Sml2-mediated

Scheme 2.162. Sml2-mediated domino reaction leading to bicyclic compounds 2-741.

Synthesis of funtionalized (Z)-fluoroalkene-type dipeptide isosteres (36) via Sml2-mediated reduction of y,y-difluoro-ot, -enoates 2.3.19. Reductive formation of fluoroolefins and subsequent conversion to diketopiperazine mimics (71). Nonpeptidic amide bond replacement... 

A. Otaka, J. Watanabe, A. Yukimasa, Y. Sasaki, H. Watanabe, T. Kinoshita, S. Oishi, H. Tamamura, N. Fujii, Sml2-mediated reduction of y,y-difluoro-a,/ -enoates with... 

In a manner similar to the Sml2-mediated homocoupling of enantiomerically pure (o-methylbenzaldehyde)-Cr(CO)3, the coupling reaction of the [methyl(o-tolylmethylene)amine]Cr(CO)3 complex 17 with SmE gives only ry -diamine 18 along with the reduced amine 19 (Equation (63)). ... 

In 1991, Inanaga achieved Sml2-mediated intermolecular cross-coupling between C=0 (ketones or aldehydes) and C=N by using 0-benzyl formaldoxime as a C=N component7 The reaction requires HMPA as a co-solvent and a suitable proton source such as /-butyl alcohol or ethylene glycol. A cross-coupling reaction between ketones and... 

Enantioselective synthesis of /3-amino alcohols by Sml2-mediated cross-pinacol coupling of the planar chiral iV-sulfonyl(ferrocenylidene)amine with ferrocene carboxaldehyde is achieved by facile reduction of the ferrocenyli-dene amine with Sml2, followed by enantioselective addition to the aldehyde (Equation (75)). ... 

Suggest a mechanism for the transformation of 1 into 2, which has been described as a "Sml2-promoted Grob-fragmentation reaction. followed by an in situ, stereocontrolled Sml2-mediated cyclisation "... 

S. Hanessian, C. Girard, and J. L. Chiara, A practical synthesis of 2-deoxy aldonolactones via a Sml2-mediated a-deoxygenation reaction, Tetrahedron Lett., 33 (1992) 573-576. 

Murakami, M. Masuda, H. Kawano, T. Nakamura, H. Ito, Y. Facile synthesis of vicinal di- and tricarbonyl compounds by Sml2-mediated double insertion of isocyanides into organic halides./. Org. Chem. 1991, 56,1-2. 

Inanaga showed that the presence of HMPA also accelerates the Barbier addition of alkyl halides to ketones and significantly improves the yield of the adducts.14 He also found that HMPA was a useful additive in the Sml2-mediated synthesis of lactones from bromo esters and ketones (Scheme 2.5). Since Inanaga s pioneering work, the Barbier reaction employing Sml2 HMPA... 

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). 

Many reactions mediated by Sml2 require the presence of a proton donor. The primary role of the proton donor is to quench alkoxides and carbanions produced as intermediates upon reduction or reductive coupling. The most commonly utilised proton donors are alcohols, glycols and water. It is now very clear, however, that proton donors can have a considerable impact on the efficiency of Sml2-mediated reactions and their regiochemical and stereochemical outcome. Often, even a modest change in the proton donor or its concentration can have a profound impact on product distributions. Two important examples of this phenomenon are discussed below. 

Inorganic salts are another important additive used to enhance the rate and selectivity of Sml2-mediated reactions. The use of inorganic additives can be traced to the seminal studies of Kagan during which he used catalytic amounts of ferric chloride to accelerate the coupling reactions of alkyl iodides and... 

Although the addition of catalytic amounts of transition metal complexes and salts results in clear benefits in many Sml2-mediated reactions, the mechanistic basis for their effect is unknown.54 Examination of the experimental procedures utilising catalytic amounts of Nil2 shows that, in most cases,... 

Ketone reduction using Sml2 can be highly diastereoselective. For example, in Corey s synthesis of the diterpenoid natural product atractyligenin, Sml2-mediated reduction of ketone 7 proceeded with complete diastereocontrol to give secondary alcohol 8 in 90% yield (Scheme 4.6).12... 

Keck recently applied the diastereoselective reduction of ( S-hydroxy ketones in an approach to the anti-tumour natural products epothilone A and B. Sml2-mediated reduction of p-hydroxy ketone 15 in THF-MeOH gave anti- 1,3-diol 16 in 94% yield and as a 96 4 mixture of diastereoisomers.18 Attempts to carry out the reduction using common hydride reducing agents gave 16 with poor levels of diastereoselectivity (Scheme 4.10).18... 

The fragmentation of cyclobutyl ketones has also been exploited in natural product synthesis. For example, Sorensen utilised the Sml2-mediated fragmentation of cyclobutyl ketone 27 in a synthesis of guanacastepene A and E ... 

Molander also extended his study to include the Sml2-mediated reduction of 2-acylaziridines, to give (1-amino ketones (Scheme 4.28).32... 

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