Sml2-promoted reduction

Scheme Sml2-promoted reductive coupling of optically pure tricarbonylchromium-complexed benzaldimines and ferrocenyl diimines...

Optically active chiral vicinal diamines are produced by Sml2-promoted reductive coupling of an imine derived from benzaldehyde and l-isopropyl-2-methoxyethylamine. Intermolecular coupling proceeds in a diastereoselective... 

Scheme 10 Mechanism for the Sml2-promoted reduction of the thiopyridine containing peptides and their coupling to carbonyl compounds...

A Sml2-promoted reductive deamination of methyl prolinate derivative 235 to a 5-aminoester, followed by spontaneous recyclization to lactam 236, was exploited in the synthesis of several lupine alkaloids (Scheme 69) <05JOC499>. 

First Sml2-promoted reduction of hydroxy sulfones. 

Scheme 7.44. Sml2-promoted domino reductive desulfuration/reductive coupling process of lactams 7-166 with an aldehyde.

A Sml2-induced reductive cyclization of (V-(alkylketo)pyrroles provided an entry into medium ring 1,2-annelated pyrroles <06EJO4989>. An oxidative radical alkylation of pyrroles with xanthates promoted by triethylborane provided access to a-(pyrrol-2-yl)carboxylic acid derivatives <06TL2517>. An oxidative coupling of pyrroles promoted by a hypervalent iodine(III) reagent provided bipyrroles directly <060L2007>. 

Although many early synthetic studies employed HMPA as a cosolvent, its mechanistic role remained unclear. Its role was later clarified by Molander, who studied the influence of HMPA concentration on the product distributions from the Sml2-mediated reductive cyclisations of unactivated olefinic ketones.16 The addition of HMPA was required to promote efficient ketyl-alkene cyclisation, and correlations between the concentration of HMPA, product ratios and diastereoselectivities were apparent (Scheme 2.6). In the absence of HMPA, attempted cyclisations led to the recovery of starting material 1, reduced side-product 3 and desired cyclisation product 2. Addition of 2 equiv of HMPA provided 2 and only a small fraction of 3. Further addition of HMPA (3-8 equiv) provided 2 exclusively (Scheme 2.6). 

The Sml2-promoted mechanism follows a pathway originally proposed for the Na-Hg reductions (Scheme 4.31). The exact role of DMPU is not clear, but rate enhancement may be due to lowering of the oxidation potential of Sml2. 

Another cyclization method towards synthesis of myo- inositols and chiro-inositols resulted from a Sml2-promoted intramolecular pinacol reaction. Treatment of dienes 34 and 35 with ozone produced a dialdehyde after reduction of the ozonide with dimethyl sulfide. Subsequent Sml2-mediated pinacol coupling gave the corresponding protected inositols as a mixture of diastereomers [89]. 

Scheme 3.36. Mechanism of Sml2-promoted reverse reductions.

Metal-promoted reductive p-elimination reactions in 1,2-difunctionalized substrates have been one of the most important means of generating C=KZ bonds [9]. In the past few years, a number of reductive elimination reactions of 1,2-difunctionalized compounds have been reported under various organometallic reagents, such as Sml2 [10], Zn [11], or In [12], In addition, those low-valent organometallic species exhibit excellent properties for sequential organic reactions and several examples have been described in which a metal-promoted ehmination reaction occurs as a step of a sequential process [13],... 

Intramolecular pinacol reduction. Sml2 can promote intramolecular reductive conpling of keto aldehydes to provide 2,3-dihydroxycyclopentanecarboxylates with marked diastereoselectivity.2... 

Some additives accelerate the pinacol coupling reactions. Addition of Me3SiCl to Sml2 also accelerates the pinacol coupling reactions of aliphatic ketones and aldehydes. Pinacol coupling reactions are also promoted with samarium metal and a Lewis acid such as Et2AlCl or MesSiCl. Coordination of such a Lewis acid to a carbonyl oxygen facilitates the one-electron reduction by samarium. 

The intramolecular coupling of an aldehyde and alkene at —78 °C, promoted by Sml2, in the presence of a ketone, has led to a tandem coupling-addition process. This reaction has proved to be synthetically very useful for the preparation of poly-oxygenated compounds (equation 139)523. This reductive coupling process may also be promoted in dry methanol,... 

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