-8, (2008/06/13)
This invention provides a process for the arylation of lactones to form to chiral and achiral aryllactones having high enantioselectivity where applicable.
Asymmetric Construction of Quaternary Centers by Enantioselective Allylation: Application to the Synthesis of the Serotonin Antagonist LY426965
Denmark, Scott E.,Fu, Jiping
, p. 1951 - 1953 (2007/10/03)
(Matrix Presented) Catalytic enantioselective allylation with a chiral bisphosphoramide was applied to the synthesis of LY426965, a serotonin antagonist. The key step, addition of a 3,3-disubstituted allyltrichlorosilane to benzaldehyde, provided the addu
Arylpiperazines having activity at the serotonin 1A receptor
-
, (2008/06/13)
A series of aryl piperazine compounds of the formula: or the pharmaceutically acceptable salts thereof, are effective pharmaceuticals for the treatment of conditions related to or affected by the serotonin 1Areceptor; the compounds are particularly effective antagonists at that receptor, and are particularly useful for alleviating the symptoms of nicotine and tobacco withdrawal.
