Butyl vinyl ether, cycloaddition with

Di- and trisubstituted nitroalkenes tethered to dipolarophiles (unsaturated esters, nitriles) undergo tandem [4+2]/[3+2] cycloadditions with 2,3-dimethyl-2-butene or butyl vinyl ether in the presence of Lewis acids (Eq. 8.112). For the dimethylene tether, the E-configuration of the dipolarophile is preferred, and the products arise selectively from a syn-endo pathway.177... 

A common method to synthesize pyridazines remains the inverse electron-demand Diels-Alder cycloaddition of 1,2,4,5-tetrazines with electron rich dienophiles. [4 + 2]-Cycloadditions of disubstituted 1,2,4,5-tetrazine 152 with butyl vinyl ether, acrylamide, phenylacetylene, and some enamines were performed to obtain fully substituted pyridazines 153 . This reaction was accelerated by electron withdrawing groups, and is slowed by electron donating groups, R1 and R2on the tetrazine. 

Inspired by the previous results, Leighton et al. reported the enantioselective [3 + 2] acylhydrazone-enol ether cycloaddition reaction by employing the same pseudoephedrine-based chiral silane. The pyrazohdine product was obtained in 61% yield with 6 1 dr and 77% ee in 24 h. The use of tert-butyl vinyl ether led to an improvement in both diastereoselectivity and enantioselectivity as shown in Scheme 34 [108]. 

The inverse-electron demand 1,3-dipolar cycloaddition has also been pursued with other Ti(IV) complexes (364). The cycloaddition reaction of C,Al-diphenyl nitrone to ferf-butyl vinyl ether catalyzed by different bidentate C2-symmetrical ligands gave moderate to good diastereoselectivity, and up to 41% ee was achieved. 

Both reactivity and selectivity decreased with increasing steric bulk of alkyl group on the vinyl ether (Et> -Pr> -Bu /-Bu), and tert-butyl vinyl ether was completely unreactive. The cycloaddition of ethyl vinyl ether with a wide variety of oc, 3-unsaturated aldehydes bearing aliphatic and aromatic P-substituents proceeded with high selectivity (>95% de, 89-98% ee). Only 5 mol% of catalyst were necessary except in the case of sterically more demanding substituents (R = i-Pr, Ar) that required 10 mol% of catalyst loading. Substitution could also be introduced in the a-position of the unsaturated aldehyde, and cycloadducts were obtained with similar high selectivities.26... 

As an extension of this work, photoinduced [2+2]-cycloadditions of 1-acetylisatin (13) with cyclic enolethers (furan, benzofuran, 2-phenylfuran, 8-methoxypsoralen), and acyclic enolethers (//-butyl vinyl ether and vinyl acetate) were investigated which afforded the spiro-oxetanes in high yields (82-96%) and with high regio- and diastereoselectivity (Sch. 4) [19]. Treatment of the furan-derived oxetane 15 with acid resulted in oxetane ring opening and yielded the 3-(furan-3-yl)indole derivative 16. 

A prototype cycloaddition involving a zwitterionic intermediate is the reaction of -butyl vinyl ether with tetracyanoethene, as shown in Eq. (5-33) [94-98]. 

Subsequent studies on the thermolysis of 1,2,3-selenadiazole 16 (n = Z) in the presence of a variety of alkenes (methyl acrylate, acrylonitrile, methyl vinyl ketone, methyl methacrylate, methyl 2-butenoic acid, butyl vinyl ether, and 1-octene) also afforded cycloadducts 17, in 12-76% yield with the same regiochemistry as observed for cycloadditions with 14 <2000JOM488>. Analogous cycloadditions with methyl derivatives of 16 (n = Z) as well as 16 ( = 1, 3, and 4) and ethyl acrylate was also observed in yields of 35-76% (Table 1). In addition to the cycloadduct. 

Thermochemical studies on the reaction between anthracene and TCNE in various solvents show that solvent-dependent changes in reactivity are largely determined by changes in the enthalpies of solvation of the reactants. The same is trae for the [2 + 2] cycloadditions between TCNE and n-butyl vinyl ether, and TCNE with trans-P-methyl-p-methoxystyrene. Experimental values for heats of solution and heats of sublimation of reactants allow one to calculate enthalpies of solvation of the reactants in dif-... 

Denmark and Marcin showed that 2,2-disubstituted 1-nitroalkenes undergo facile MAD-promoted [4 -r 2] cycloaddition with n-butyl vinyl ether in toluene at 0 °C to give cyclic nitronates as anomeric mixtures in good yield [173]. This method is a promising route to the stereoselective synthesis of disubstituted pyrrolidines and can thus be applied to the synthesis of the biologically active pyrrolidine alkaloid, mesembrine (Sch. 134). 

The aza Diels-Alder reactions of a, ff-unsaturated sulfinimines (140) represent a very efficient approach to enantiopure dihydro- and tetrahydropyridines (141) (Scheme 8.34, Table 8.11) for a reasonable reaction rate the 1-aza-l,3-butadiene moiety 140 must carry an electron-withdrawing group at the 3-position [65]. The compounds are accessible in only three steps starting from commercially available substrates. Thus, the enantiopure 1-aza-l,3-butadiene can be prepared from the enantiopure menthyl sulfinate with lithium hexamethyldisilazide followed by addition of acetic acid and an a, -unsaturated aldehyde. The cycloadditions of sulfinimines such as 140 run under mild conditions with high yields and excellent endo-selectivity in most cases when high pressure is applied. In these reactions two endo and two exo transition structures namely syn and anti to the sulfoxide moiety should be discussed. The cycloaddition of 140 and t-butyl vinyl ether was performed under various pressures ranging from 0.2 to 1.2 GPa. 

Markd and co-workers reported low levels of stereocontrol in the cycloaddition of 3-methoxycarbonyl-2-pyrone and butyl vinyl ether when TADDOL ligands are used in conjunction with YbfOTOj. ... 

Matsumoto and Kuroda presented a short and elegant synthesis for an ailatoxin Bi precursor by a [2 + 4]-cycloaddition with singlet oxygen (see Scheme 2.11). Rom 75, an intermediate was formed that reacted with iso-butyl vinyl ether (—> 76). Acid hydrolysis gave the free alcohol, which induced the formation of 77 (52). 

In 2011 the same research group described another efficient application of dicarbo Q lic acids 63 in the asymmetric inverse-electron-demand 1,3-dipolar cycloaddition (lED 1,3-DC) of C//-cyclic azomethine imines with t-butyl vinyl ether or vinylogous aza-enamines (synthesized from enals) (Scheme 24.23). This latter reaction, carried out without exclusion of moisture and air, gave cycloadducts regioisomeric to the products observed in the normal-electron-demand 1,3-dipolar cycloaddition (NED 1,3-DC) catalysed by Ti/binolate starting from the enals and for this reason the authors introduced the concept of lED umpolung 1,3-DC. 

The reaction can be applied to other olefinic substrates such as isopropenyl acetate and butyl vinyl ether. The reactions with cyclohex-2-enone give the corresponding cycloaddition products in 64 and 47% yields, respectively (Scheme 5.7). 

The reaction of a,co-diyne with monoene instead of monoyne also gave an aromatic compound (Scheme 5.4) [9], The reaction included cleavage of a C—O bond. Diyne 7 reacted with 50 equiv of 2,3-dihydrofuran to give aromatic alcohol 8 in 97% yield. Acyclic vinyl ether such as n-butyl vinyl ether could be used in place of 2,3-dihydrofuran. The reaction of 7 with 25 equiv of n-butyl vinyl ether gave 9 and 10. The combined yield was nearly quantitative. n-Butyl vinyl ether acted as an acetylene equivalent when the reaction gave 9. Based on this result, an enol ether could be used as an acetylene equivalent in Rh-catalyzed [2 -j- 2 -j- 2] cycloaddition [11]. 

Recently, Maruoka and coworkers have also developed an asymmetric inverse electron demand 1,3-dipolar cycloaddition of C,A -cyclic azomethine imines with fort-butyl vinyl ether catalyzed by a newly developed axially chiral dicarboxylic acid having diarylmethyl groups at the 3,3 -positions (Scheme 7.7) [18]. Based on this finding, the concept of the inverse electron demand umpolung 1,3-dipolar cycloaddition was introduced as a strategy for switching the regioselectivity of the cycloaddition from that of the titanium BINOLate-catalyzed normal electron demand 1,3-dipolar cycloaddition with enals (Table 7.3) by... 

SCHEME 7.7 Asymmetric inverse electron demand 1,3-dipolar cycloaddition of C.Al-cyclic azomethine imines with fert-butyl vinyl ether. 

FIGURE 7.4 Relationship between the ionic radius of the lanthanoid metals and the enantio- or diastereoselectivities for the cycloadditions of 2-benzopyrylium-4-olate with butyl vinyl ether catalyzed by chiral (45, 55)-PyBOX, 5-Ph2-M(OTf)3 complexes. 

In an analogous study by Meske, the impact of various oxazaborolidinone catalysts for the 1,3-dipolar cycloaddition reactions between acyclic nitrones and vinyl ethers was studied [31]. Both the diastereo- and the enantioselectivities obtained in this work were low. The highest enantioselectivity was obtained by the application of 100 mol% of the tert-butyl-substituted oxazaborolidinone catalyst 3d [27, 32] in the 1,3-dipolar cycloaddition reaction between nitrone la and ethyl vinyl ether 8a giving endo-9a and exo-9a in 42% and 27% isolated yield, respectively, with up to 20% ee for endo-9a as the best result (Scheme 6.10). 

A study of the regioselectivity of the 1,3-dipolar cycloaddition of aliphatic nitrile oxides with cinnamic acid esters has been published. AMI MO studies on the gas-phase 1,3-dipolar cycloaddition of 1,2,4-triazepine and formonitrile oxide show that the mechanism leading to the most stable adduct is concerted. An ab initio study of the regiochemistry of 1,3-dipolar cycloadditions of diazomethane and formonitrile oxide with ethene, propene, and methyl vinyl ether has been presented. The 1,3-dipolar cycloaddition of mesitonitrile oxide with 4,7-phenanthroline yields both mono-and bis-adducts. Alkynyl(phenyl)iodonium triflates undergo 2 - - 3-cycloaddition with ethyl diazoacetate, Ai-f-butyl-a-phenyl nitrone and f-butyl nitrile oxide to produce substituted pyrroles, dihydroisoxazoles, and isoxazoles respectively." 2/3-Vinyl-franwoctahydro-l,3-benzoxazine (43) undergoes 1,3-dipolar cycloaddition with nitrile oxides with high diastereoselectivity (90% de) (Scheme IS)." " ... 

Cycloadditions in which 1,2-dithietes acted formally as dienes are among the most typical reactions of 1,2-dithietes. The dithiete 144 is highly reactive and capable of reactions even with simple alkenes and alkynes (60JA1515 61JA3434,61JA3438). Thus, 144 reacted with acetylene to form 191 and 192 with the initial formation of 193, and with tetramethylethylene to give 194. Other [4 + 2] cycloadditions of 144 involved those with ethylene, cyclohexene, trans-stilbene, ethyl vinyl ether, butyl vinyl sulfide, 3-hexyne, and DMAD. 

Bauld and coworkers have examined the cation radical cycloadditions of 1,3-dienes with electron-rich alkenes and found that, under photosensitized electron-transfer conditions, [2 -i- 2] cycloaddition is in many cases favored over Diels-Alder addition. Thus, as illustrated in equation (30), 1, T-dicyclopentenyl (186) reacts with p-chloroethyl vinyl ether under electron transfer conditions to afford the cyclobutane adduct (187), which was cleaved to the cyclobutanol (188) in 70% yield upon treatment with n-butyl-iithium. Oxyanion-accelerated VCB rearrangement then provided (189) as a mixture of diastereomers in... 

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