98171-05-2

Upstream product

• 75-77-4 chloro-trimethyl-silane 
• 74059-55-5 (1S,2S)-N-methyl-ψ-ephedrine propionate 
• 1201-56-5 (1S,2S)-N-Methylpseudoephedrine 
• 53135-04-9 (1R,2S)-(2-Dimethylamino-1-phenyl)propyl propanoate 
• 552-79-4 (-)-N-methylephedrine 

Downstream Products

• 94199-26-5 (2S,3R)-methyl 3-hydroxy-2-methyl-3-phenylpropionate 
• 76549-03-6 methyl (2S,3S)-3-hydroxy-2-methyl-3-phenylpropanoate 
• 76549-05-8 methyl (2R,3R)-3-hydroxy-2-methyl-3-phenylpropanoate 
• 36041-80-2 (2R,3S)-methyl 3-hydroxy-2-methyl-3-phenylpropanoate 
• 108393-30-2 (2R,3R,4R)-5-(benzyloxy)-2,4-dimethyl-1,3-pentanediol 
• 108393-28-8 (2S,3R,4S)-5-benzyloxy-2,3-dimethylpentane-1,4-diol 
• 102210-04-8 (2R,3S,4R)-5-Benzyloxy-2,4-dimethyl-pentane-1,3-diol 
• 134833-53-7 (1'R,2'S)-(2'-Dimethylamino-1'-phenylpropyl) (4E)-3-hydroxy-2,4-dimethylhex-4-enoate 
• 138133-37-6 (1'R,2'S)-(2'-Dimethylamino-1'-phenylpropyl) (4E)-3-(tert-butyldimethylsiloxy)-2,4-dimethylhex-4-enoate 
• 98171-06-3 (2R,3S)-3-Hydroxy-2-methyl-3-phenyl-propionic acid (1R,2S)-2-dimethylamino-1-phenyl-propyl ester 
• 98171-06-3 (2S,3S)-3-Hydroxy-2-methyl-3-phenyl-propionic acid (1R,2S)-2-dimethylamino-1-phenyl-propyl ester 
• 98171-06-3 (2S,3R)-3-Hydroxy-2-methyl-3-phenyl-propionic acid (1R,2S)-2-dimethylamino-1-phenyl-propyl ester 
• 98171-06-3 (2R,3R)-3-Hydroxy-2-methyl-3-phenyl-propionic acid (1R,2S)-2-dimethylamino-1-phenyl-propyl ester 
• 98171-06-3 (2R,3S)-3-Hydroxy-2-methyl-3-phenyl-propionic acid (1S,2S)-2-dimethylamino-1-phenyl-propyl ester 

Relevant academic research and scientific papers

Total synthesis of piericidin A1 and B1 and key analogues

Full details of the total synthesis of piericidin A1 and B1 and its extension to the preparation of a series of key analogues are described including ent-piericidin A1 (ent-1), 4′-deshydroxypiericidin A1 (58), 5′-desmethylpiericidin A1 (73), 4′-deshydroxy-5′- desmethylpiericidin A1 (75), and the corresponding analogues 51, 59, 76, and 77 bearing a simplified farnesyl side chain. The evaluation of these key analogues, along with those derived from their further functionalizations, permitted a scan of the key structural features providing new insights into the role of the substituents found in both the pyridyl core as well as the side chain. A strategic late stage heterobenzylic Stille cross-coupling reaction of the pyridyl core with the fully elaborated side chain permitted ready access to the analogues in which each half of the molecule could be systematically and divergently modified. The pyridyl cores were assembled enlisting inverse electron demand Diels-Alder reactions of N-sulfonyl-1-azabutadienes, while key elements of side chain syntheses include an anti selective asymmetric aldol to install the C9 and C10 relative and absolute stereochemistry (for natural and ent-1) and a modified Julia olefination for formation of the C5-C6 trans double bond with convergent assemblage of the side chains.

TiCl4-Mediated Reactions of the Silyl Ketene Acetals Derived from N-Methylephedrine Esters: An Asymmetric Variant of the Mukaiyama Reaction

The TiCl4-mediated reaction between silyl ketene acetals 2 and benzaldehyde was chosen as a model for mechanistic studies.The influence of the silyl ketene acetal double-bond geometry, the C-1/C-2 relative configuration of N-methylephedrine, and different modes of addition and molar ratios of reagents on the stereochemical outcome of the reaction was investigated.On the basis of these results and of literature data, an octahedral, six-coordinate titanium complex was proposed as the transition-structure model.This model helps to rationalize some of the experimental data (e.g., the anti-syn ratios with aldehydes and imines).The TiCl4-mediated additions of the E silyl ketene acetal derived from (1R,2S)-N-methylephedrine propionate 1 (R=Me) to racemic 3-(benzyloxy)-2-methylpropionaldehyde (11) (kinetic resolution), (+)-(S)-11 (mismatched pair), and (-)-(R)-11 (matched pair) were studied.In the matched pair case three contiguous stereocenters were established with complete selectivity.The Mukaiyama-Michael additions of 1 (R = Me) to vinyl ketones were also studied.By this route α-methyl-δ-keto esters were obtained in 72-75 percent ee.

STEREOSELECTIVE ALDOL REACTIONS USING TiCl4 AS STEREOCHEMICAL TEMPLATE

TiCl4 mediated aldol condensations establish multiple contiguous chiral centers in an almost complete enantio- and diastereoselective way.