131865-69-5Relevant academic research and scientific papers
Asymmetric synthesis of protected β-substituted and β,β-disubstituted β-amino acids bearing branched hydroxyalkyl side chains and of protected 1,3-amino alcohols with three contiguous stereogenic centers from allylic sulfoximines and aldehydes
Gais, Hans-Joachim,Loo, Ralf,Roder, Daniel,Das, Parthasarathi,Raabe, Gerhard
, p. 1500 - 1526 (2007/10/03)
We describe a new method for the asymmetric synthesis, from allylic sulfoximines and aldehydes, of N,O-protected, cyclic and acyclic, β-substituted and β,β-disubstituted δ-hydroxy-β-amino acids and of N,O-protected 1,3-amino alcohols, both possessing three contiguous stereogenic centers. Treatment of enantiomerically pure, acyclic allylic sulfoximines with aldehydes after successive lithiation and titanation afforded sulfonimidoyl-substituted homoallylic alcohols with high regio- and diastereoselectivities. Diastereomerically pure, cyclic, sulfonimidoyl-substituted homoallylic alcohols were synthesized in a similar manner from the corresponding enantiomerically pure, cyclic allylic sulfoximines and isobutyraldehyde. A highly diastereoselective amination of the sulfonimidoyl-substituted homoallylic alcohols with the generation of secondary and tertiary C atoms and formation of the sulfonimidoyl-substituted, protected 1,3-amino alcohols (oxazinones) was achieved by the carbamate method, through cyclization of the corresponding carbamates after their lithiation with nBuLi. The sulfonimidoyl-substituted, monocyclic and bicyclic oxazinones were converted into protected, acyclic and cyclic, β-substituted and β,β-disubstituted β-amino acids and protected 1,3-amino alcohols by two different routes: the carbanion route and the substitution route. The carbanion route involves: (1) a double lithiation of the protected β-amino sulfoximines, (2) treatment of the dilithiated sulfoximines with electrophiles, and (3) reductive removal of the sulfonimidoyl group. By the carbanion route, double lithiation of the sulfonimidoyl-substituted oxazinones with nBuLi gave the corresponding dilithium salts, which reacted readily with a number of electrophiles to give the corresponding α-substituted sulfoximines in good yields. Reduction of the sulfoximines with Raney nickel afforded the corresponding protected monocyclic and bicyclic 1,3-amino alcohols and the protected acyclic and cyclic β-amino acids in good yields. The substitution route involves: (1) a facile substitution of the sulfonimidoyl group by a Cl atom, and (2) a substitution of the Cl atom of the protected β-amino chlorides by a cyano group. Treatment of the sulfoximines with ClCO2Me readily afforded the corresponding β-amino chlorides in good yields, and so treatment of alkyl sulfoximines with chloroformates seems to be a general method for the replacement of an N-methylsulfonimidoyl group by a Cl atom. Introduction of a cyano group was achieved through treatment of chlorides with NaCN, which gave the corresponding β-amino nitriles in good yields. Finally, hydrolysis of the nitriles afforded the protected acyclic and cyclic, β-substituted and β,β-disubstituted β-amino acids. Treatment of the protected β-amino sulfoximines with ClCO2Me gave - besides the corresponding chlorides - methyl (S)-N-phenyl-sulfinylcarbamate with ≥ 99% ee in good yield. Treatment of the sulfinamide with MeMgCl afforded (S)-methyl phenyl sulfoxide with 97% ee, and this could be converted with complete retention of configuration into (S)-N,S-dimethyl-S-phenylsulfoximine, the starting material for the synthesis of the allylic sulfoximines used in this work. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).
Regio- and enantioselective substitution of primary endocyclic allylic sulfoximines with organocopper and organocuprate reagents. The importance of iodide for the allylic substitution with organocopper compounds
Gais, Hans-Joachim,Müller, Harald,Bund, J?rg,Scommoda, Matthias,Brandt, Jochen,Raabe, Gerhard
, p. 2453 - 2466 (2007/10/02)
The endocyclic N-substituted allylic sulfoximines 17-20 and 26 were synthesized from the corresponding cycloalkanones and the various (S)-5-(lithiomethyl)-S-phenylsulfoximines in enantiomerically pure form in yields of 60-70% in a process involving the isomerization of the intermediate vinylic sulfoximines. Desilylation of 26 gave the parent N-H sulfoximine 27 from which the N-sulfonylsulfoximines 28 and 29 were prepared. The X-ray crystal structure of 28 was determined. The allylic sulfoximines 17-20 and 26-29 did not racemize or rearrange thermally to the corresponding allylic sulfinamides. Reaction of the allylic sulfoximines 18, 28, and 29 with the organocuprate reagents 2/LiI, 35/LiI, and 47/LiI led with α-selectivities of 92:8 to 99:1 to the endocyclic alkenes 39 in good to high yields. Reaction of 17-20, 28, and 29 with the organocopper reagents 5/LiI, 30/LiI, 31/LiI, 32/LiI, 33/LiI, 34/LiI, and 37/LiI in the presence of BF3 resulted in the formation of the exocyclic alkenes 38, 41, 43, and 45, respectively, in good to high yields with γ-selectivities of 80:20 to 99:1. The sulfonimidoyl group imparts asymmetric induction to the substitution in the range of 27-90% ee. The (S)-sulfonimidoyl group leads to a preferential bond formation from the si side of the double bond. From the sulfoximines 18 and 26-29 the N-methylsulfoximine 18 and the N-tosylsulfoximine 28 showed the highest and lowest reactivity with the butylcopper reagent 32/LiI in the presence of BF3, respectively, while in the absence of BF3 only 29 reacted. The Lewis acid most likely serves to activate the N-methyl- and N-tosylsulfoximines or intermediates thereof through coordination at the sulfonimidoyl and sulfonyl group. Reaction of the sulfoximines 18 and 29 with pure Me3SiCH2Cu (34) revealed a strong rate acceleration by LiI and an even stronger one by Bu4NI. This points to the existence of a heteroleptic cuprate or a related compound as reactive species. In substitutions with the Yamamoto reagents RCu/MX/BF3, the halide is important and a reaction between RCu and BF3 does not have, at least in the case of allylic sulfoximines, to be invoked. In reactions of 17-20 besides the alkenes, the sulfinamide ent-4 was formed with an ee value of 97% in high yield with retention of configuration. The absolute configuration of the exocyclic alkenes 38, 41, and 45 was determined by ozonolysis to the corresponding cycloalkanones followed by their conversion to the corresponding lactones and/or CD measurement of the former.
