Cycloadditions scandium!!® triflate

Scandium triflate [33] is a more active catalyst than the lanthanide triflates and the cycloadditions can also be carried out in aqueous media (Chapter 4). The catalyst is easily recovered from the aqueous layer after the reaction is completed, and can be reused. Some of the cycloadditions carried out in DCM and catalyzed by Sc(OTf)3 are summarized in Table 3.2. 

Table 9.40 Chiral scandium triflate-catalyzed [3+2] cycloadditions of DPS-allenes to aldehydes.

Elsewhere, Faita et al. (438) bound the Evans chiral auxiliary to Wang or Merrifield resin for use as a dipolarophile in cycloadditions with C,N-diphenyl-nitrone. Yields on both resins are significantly reduced in comparison to the solution phase reaction (43-20% compared to 95%) but are unaffected by addition of magnesium perchlorate or scandium triflate catalyst. A one-pot process has been reported by Hinzen and Ley (439) that oxidizes secondary hydroxylamines to the... 

Novel and efficient [2 - - 3] cycloaddition reactions of NADH analogues with Q derivatives rather than the hydride-transfer reactions occur in the presence of scandium triflate, Sc(OTf)3, in MeCN to afford the cycloadducts (142). When 1 -benzyl-4-tert-butyl-1,4-dihydronicotinamide (t-BuBNAH) is used as an NADH analogue in the Sc +-catalyzed reaction with Q, the crystal structure of the cycloadduct was determined successfully, as shown in Fig. 53 (142). 

The [3-1-2] cycloaddition of aldehydes with a-substituted allenylsilanes is a powerful means of access to dihydrofurans [450 b]. Quite recently Evans et al. reported the first example of the catalytic asymmetric version using a chiral scandium triflate complex (Scheme 10.172) [480]. 

Non-chloroaluminate ILs, which are in general poor nucleophiles, have proven to be attractive alternative media for Lewis acid catalyzed reactions. ILs may have a reaction rate accelerating effect, and they may improve selectivity and facilitate catalyst recovery. This is the case for scandium triflate catalyzed Diels-Alder cycloaddition [8,9], three-component (aldehyde, aniline, triethylphosphite) synthesis of a-aminophosphonates [10], Claisen rearrangement and cyclization reactions [11], or Friedel-Crafts reactions [12, 13]. 

The ability of ionic liquids to dramatically improve the yields and selectivi-ties of reactions is clearly shown by the scandium-triflate-catalyzed Diels-Alder reaction.This cycloaddition usually has low turnover (TON < 10-20). Song studied this reaction in ionic liquids, which offered the possibility of recovering the catalyst. The cycloaddition between 1,4-naphthoquinone and 1,3-dimethylbutadiene catalyzed by a very small loading (0.2mol%) of Sc(OTf)3 in the standard [bmim][PF6] ionic liquid was used as a test reaction (Scheme 43). 

Iwasawa and coworkers discovered that mngsten penta-carbonyl facilitated indole ring formation from the appropriate aryl acetylenes (Scheme 1, equations 1 and 2) [1-3], The W(CO)j can be generated in situ by the irradiation of W(CO) in THF. The indolization in equation 2 is proposed to be a rare example of a 1,5-dipolar cycloaddition. Liang and colleagues observed that scandium triflate catalyzed the Friedel-Crafts cyclization of 5-(arylamino)pent-3-yn-2-ones to afford an array of indoles (equation 3) [4]. 

Highly enantiosele ctive annulation reactions of (tert-butyldiphenylsilyl)allenes with ethyl glyoxylate using bis(oxazolinyl)pyridine-scandium triflate complex was described [120]. This [3 + 2] cycloaddition gave the corresponding dihydrofurans in moderate to high yields with high enantioselectivities (Scheme 12.54). The vinyl-silane functionality was acylated in Friedel-Crafts reaction with acetyl chloride to produce a-alkoxyenone. 

Scandium Triflate-Catalyzed Rearrangement-Cycloaddition of 2,6-Diazasemibullvalenes and Diazo Compounds Synthesis of Triazabrexadienes... 

Scheme 6.6 Scandium triflate-catalyzed ring opening-rearrangement-cycloaddition of 2,6-diazasemibuUvalenes and diazo compounds...

Kerr and coworkers have also successfully reported the use of cobalt hexacarbonyl cyclopropanes in [3-1-2] cycloadditions with nitrones via a purported Nicholas-type reaction in the presence of scandium triflate (Sc(OTf)3) to afford a variety of oxazines in high yields (Scheme 10.9) [11]. 

Intriguingly, boron trifluoride, the Lewis acid of choice for the cobalt alkyne cyclopropane, did not give any of the cycloaddition product on reaction with an aldehyde. Instead optimization studies showed that a catalytic quantity of scandium triflate induced the reaction. Also, there are marked differences in the reactivity and stereocontrol achieved. In this case, electron-rich aldehydes give better yields and for the first time with a cobalt alkyne, good stereocontrol. Again, no reaction was seen at all without the activating cobalt group. 

Kerr reported that Yb(OTf)3 was the most efficient Lewis acid to catalyze the cycloaddition reaction. Although reports by Tang and coworkers showed that scandium triflate was able to catalyze the reaction with an increase in diastereo-selectivity and a lower catalyst loading [42]. In these examples the imines were synthesized prior to the reaction via a condensation between amines and aldehydes. The results showed that both electron-rich and electron-poor imines were successful in the cycloaddition reaction. The position of the substiment on the aryl groups affected the yield obtained, where the para-substituted imines were favored over the artfia-substituted imines as a result of steric interactions. 

Ma Y, Qian C. [2+2] Cycloaddition reactions of imines with alkynyl selenides catalyzed by scandium triflate. Tetrahedron Lett. 2000 41 945-947. 

Related to the nitrile oxide cycloadditions presented in Scheme 6.206 are 1,3-dipolar cycloaddition reactions of nitrones with alkenes leading to isoxazolidines. The group of Comes-Franchini has described cycloadditions of (Z)-a-phenyl-N-methylnitrone with allylic fluorides leading to enantiopure fluorine-containing isoxazolidines, and ultimately to amino polyols (Scheme 6.207) [374]. The reactions were carried out under solvent-free conditions in the presence of 5 mol% of either scandium(III) or indium(III) triflate. In the racemic series, an optimized 74% yield of an exo/endo mixture of cycloadducts was obtained within 15 min at 100 °C. In the case of the enantiopure allyl fluoride, a similar product distribution was achieved after 25 min at 100 °C. Reduction of the isoxazolidine cycloadducts with lithium aluminum hydride provided fluorinated enantiopure polyols of pharmaceutical interest possessing four stereocenters. 

In subsequent studies, methyl vinyl ketone (2.0 mmole) was chosen as the dienophile so as to determine the combined effect of the ionic liquid (2 mL) and the Lewis acids (0.2 and 0.5 wt%) upon the yield and selectivity. Without the Lewis acid catalyst, this system demonstrated a 52% conversion of the cyclopentadiene (2.2 mmol) in 1 h with the endojexo selectivity being 85/15. The cerium triflate-catalyzed reaction was quantitative in 5 min and the endo. exo selectivity was very good for this experiment as well (94 6, endo. exo). Also with the scandium or yttrium salts tested, reactions came to completion in a short time with high stereo-selection. Cerium, scandium and yttrium triflates are strong Lewis acids known to be quite effective catalysts in the cycloadditions of cyclopentadiene with acyclic aldehydes, ketones, quinones and cycloalkenones. These compounds are expected to act as strong Lewis acids because of their hard character and the electron-withdrawing triflate group. On the other hand, reaction times of 1 hour were required for... 

In recent years some work has been done to link oleochemicals with petrochemicals via oligomerization. One possibility is the Dids-Alder reaction of linoleic acid esters with dienophiles, for instance with quinones or ,/Tun saturated aldehydes and ketones [80]. Using scandium or copper triflates as catalysts the reaction can be carried out at very mild temperature conditions (25-40°C) with good yields (< 94%). For the first time in oleochemistry it was possible to carry out Diels-Alder cycloadditions with low catalyst concentrations instead of stoichiometric amounts of Lewis acids. The most successful way to recycle the catalyst was the successive extraction of the triflates with water. After removing the water and drying in vacuum the catalyst was used three times without any loss of yield. 

Harmata further developed this reaction by demonstrating that triisopropylsiloxyacrolein 79 could undergo [4+3] cycloadditions under scandium (111) triflate catalysis (Scheme 18.16) [22]. Not only was this reaction catalytic in Lewis acid, the cycloaddition yields with furan and cyclo-pentadiene were significantly improved, and the triisopro-pylsilyl group was completely transferred to yield a-siloxycycloadducts 80 and 81, respectively. The reaction... 

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