Macmillan report

Unlike most enantio- and diastereoselective direct aldol processes, the enamine-catalyzed aldol reactions are also feasible with aldehyde donors. In a milestone paper, Northrup and MacMillan reported in 2002 that aldehyde-aldehyde aldol... 

The power of intramolecular Diels-Alder reactions have also been exploited in the synthesis of a number of natural products. MacMillan reported a concise and highly practical synthesis of solanpyrone D [51, 218] and Koskinen described an... 

MacMillan reported a short and effective synthesis of spiculisporic acid which elegantly exemplified his Mukaiyama-Michael addition of silyloxyfurans to a,P-unsatu-rated aldehydes [88], Robichaud and Tremblay augmented this in a formal synthesis of compactin [224], Within this report it was shown that low enantioselectivities were obtained in the conjugate addition to aCTolein. Use of p-silyl acrolein 177 circumvented this and gave butenohde 178 in 95% yield and 82% ee. Conversion of adduct 178 to the decaUn (179) in eight steps resulted in a formal synthesis (Scheme 71). 

Barnes and MacMillan reported (37) an investigation of this rearrangement using the epimeric ( —)-kaur-16-en-15-ols as models. The 15/i-ol (20) rearranged rapidly to 16-( — )-kaur-15-one (21) in mineral acid at room temperature whereas the 15a-ol (22) was stable under these conditions. The English workers proposed a 15 -> 16 hydride-shift mechanism on the basis of the... 

Subsequently, MacMillan reported the second-generation MacMillan s catalyst Sb for the Friedel-Crafts alkylation reaction of pyrrole to, form a,p-unsaturated aldehydes (Equation 10.15) [32]. 

In 2005 Kunz and MacMillan reported the use of 2-carbo gflic acid dihydroindole 38 as a directed electrostatic activation (DEA) catalyst for the cyclopropanation reaction of a,(3,-unsaturated aldehydes with stabilised sulfur ylides (Scheme 11.40). ... 

The first organocatalytic intermolecular asymmetric aldol reaction was reported by List and coworkers in 2000 [23]. The aldol reaction between acetone and a variety of aldehydes was accomplished in excellent yields and high levels of e-nantioselectivity. For example, the aldol product of the coupling with o-butyral-dehyde was formed in 97 % yield and 96 % ee ((1), Scheme 4.10). The remarkable levels of selectivity sparked massive interest in the field of proUne-catalysed aldol, Michael and Mannich reactions. Later that year MacMillan reported a phenylalanine-derived catalyst (35) for the Diels-Alder reaction of a-P-unsaturated aldehydes with up to 94 % ee ((2), Scheme 4.10) [24]. Many further applications of... 

In 2005, MacMillan reported an enantioselective organocatalytic intramolecular Diels-Alder reaction (IMDA) of a,p-unsaturated aldehyde and diene, as well as the application in the asymmetric synthesis of solanapyrone D (6), Scheme 3.1 [5]. Later, Danishefsky and Christmann individually reported the total synthesis of UCS1025A (9) by coupling reaction with MacMillan aldehyde (8) [6]. The malim-ide analogue 10 of the telomerase inhibitor UCS1025A (9) was also prepared by Christmann et al. by modified MacMillan s conditions (10 mol% catalyst loading in nitromethane, affording 74% yield and >99% ee after a sequence of recrystallization and oxidation). Scheme 3.2 [7]. 

Later in 2002, MacMillan reported the first organocatalytic enantioselective Diels-Alder reaction of dienes with a,P-unsaturated ketones 34, Scheme 3.10 [20]. 

Recently, MacMillan reported a nine-step enantioselective total synthesis of (+)-minflensine via the key step reaction of organocatalytic Diels-Alder-cascade cyclization. Scheme 3.43 [58],... 

In a similar approach, MacMillan reported an operationally simple procedure for the enantiocontrolled C-F bond formation. The enantiose-lective a-fluorination of aldehydes was based on the use of imidazolidinone I as the active catalyst. MacMillan proposed the use of M-fluorobenzene-sulfonimide 3 (NFSI) as a fluorinating agent (Seheme 18.5 B). A similar mechanism has been proposed for both ehlorination and fluorination with the MaeMillan eatalyst, in which the imidazolindinone enamine reacts with the halogen source, although this mechanism has not been proven... 

Nicewicz and MacMillan reported an elusive asymmetric intermolecular a-alkylation of aldehydes by elegantly merging Ru photoredox catalysis with chiral amine organocatalysis [30]. The reaction mechanism proposed for the synergistic catalysis is illustrated in Scheme 2. 

Just before Cho s report, Nagib and MacMillan reported a high-impact work on direct C—H trifluoromethylation of arenes by photoredox catalysis [79]. The use of [Ru(phen)3]Cl2 as photocatalyst and CF3SO2CI (18a) as a CF3 source enables the reaction with the broad scope with respect to the arenes, i.e., electron-rich/electron-deficient heteroarenes and unactivated arenes, in the absence of sacrificial electron... 

The first organocatalytic asymmetric carbon nucleophilic addition to enals was reported by MacMillan in 2001 [15]. MacMillan reported the first Friedel-Craft alkylation between N-substituted pyrroles and enals promoted by catalyst 7. The reaction renders the final compounds in good yields and enantioselectivities (Scheme 33.4). 

Despite this early success, it was not until 2006 that MacMillan reported the first highly enantioselective intermolecular aza-Michael addition to enals [51]. In this work, MacMillan reported the use of N-sUyloxycarbamates as nucleophiles. The N-O functionality would increase the nucleophilicity at the nitrogen center via the a-effect, while the carbamate functionality would decrease the basicity of the... 

Organo-SOMO catalysis was also applied to polyene cyclization. In 2010, MacMillan reported an enantioselective cyclization reaction of substrates 41 for accessing steroidal and terpenoidal frameworks. They used imidazolidinone 40 instead of catalyst 23, with the aid of copper(ll) triflate as the oxidant. The polyene cyclization took place smoothly, giving polycyclic systems 42 and even more complex compounds 43 or 44 in good yields and with high enantioselectivity and exclusive diastereoselectivity (Scheme 36.12) [18]. 

Since MacMillan reported the first chiral secondary amine catalyst for organocatalytic Diels-Alder reactions [6], intensive studies on the development of novel... 

In 2005, Mangion and MacMillan reported on the smart synthesis of two closely related natural compounds littora-lisone isolated from Verbena littoralis and brasoside (Scheme 11.25). ° These two syntheses were crucial for the expansion of organocatalysis because they highlighted the extraordinary potential of several organocatalytic methodologies. The key point for the synthesis of these molecules was the development of an intramolecular Michael addition. Using L-proline as catalyst, the substrate reacted under kinetic catalyst control to furnish the desired... 

MacMillan reported a photoredox catalyst induced arene trifluoromethylation approach emplo3dng triflylchloride as the CF3 source. In this instance, treatment of the parent C-H compound with a ruthenium(ii) or iridium(iii) catalyst under irradiation from a 26 W household lightbulb resulted in the direct trifluoromethylation of 5- and 6-membered heterocycles as well as benzenoid systems (Scheme 15.94). Again, as with other innate C-H methods, some examples did lead to the formation of regioisomers. 

Since the MacMillan report, organocatalytic Diels-Alder reactions in water have been further explored [107]. Reported by Hayashi et al. [108], asymmetric Diels-Alder reaction of ,p-unsaturated aldehydes with dienes, catalyzed by a chiral diarylprolinol silyl ether salt 39, could be scaled up to 20 mmol in water. The aqueous phase can be removed simply by decantation, and distillation affords the cycloadduct with high yields and selectivities. A typical example is seen in Scheme 6.19. 

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