Asymmetric Synthesis of syn-alpha-Substituted beta-Amino Ketones by Using Sulfinimines and Prochiral Weinreb Amide Enolates

Link: Org Lett ASAP

Franklin A. Davis* and Minsoo Song

Department of Chemistry, Temple University, Philadelphia, Pennsylvania 19122

This paper detailed the use of Weinreb amide in stereoselective addition to sulfinimine. Stereoselectivity was controlled by stereochemistry of the sulfinyl group. The major stereochemistry of the product was found to be syn-isomer in excellent ratio.

The most optimal base was found to be LiHMDS in THF, and Et2O in only few cases. Both isomers of the amide products are useful building blocks in a variety of subsequent transformations as seen in schemes below.

As seen in Scheme 5, propyl amide 24 could effectively be used in place of the usual ethyl amide.

Highly Enantioselective Synthesis of gamma-Hydroxy-alpha,beta-acetylenic Esters Catalyzed by a beta-Sulfonamide Alcohol

Link: Org Lett ASAP

Li Lin, Xianxing Jiang, Weixia Liu, Li Qiu, Zhaoqing Xu, Jiangke Xu, Albert S. C. Chan, and Rui Wang*

State Key Laboratory of Applied Organic Chemistry, Institute of Biochemistry and Molecular Biology, Lanzhou University, Lanzhou 730000, China, and State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China

This is a study of three different chiral ligands and their effect in reaction of Ti-cat addition of organozinc reagent to aldehydes. The final result was enantioselective addition of methyl propiolate to aldehyde providing propargylic alcohol.

The ligands being looked at are:

It was found that there were differences in these three lignads, structure-wise and reactivity-wise. The reactivity difference was in term of the group being transferred to aldehyde. The result is summarized in the table below.

The difference was suspected to lie in the Lewis acidity of the chelating heteroatoms. In L*, the sulfonamide nitrogen and oxygen activated the titanium complex as a Lewis acid less than the oxygen atoms in TADDOL, which in term activated titanium less yet than oxygen atoms of BINOL. As a result, titanium complex is most Lewis acidic in BINOL and least in L*. This resulted in a more efficient transfer of ethyl grounp in the presence of BINOL than L*.

In addition both TADDOL and L* have blue oxygen atoms which were suspected to increase their Lewis basicity, which presumably offset the Lewis acidity of Ti-center when coordinated. In the most optimal conditions of acetylide addition to aldehydes using L*, the Lewis basicity was increase further by addition of DME as an additive. The most optimal conditions resulted in the following efficient transformation:

In addition to the example above, this methodology could be applied to a large number of aldehydes as summarized in the table below.

The proposed mechanism of this activation and transformation is summarized in the two-step sequence; first in the generation of alkynylzinc, and second in the addition of the alkynylzinc to aldehyde. All of these happened in one pot.