2-Alkyl-4,4-dimethyl-2-oxazoline

There s no way -CH3 I can cover the complete naming system for organic compounds here but maybe what I ve presented will take the edge off when you see a molecule called 2-alkyl-4 4-dimethyl-2-oxazoline. Of course scientists never make things easy so you ll still see compounds called by their prefix naming convention. For example, we don t use the lUPAC system in naming isopropyl alcohol. 

Carbonyl alkylation and condensation reactions are always of great value in synthesis, and the formation of o-ANIS ALDEHYDE via 4,4-dimethyl-2-oxazoline, 2,2-DIMETHYL-3-PHENYLPROPION-ALDEHYDE via alkylation of the magnesio-enamine salt and threo-4-HYDROXY-3-PHENYL-2-HEPTANONE via a directed aldol... 

The Ugi group has designed a new class of convertible isocyanides, namely alkyl 2-isocyano-2-methylpropyl carbonates [7], prepared from commercially available 4,4-dimethyl-2-oxazoline. The Ugi-4CR of 11 afforded the expected products 12, which were converted into N-acyl a-amino acid esters 13 and N-acyl a-amino acids by in situ hydrolysis (Scheme 2.5) [7]. 

Coupling of R Br(Cl) with R2SnBu. 2 Alkyl halides couple with 2-(tributyl-stannyl-4,4-dimethyl-2-oxazoline (2) in the presence of this Pd catalyst (equation... 

Boron Azaenolates from Oxazolines. The reagent is useful for asymmetric aldol condensations of achiral oxazolines. Treatment of 2-ethyl-4-dimethyl-2-oxazoline with IpC2BOTf in the presence of a tertiary amine furnishes a boron azaenolate. Without isolation, treatment with an aldehyde in ether at —78 °C provides an alkylated oxazoline, which is hydrolyzed and converted to p-hydroxy ester via treatment with Diazomethane. Although the yields for the four-step sequence are only moderate, the anti selectivities of the hydroxy acids are excellent with enantioselec-tivities of 77-85% ee (eq 1). ... 

In the studies of the reactions of l-hydroxy-2-propanone and l-hydroxy-2-butanone and ammonium sulfide, despite four possible intermediates were predicted, only two intermediate compounds were tentatively identified by GC/MS in our study. The mass spectral data of these compounds showed very distinctive base peak p attem (Table I). These results agreed with results from previous study of five different 2-alkyl-2,4,5-trimethyl-2,5-dihydrooxazolines (7) which showed same mass spectral fragmentation pattern (m/z = 112) of same types of intermediate con5>ounds. Further study of GC/MS-CI results suggested their molecular weights and as the results, they were tentatively identified as 2-(1 -hydroxymethyl)-2,4-dimethyl-3-oxazoline, 2-( 1 -hydroxymethyl)-2,4-... 

Tohda et al. reported on the use of 2-primary alkyl 4,4-dimethyl-2-oxazolines in a crossed Claisen condensation (equation IS). The 2-primary alkyl oxazoline was treated with an acid anhydride in the presence of aluminum chloride and triethylamine in acetonitrile to give moderate yields (typically 50-65%) of the oxazoline derivative of a P-keto acid. The product can be monoalkylated selectively on the carbon adjacent to the heterocyclic ring, while the 2-oxazoline group can be converted into a variety of functional groups. 

Using analogous procedures and reaction conditions, the same authors have developed a valuable procedure for the direct synthesis of 2-alkyl-5,5-dimethyl-2-oxazolines 304 from carboxylic acids (Equation 53) <2003TL2331>. 

They appear to be more useful than bis(oxazolines) as ligands for palladium-catalyzed allylic alkylation with dimethyl malonate/BSA [N,0-bis(trimethylsilyl)acetamide]. 

Chiral oxazoline ligands 24a,bearing a chiral sulfinyl group provided enantiose-lectivity of (5)-2 with 88% or 55% ee, respectively, in the Pd-catalyzed alkylation of 1 with dimethyl malonate using [Pd(7r-allyl)Cl]2, BSA, and KOAc in dichloromethane... 

The synthesis of highly substituted /Sy-unsaturated ketones has been accomplished by reaction of allylmagnesium halides with 4,4-dimethyl-2-oxazolines. In the presence of a catalytic amount of chlorotris(triphenylphosphine)-rhodium(l), acyl chlorides and allyl tri-n-butyltin give the corresponding alkyl allyl ketone. A simple regiospecific synthesis of allyl ketones from allyl alcohols (Scheme 62) has been reported. ... 

Franzen and coworkers described a series of indole-phos-phine-oxazoline (IndPHOX) ligands, 231-238 (Scheme 35). The power of these ligands is demonstrated by the palladium-catalyzed asymmetric allylic alkylation of 1,3-diphe-nyl-2-propenyl acetate with dimethyl malonate with 98%... 

Asymmetric aldol reactions of a-keto esters (R-CO-COOMe R = Me, iBu, Ph) with methyl isocyanoacetate or N,N-dimethyl-a-isocyanoacetamide in the presence of 1 mol% of a chiral ferrocenylphosphine-gold(I) catalyst proceed enantiose-lectively (up to 90% cc) to give the corresponding oxazolines, which can be converted into optically active j8-alkyl-j8-hydroxyaspartic acid derivatives [1197]. Dehydration of the intermediate formamide to the corresponding isocyanide is accomplished in 97% yield with phosphoryl chloride at room temperature within 2h. 

Thanks to the fundamental studies of Tsuji, Trost, and others, palladium-catalyzed allylic substitution has become a versatile, widely used process in organic synthesis [40]. The search for efficient enantioselective catalysts for this class of reactions is an important goal of current research in this field [41]. It has been shown that chiral phosphine ligands can induce substantial enantiomeric excesses in Pd-catalyzed reactions of racemic or achiral allylic substrates with nucleophiles [42]. Recently, promising results have also been obtained with chiral bidentate nitrogen ligands [43]. We have found that palladium complexes of neutral aza-semicorrin or methylene-bis(oxazoline) ligands are effective catalysts for the enantioselective allylic alkylation of l,3-diphenyl-2-propenyl acetate or related substrates with dimethyl malonate (Schemes 18 [25,30] and 19 [44]). 

Palladium(II)-allyl complexes with these ligands were found to be effective catalysts for allylic alkylations with stabilized carbanions. Under standard conditions, using 2 mol% of catalyst and a mixture of BSA and catalytic amounts of KOAc as base, racemic l,3-diphenyl-2-propenyl acetate smoothly reacted with dimethyl malonate or acetylacetone to afford optically active substitution products (Table 1). The phosphinophenyl-oxazoline with a phenyl group at the stereogenic center proved to be the optimal ligand for this substrate. After a remarkably short reaction time, the desired substitution products were isolated in essentially quantitative yields with enantiomeric excess of 97-99%. These values exceed the selectivities previously obtained with other ligands [41-43]. 

Strong evidence for this model is provided by an elegant substrate-catalyzed single-turnover experiment presented by Sadow and coworkers [81]. The four-coordinate Cs-symmetric magnesium tris(oxazoline)borate alkyl complex [To MgMe] (To = tris(4,4-dimethyl-2-oxazolinyl)phenylborate) excludes additional ligands from the coordination sphere and is a competent precatalyst for the hydroamination of l-aminopent-4-enes. In line with the expectations furnished by the aforementioned systems, the reaction of l-amino-2,2-diphenylpent-4-ene follows the empirical rate law v = / obs[aminoalkene] [catalyst], with a KIE of... 

Similarly, Ohveira et al. have reported the synthesis of all four possible dia-stereomers of a component of the pheromone blend of the carpenter bee Xylocopa hirutissima via alkylation of 4,4-dimethyl-2-oxazoline derivatives [61] (Scheme 23). In this case, the carboxylic acid, allowing the formation of the 5-lactone, is masked as an oxazoline. The reaction of the anion of 2-ethyl-4,4-dimethyl-2-oxazoline 120 with iodide 121 gave compound 122 in 92 % yield, which was hydrolyzed and cyclized in one-pot under acidic conditions to provide a mixture of stereoisomers 123 and 124. 

Isocyano-2-methyl)-propyl-l-]-alkyl-carbonate [(2-Isocyano-2-methyl)-propyl-l-]-alkyl-carbonates (Ip) were developed by Lindhorst in collaboration with Ugi and have been referred to as the Lindhorst isocyanides [64], The synthesis of Ip and its analog are very simple (Scheme 7.44). Commercially available 4,4-dimethyl-2-oxazoline 135 can be deprotonated by "BuLi in anhydrous THF at -78° C and the resulting lithium alcoholate lo is captured with alkyl chloroformate (R = Me, Et, allyl, Bn) to provide 80% of the desired product as colorless crystals or oil (Scheme 7.44). It can be further purified by vacuum distillation. This one-step method offers several advantages (i) it does not involve phosgene or derivatives thereof, (ii) (p-isocyano-ethyl)-alkyl carbonates are stable and can be stored at room temperature, and (iii) it can be employed in a large-scale synthesis. 

---