N C-alkylation

The instability of polyacetylene is notorious, that is, it is easily oxidized in air at room temperature. On the other hand, the substituted polyacetylenes shown in Table 27 are much more stable96. In general, the stability of substituted polyacetylenes increases with increasing number and/or bulkiness of substituents -f-CH = C(n-alkyl)- < -fCH=CPh, -f CMe=C( -alkyl)+n < CH=C(t-Bu), -f-CMe= CfSiMes)- < -j-C(n-alkyl) = CPh-, -(-CC CPh. Especially, the polymers of aromatic disubstituted acetylenes (e.g., (CMe=CPh, -fCCl=CPh ) are extreme-... 

The percent nondistillable material was determined by using as an internal standard, an equal volume ixture of C to C n-alkyl-benzenes (See also reference 9). T-NMR spectra data were obtained as reported in reference (3). 

Fig. 4. Variation of In(cmc) versus hydrocarbon chain length at 25 °C for various surfactants in aqueous media (A) n-alkyl hexa-oxyethylene glycol monoethers [19]. (B) n-alkylsulfinyl alcohols [20], (C) n-alkyl glycosides [19], (D) n-alkyltrimethylammoniurn bromides in 0.5 M NaBr [17,21], (E) n-alkyl betaines [221, (F) alkyl sulfates in pure water [2]. (Redrawn with changes)...

Scheme 20.3.1. Synthetic organic reaction , a. bromation, b. Perkin reaction, c N-alkylation of amines, performed in the basic eutectic mixture lChCl/2Urea described by Shankarling s research group.

Alkylative cyclization is one of the important methods in organic synthesis for the construction of cyclic structures. According to this concept, any intramolecular one-step C—N bond formation (V-alkylation) can be termed as C—N alkylative cyclization. Based on the general mechanistic pathways, such reactions are mainly of two kinds. In the first case, intramolecular C-N bond formation takes place by replacement of a leaving group X and the cyclization can occur via both Sjvl and Sjv2 pathways (Figure 40.13). 

FIGURE 40.13. C—N alkylative cyclization via replacement of leaving group. 

Ghorai et al. reported on the synthesis of A -tosylazeti-dines 187 by the alkylative cyclization of the corresponding y-amino alcohol 186. The amino alcohol 186 can be prepared from different commercially available amino acids 185 via homologation. Tosylation of primary alcohol group of 186 followed by C N alkylation under refluxing condition afforded chiral azetidine 187 with good overall yield and excellent enantiomeric excess (Scheme 40.38). ... 

Lectka et al. reported on a practical methodology for the catalytic, asymmetric synthesis of (3-lactams 203. Compound 203 results from the reaction of ketenes (or derived zwitterionic enolates) 201 and imines 202 via C—N alkylative cyclization using benzoylquinine as a chiral catalyst and a proton sponge as the stoichiometric base with moder-ate-to-good yield and excellent diastereoselectivity and enantioselectivity (Scheme 40.41). " ... 

Nicotine is an another very popular pyrrolidine ring-containing natural product, and it was isolated for the first time firom the dried leaves of tobacco plants Nicotiana rus-tica and N. tabacum, in 1828. After the first synthesis of this alkaloid by Pictet and Rotschy in 1904, the synthesis of nicotine and its analogs became attractive field in organic synthesis. In 1999, Crooks and co-workers synthesized (5)-nornicotine 211 using C—N alkylative cyclization as the key step (Scheme 40.42). 2-Hydroxy-3-pinanone keti-mine 207 obtained from 2-hydroxy-3-pinanone 206,... 

Earlier in 2006, Bertrand and Wolfe reported on the synthesis of (-l-)-preussin starting from decanal 103 (Scheme 40.22). After seven steps, the key intermediate 108 was obtained in 97% ee and 30% overall yield. 108 underwent Pd-catalyzed C N alkylative cyclization to afford the pyrrolidine derivative 109 with excellent diastereoselectivity. Derivative 109 under lithium aluminum hydride (LAH) reduction followed by alkaline workup produced (+)-preussin 100 in excellent yield. 

Polyhydroxypyrrolidine aza-sugar was synthesized starting from tri-O-benzyl-D-glucal 221. After steps, amino monoacetate 222 was prepared and it underwent C—N alkylative cyclization by the treatment of triphenyl phosphine and diethyl azodicarboxylate (DEAD) to produce flie corresponding polyhydroxypyrrolidine 223 in 88% yield (Scheme 40.45). 

A Cu(OTf)2-mediated highly regioselective S v2-type ring opening followed by C N alkylative cyclization of alkyl and substimted A-tosylaziridines 228 with nitriles to synthesize substituted imidazolines 229 with moderate-to-good yields has been reported by Ghorai et al. (Scheme 40.48). "... 

Akiyama et al. reported on the chiral Br0nsted-acid-cat-alyzed aza-Diels-Alder reaction of aldimines 237 with Brassard s diene 238. After the C N alkylative cyclization, piperidinone derivatives 239 were formed with high yield and excellent enantioselectivity. " They used pyridinium salt of chiral phosphoric acid as the chiral Br0nsted acid (Scheme 40.52). 

Zhou et al. reported on the ring opening of A -Ts aziri-dines followed by C—N alkylative cyclization with aryl propargyl alcohols in the presence of BuOK to afford dihy-droxazine derivatives 272 in moderate-to-good yield.It was hydrogenated with TFA and EtaSiH to produce 3,5-disubstituted morpholine derivatives 273 with excellent yield and high diastereoselectivity (Scheme 40.60). 

Couty et al. the reported on the total synthesis of a pyr-rolizidine alkaloid, (—)-absouline 294, which was isolated from new Caledonian plants and shows modest antiviral activity. Starting from 2-cyanoazetidine 290, they synthesized A-Boc-protected aminopyirohdine 291 after three steps with high yield and stereoselectivity. Then, C N alkylative cyclization was performed on 291 in the presence of triphenylphosphine to afford A-Boc-protected pyrrolizidine 292, which after deprotection followed by AA -dicyclohexylcarbodiimide (DCC) coupling with ( )-/ -methoxy cinnamic acid 293 afforded the alkaloid (—)-absouline 294 with good overall yield (Scheme 40.65). 

Gallagher et al. reported on various IV-heterocycle construction via cyclic sulfamides. Using this strategy, they synthesized enantiopure 1,4-benzoxazine 311, which was the precursor of the blockbuster antibiotic levolloxacin 312 (Scheme 40.67). Starting from Boc-protected amino alcohol 305, sulfamidate 306 was prepared using RuCU and NaI04. 306 was treated with halo phenol 308 followed by acidic hydrolysis to afford amino ether 310. The compound 310 underwent Pd-catalyzed C—N alkylative cyclization to produce benzoxazine 311, which was the potential precursor from which Levolloxacin 312 can be synthesized. 

C 2-C n alkyl 7- to 12-mole ethoxylates acetate or trimeth-ylsilyl derivatives ethoxy distribution up to the 18 ethoxylate... 

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