Sulfinamides catalysts

While most successful asymmetric organocatalytic imine reduction methodologies are limited to N-aryl imines. Sun et al. reported in 2008 that a new chiral sulfinamide catalyst 90 derived from L-proline is highly efficient for the reduction... 

Catalyst 41 (Fig. 29.29) is based on a sulfmyl imine, with the stereogenic center at the sulfinamide group. The best catalyst in this series, 41a, gave 94% ee in the hydrogenation of substrate 1 [54], The catalyst has low activity, with 5 mol% catalyst being required. 

It is also known (Mikolajczyk et al., 1976) that treatment of an optically active sulfinamide with an alcohol in the presence of two moles of strong acid as catalyst results in the formation of optically active sulfinate esters of inverted configuration (152), although the degree of stereoselectivity depends on the... 

In 1995 Pyne and Dong95 found that the ally lie sulfoximine 165 underwent a facile and completely regioselective and efficient rearrangement to the allylic sulfinamide 166 in the presence of tetrakis(triphenylphosphine)palladium(0) ((PPh3)4Pd) catalyst (5 mol%) at room temperature. Mild base hydrolysis of the reaction mixture (10% aqueous sodium hydroxide/methanol, 1 10, room temperature, 2 h) gave pure sulfonamide 167 after purification by column chromatography (silica gel) in 90% overall yield. 

Sulfinamide 46, developed by the same group, represents the most recent addition to this family. Here, the original formyl group of the proline derived catalyst 16 was replaced by the t BuSO moiety, which resulted in high enantio selectivities (<97% ee at 0 °C with 10mol% catalyst loading Table 4.10) [Ilf]. The striking feature of this catalyst is its efficiency with imines derived from nonaro matic amines, namely, benzyl, allyl, propyl, isobutyl, and p methoxybenzyl amine (Table 4.10), which renders 46 superior to 43 and dwarfs other catalysts (e.g., 16,19, and 45). Needless to say, this new feature broadens the synthetic arsenal beyond the N aryl substrates and opens new synthetic avenues. In comparison, the valine derived catalyst 47 proved to be less efficient with imines derived from aromatic... 

From the rather limited data reported by Matsumura [10], Sun [11], and Zhang [17], the pipecolinic acid derived catalyst 20 and the sulfinamide 46 appear to exhibit the highest enantioselectivities, similar to those attained with Sigamide 35[12]. However, the substrate portfolio [12h[ explored with the latter catalyst is much broader (Tables 4.3 4.7) so that a rigorous comparison cannot be made at present. Further more, Sigamide has performed consistently well at the standard 5 mol% loading and in selected examples was shown to operate with the same efficiency even when as little as 1 mol% had been used. Most of the catalysts listed in Tables 4.1, 4.2... 

The catalyst must act as a Lewis base. The structural features of Kocovsky s catalysts (e.g., 35) are detailed right below Table 4.1 (a) Valine i Pr (optimized) (b) N Me (c) N CH—O (formyl) and (d) another anilide group in the molecule. Other catalysts share similar features, in some cases the formamide group can be replaced by a picolinyl (41 43) of sulfinamide group (46). Other functional groups that can be considered are, for example, imidazolyl (high affinity to Si), oxazolidinyl, N oxide, phosphine oxides, and so on. 

In addition to amines, hydrazines, ammonia and fe/t-butyl sulfinamide were explored and applied as coupling partners as well. In the presence of palladium catalysts, N-H free indoles and 2-aminoindoles were selectively produced (Scheme 2.171). 

Continuing their work on the previously reported magnetite-catalyzed N-alkylation of aryl amines [138], in 2011 Ramon and co-workers reported Ru(0H)3/Fe304-catalyzed A -alkylation reactions of poor nucleophilic amines/ amides, such as aromatic and heteroaromatic amines, sulfonamides, sulfinamides, and nitroarenes (Scheme 26) [139]. The catalyst could be easily removed from the reaction mixture by magnet and reused up to ten times, showing the high activity of the catalyst (1st, 99 % 10th, 93 %). 

In 2014, Guan and co-workers reported the direct synthesis of a-chiral tert-butanesulfinylamines from the reaction of racemic alcohols and Ellman s sulfinamide catalyzed by ruthenium (II) pincer catalyst 23 (Eq. 54) [176], providing an effective method for the synthesis of chiral amine derivatives. 

In 2016, Xu and coworker reported another TM-fee aerobic Al-alkylation method for anilines, some heteroarylamines, and sulfinamides with alcohols (Scheme 49) [209]. As described in their work, these amines are not effective substrates under anaerobic catalyst-free autocatalyzed conditions, so an oxidant has to be employed to initiate the reaction. Differing from Yao and Zhao s protocol by adding O2 to an argon atmosphere [208], they found that a catalytic amount of air is active enough to initiate the reaction. In addition to primary alcohols, secondary alcohols can also be used as the aUcyl source. In mechanistic studies, the authors observed that primary and secondary alcohols underwent different initiation processes, i.e., primary alcohols require the presence of the amine to facilitate the aerobic oxidation to... 

Cano R, Ramon DJ, Yus M (2011) Impregnated ruthenium on magnetite as a recyclable catalyst for the N-alkylation of amines, sulfonamides, sulfinamides, and nitroarenes using alcohols as electrophiles by a hydrogen autotransfer process. J Org Chem 76(14) 5547-5557... 

Li X, Li S, Xu Q et al (2016) Efficient and practical catalyst-free-like dehydrative Af-alkylation of amines and sulfinamides with alcohols initiated by aerobic oxidation of alcohols under air. Tetrahedron 72(2) 264-272... 

Chiral 2-pyridylsulfinamides (32) have been efficiently used as catalysts in the alkylation of aryl and alkyl aldehydes with diethylzinc providing the corresponding alcohols in excellent enantioselectivity. Diastereomeric sulfinamides possessing chirality at the carbon-bearing nitrogen and at the sulfur of the sulfinamide increased the enantioselectivity up to 99%. It was conclusively proved that chirality at the sulfur centre is mandatory for obtaining good enantioselectivity in the reaction. 

Ti(OEt)4 was used for several purposes like as a water scavenger, as a catalyst for imine condensation, and as a Lewis acid to provide an enhanced reaction rate and diastereomeric ratio. The reaction procedures included condensation of the ketones with N-tert-hutane sulfinamide by heating in tetrahydrofuran in the presence of 2 equivalents of Ti(OEt)4. After formation of the corresponding imines, the reaction mixture was cooled to —48°C and added to a solution of NaBH4 in THE at the same temperature. The corresponding a-branched amines were isolated with a high diastereomeric ratio from iV-/cr/-butanesulfinyl imines (Scheme 39.37). 

---