Catalysts MacMillan

The MacMillan catalysts (42, 45), the Jorgensen catalyst (51), and proline itself can promote Michael additions by iminium ion formation with the acceptor enal or enone (A, Scheme 4.22). Secondary amines can also activate a carbonyl donor by enamine formation (Scheme 4.22, B) [36, 37]. 

C. MacMillan, /. Am. Chem. Soc. 2000, 122, 4243-4244. For the synthesis of polymer-bound derivatives of the MacMillan catalyst and applications in Diels-Alder reactions, see M. Benaglia, G. Celentano,... 

Recently, Overman, et al. reported an organocatalytic Diels-Alder reaction of 2-acetoxy-1,3 -butadiene 40 and acrolein (28f) by MacMillan catalyst, ent-30-HOTf, Scheme 3.11 [21], It was noteworthy to use water-saturated nitromethane as the reaction solvent. The adduct 41 was transformed to a tetracycle with the skeleton of the ring A-D of daphnicyclidin-Type alkaloids (42). 

Natural product synthesis is often seen as a test for novel synthetic methodologies or catalysts to confirm their general application and robustness. The Macmillan catalyst has been extensively used in the asymmetric synthesis of variously functionalised natural product targets, with various reaction types being employed (Figure 18.4). The reactions discussed herein... 

In addition to aromatic substrates, the MacMillan catalyst has been shown to be applicable for the all lation of ben lic substrates, as seen in the five-step synthesis of bisabolane sesquiterpene (R)-(—)-curcumene by Cozzi and coworkers. Using I as the HCl salt, the a-allg lated product was generated with excellent enantiocontrol (after reduction 95% yield, 94% ee). This route also allowed for the synthesis of a related compound, (/ )-(—)-erogorgiaene. ... 

The first organocatalytic enantioselective intramolecular aza-Michael reaction was reported by Takasu et al. [101] in 2003 (Scheme 11.27). The authors, based on iminium ion activation and using MacMillan catalysts [102], described the synthesis of tetrahydroisoquinolines in high yields, although with poor enantiocontrol and long reaction times. 

Banwell et al. synthesized these alkaloids by carrying out an intramolecular cyclization of 292 using the MacMillan catalyst (8), which gave them the rather unstable key intermediate 293 in good yield and reasonable enantioselectivity. Compound 293 was then transformed into 288, which could be converted further into the other natural analogues 289-291 (Scheme 65) (267). 

Preparation of (5)-6-bromo-8-(3-prenyl)-3a-(3-oxo-propyl)-3,3a,8,8a-tetrahydro-2//-pyrrolo[2,3-6)indole-l-carboxylic acid tert-butyl ester (222) from A -lO-BOC-l-prenyl-6-bromotryptamine (220), acrolein (213), and MacMillan catalyst 211A... 

The direct nucleophilic substitution of alcohols represents a valuable methodology for the preparation of a variety of derivatives, since water is the only byproduct of the transformation. In this context, Cozzi et al. have reported very recently an organocatalytic alkylation of aldehydes proceeding through an SNl-type reaction of alcohols. This very simple method to effect the enantioselective direct alkylation of a wide range of aldehydes with unfunctionalised alcohols was catalysed by MacMillan catalyst and provided good to high yields and enantioselectivities of up to 90% ee, as shown in Scheme 5.5. 

Benjamin List of the Max-Planck Institut, MuUieim employed Nat. Chem. 2009,1, 225) a MacMillan catalyst for the reductive cychzation of 26. Subsequent epimerization and Tishchenko hydride transfer then proceeded with high diastereoselectivity, leading directly to the liverwort-derived (+)-Ricciocarpin A 28. 

MacMillan catalyst 5 for the cycUzation of 18 to 19. It is impressive that ent-5 catalyzed the cychzation of 18 cleanly into the diastereomer of 19 in which both of the newly-created stereogenic centers were inverted. 

In 2010 Kotsuki [24] reported high-pressure studies on a difficult Diels-Alder reaction of furan and acrolein catalyzed by secondary and primary amines, for example, proline, phenylalanine, diphenylprolinol, and the MacMillan catalyst (Scheme 21.6). The best results in terms of yield were obtained with simple amino acids (proline and phenylalanine) under 8kbar but, unfortunately, were accompanied with very low ee. The use of lower pressure (2kbar) and prohne as a catalyst resulted in very low yield and an increase in enantioselectivily up to 21%. 

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