N-Benzyl-1,2,3,6-tetrahydropyridine

Reference Production of 3-benzyl-7-oxa-3-azabicyclo[4.1.0]heptaneAfter mixing 7.77 g (44.8 mmol) of General procedure: A mixture of urea hydrogen peroxide (UHP, 1.85 g, 19.6 mmol) in dry DCM (16 mL) was stirred at 5 C while a solution of trifluoroacetic anhydride (TFAA, 4.12 g, 2.74 mL, 19.6 mmol) in DCM (8 mL) was gradually added within 15 min. The resulting mixture was stirred at 0-2 for 1 h. A cold solution prepared from 6b (2.68 g, 14 mmol) and trifluoroacetic acid (TFA, 2.08 g, 18.2 mmol) in DCM (10 mL) was added at 2-6 C within 5 min. After stirring the resulting mixture at 0-3 C for 20 min, the temperature was reduced to -15 to -10 C by means of an ice-salt bath.A solution of Na2SO3 (1.52 g, 12 mmol) and K2CO3 (3.46 g, 25 mmol) in H2O (18 mL) was carefully added to the vigorously stirred mixture without allowing the temperature of the resulting mixture to raise above 10 C. After addition, the mixture was stirred for 2 min and a test of the aqueous (upper) layer with KI-starch paper displayed a negative result for the presence of peroxide. The organic phase was separated and the aqueous layer was extracted with DCM (2 x 10 mL). The combined organic phase was washed with NaHCO3 (7.5%, 8 mL), dried (Na2CO3), filtered and evaporated. The residue (3.6 g) was dissolved in MTBE (12 mL), filtered through a plug of silica gel 60 ( 40-63 mum, ~ 2 g) and evaporated to leave a product (2.82 g, 97%), which turned out to be pure enough for subsequent transformations. The product was further purified by bulb-to-bulb distillation in vacuo (1-2 mbar) at 130-150 C (air-bath temperature) to yield 7b (2.70 g, 93%), as a colourless oil.Step 1: To a solution of After mixing 5.0 g (28.9 mmol) of A mixture of trifluoroacetic acid (1.15 mol) in water (2000ML) was stirred at room temperature. 1, 2, 3, 6-Tetrahydro-l- (phenylmethyl)-pyridine (1.15 mol) was added dropwise to the mixture and the mixture was stirred at room temperature for 15 minutes. N-BROMOSUCCINIMIDE (1.4 mol) was added portionwise and the mixture was warmed to 30-35C over 1 hour. The reaction mixture was stirred for 30 minutes. Again N-bromosuccinimide (0.085 mol) was added portionwise and the mixture warmed to 35C. The reaction mixture was stirred overnight at room temperature and then decanted and added dropwise to a NAOH solution 20% (2000 ml). The mixture was stirred overnight at room temperature. The product was extracted with DCM (3x). The separated organic layer was dried, filtered and concentrated. , yielding 193 g of intermediate (78).A mixture of TFA (0.43 kg, 3.81 mol) in water (6.3 L) was stirred at room temperature to which was added dropwise compound 3 (3.65 mol) and the resulting mixture was stirred at 20 C for 1 hour. NBS (1.3 kg, 7.25 mol) was added portion wise, and the resulting mixture was warmed to 35 C and stirred overnight. After cooling to 20 C, the reaction mixture was slowly added to a 20% NaOH solution (7 L), stirred overnight at 20 C and the product was extracted with DCM (3 x 4 L). The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo to afford 4a (685.6 g) as a yellow oil. The crude 4a was added to a solution of maleic acid (417.8 g, 3.6 mol) in EtOH (6.6 L) and stirred for 48 hours to afford a slurry. The solid was filtered, washed with cold EtOH and dried at 45 C in vacuo to afford 4 (471 g) as maleic acid salt. To a stirring solution maleic acid salt of 4 (431 g) was suspended in DCM (1.5 L) and water (0.6 L) was added 2 N NaOH solution (about 1 L) slowly until pH 9-10. The organic layer was separated and the aqueous layer was re-extracted with DCM (2 x 0.6 L). The combined organic layers were washed with brine (0.6 L), dried (Na2SO4) and concentrated in vacuo to give 4 (251.7 g) as a light brown oil (42% yield). 1H NMR (400.0MHz, CDCl3): delta 2.00 (2 m, 2H), 2.18 (m, 1H), 2.29 (m, 1H), 2.66 (m, 1H), 2.97 (m, 1H), 3.18-3.24 (m, 2H), 3.40 (s, 2H), 6.98- 7.24 (m, 5H); MS: 190 ; MS Found: 191 ([M+1]+).3.36 g of 1-Benzyl-3, 6-dihydro-2H-pyridine (10.00 g, 57.72 mmol, 1.00 eq) was dissolved in water (190.00 mL) and trifluoroacetic acid (24.02 g, 210.68 mmol, 3.65 eq) at 25 C and stirred at this temperature for 1 hour. The mixture was then heated to 35 C and bromosuccinimide (20.55 g, 115.44 mmol, 2.00 eq) was added and then the mixed solution was stirred for 5 hours, cooled to 25 C, and sodium hydroxide (2.31 g, 57.72 mmol, 1.00 eq) and acetonitrile (50.00 mL) were added to the mixed solution and then the mixed solution was stirred for 12 hours and concentrated under reduced pressure to remove the solvent. The residue was extracted with ethyl acetate (500 mL * 2). The combined organic layers were concentrated under reduced pressure and the residue was purified by silica gel chromatography (silica, petroleum ether / ethyl acetate = 10/1, 3: 1) to deliver 4-benzyl-7-oxa-4-azabicyclo[4.1.0]heptane (5.00 g, 26.42 mmol, 45.77% yield) as a yellow solid.General procedure: was conducted by combining 1-dodecanol (0.2 mmol), [Rh(cod)OMe]2 (2 mol %), 3-OMeBzOH (4 mol %), and Xantphos (4 mol %) in 0.4 mL toluene and heating the solution to 90 C. (see reaction scheme below). The reaction continued for 24 h before analyzing the crude reaction mixture by gas chromatography using durene as an internal standard to determine the amount of 1-undecene, 1-undecane, and undecene isomers present in the reaction mixture. Gas chromatography analysis determined that only 1-undecane was present in the reaction mixture (10 mol % yield).General procedure: Examples 1A-1K utilized the general experimental procedure described above for Example 1, except that an acceptor (3 molar equivalents based on the primary alcohol) was used. Examples 1A-1K were conducted as single, individual experiments; results from each reaction are shown in Table 1 below. Surprisingly, Example 1K, which employed dimethylacrylamide as the acceptor, exhibited a dramatic and unexpected improvement to the selectivity of the reaction with respect to the C(n-1) olefin product, producing a 95% molar yield of the desired 1-undecene product, and only about 3 mol % of alkane and internal olefin byproducts. Moreover, Examples 1H-1J also demonstrated excellent selectivity, each having a yield of 1-undecene above 30%, using ethyl acrylate, t-butyl acrylate, and acrylamide, respectively.

Molecular Weight:173.25
XLogP3:2.4
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:2
Exact Mass:173.120449483
Monoisotopic Mass:173.120449483
Topological Polar Surface Area:3.2
Heavy Atom Count:13
Complexity:168
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes