The Conversion of Carbonyl Compounds into Pentadienylamines by a Julia-Kocienski Olefination Procedure

Abstract

Julia-Kocienski olefination has been successfully employed to convert carbonyl compounds into the corresponding Boc-protected 1,3-pentadienyl amines in a C₄N homologation process. Good to excellent yields are achieved in THF using MHMDS as base to deprotonate the precursor 1-phenyl-1H-tetrazol-5-ylsulfone reagent. The nature of the metallic countercation dramatically affects the stereoselectivity of the newly formed alkene: good levels of 2E,4E-stereoselectivity are achieved using KHMDS whereas LiHMDS gives a predominance of the 2E,4Z-dienyl product.

Key words

1,3-pentadienyl amines - modified Julia olefination - alkenes - 1-phenyl-1H-tetrazol-5-yl sulfones

References and Notes

• 1 Dvorak CA. Schmitz WD. Poon DJ. Pryde DC. Lawson JP. Amos RA. Meyers AI. Angew. Chem. Int. Ed.  2000,  39:  1664 ; and references therein
• 2 Kingston DGI. Kolpak MX. LeFevre JW. Borup-Grochtmann I. J. Am. Chem. Soc.  1983,  105:  5106 
• 3 Maehr H. Leach M. Williams TH. Blount JF. Can. J. Chem.  1980,  58:  501 
• 4 Mori T. Takahashi K. Kashiwabara M. Uemura D. Katayama C. Iwadare S. Shizuri I. Mitomo R. Nakano F. Matsuzaki A. Tetrahedron Lett.  1985,  26:  1073 
• 5 Takahashi K. Kawabata M. Uemura D. Iwadare S. Mitomo R. Nakano F. Matsuzaki A. Tetrahedron Lett.  1985,  26:  1077 
• 6a Ryu G. Kim S.-K. J. Antibiot.  1999,  52:  193 
• 6b Otani T. Yoshida K.-I. Kubota H. Kawai S. Ito S. Hori H. Ishiyama T. Oki T. J. Antibiot.  2000,  53:  1397 
• 6c Manam RR. Teisan S. White DJ. Nicholson B. Grodberg J. Neuteboom STC. Lam KS. Mosca DA. Lloyd GK. Potts BCM. J. Nat. Prod.  2005,  68:  240 
• 7a Papillon JPN. Taylor RJK. Org. Lett.  2000,  2:  1987 
• 7b Papillon JPN. Taylor RJK. Abstracts of Papers, 222nd Meeting of the American Chemical Society, Chicago IL, Aug 26-30, 2001   American Chemical Society; Washington DC: 2001. 
• 7c Papillon JPN. Taylor RJK. Org. Lett.  2002,  4:  119 
• 7d See also: Webb MR. Donald C. Taylor RJK. Tetrahedron Lett.  2006,  47:  549 
• 8 Connell RD. Helquist P. Åkermark B. J. Org. Chem.  1989,  54:  3359 ; this group also developed the phthalimide variant of reagent 8.
• 9 Baudin JB. Hareau BG. Julia SA. Ruel O. Tetrahedron Lett.  1991,  32:  1175 
• 10a Blakemore PR. Cole WJ. Kocienski PJ. Morley A. Synlett  1998,  26 
• 10b Kocienski PJ. Bell A. Blakemore PR. Synlett  2000,  365 
• 10c See also: Pospisil J. Markó IE. Org. Lett.  2006,  8:  5983 
• 11 For a review of the MJO, see: Blakemore PR. J. Chem. Soc., Perkin Trans. 1  2002,  2563 ; and references therein
• For recent applications in natural product synthesis, see:
• 12a trans-Vaccenic acid: Duffy PE. Quinn SM. Roche HM. Evans P. Tetrahedron  2006,  62:  4838 
• 12b [(-)-Sagittamide A: Lievens SC. Molinski TF. J. Am. Chem. Soc.  2006,  128:  11764 
• 12c Piericidin A1 and B1: Schnermann MJ. Romero FA. Hwang I. Nakamaru-Ogiso E. Yagi T. Boger DL. J. Am. Chem. Soc.  2006,  128:  11799 
• 12d Iejimalide B: Fürstner A. Aïssa C. Chevrier C. Teply F. Nevado C. Tremblay M. Angew. Chem. Int. Ed.  2006,  45:  5832 
• 12e Cylindramide: Cramer N. Buchweitz M. Laschat S. Frey W. Baro A. Mathieu D. Richter C. Schwalbe H. Chem. Eur. J.  2006,  12:  2488 
• 12f Macrolide FD-891: Garcia-Fortanet J. Murga M. Carda J. Marco JA. Matesanz R. Diaz JF. Barasoain I. Chem. Eur. J.  2007,  13:  5060 
• 13a Takano D. Nagamitsu T. Ui H. Shiomi K. Yamaguchi Y. Masuma R. Kuwajima I. Omura S. Org. Lett.  2001,  3:  2289 
• 13b Schultz HS. Freyermuth HB. Buc SR. J. Org. Chem.  1963,  28:  1140 
• 15 Hilpert H. Wirz B. Tetrahedron  2001,  57:  681 

14

Preparation of tert -Butyl ( E )-4-(1-Phenyl-1 H -tetrazol-5-ylsulfonyl)but-2-enyl Carbamate (11) To a solution of the sulfide 10 (7 g, 15.6 mmol) and Mo₇O_{24 (}NH₄)₆˙4H₂O (5.8 g, 4.7 mmol) in MeOH (130 mL) was added 30% aq H₂O₂ (48.3 mL, 468 mmol) at r.t. The solution was stirred for 1 h, and then sat. aq Na₂S₂O₇ solution was added to quench the excess of peroxide. After a stirring for 45 min at r.t., the reaction mixture was extracted with EtOAc (3 × 100 mL), dried (NaSO₄), and concentrated in vacuo; purification by silica flash column chromatography (PE-EtOAc, 1:1) gave the title sulfone 11 (5.6 g, 95%) as a white solid, mp 86 ˚C; R _f  = 0.56 (PE-EtOAc, 1:1). ^¹H NMR (400 MHz, CDCl₃): δ = 1.43 (s, 9 H, t-Bu), 3.77 (m, 2 H, CH₂-1), 4.41 (d, J = 7.5 Hz, 2 H, CH₂-4), 4.63 (br s, 1 H, NH), 5.29-6.04 (m, 1 H, H-2), 6.00 (dt, J = 15.0, 7.5 Hz, 1 H, H-3), 7.57-7.60 (m, 5 H, Ar). ^¹³C NMR (100 MHz, CDCl₃): δ = 28.7, 42.2, 59.5, 81.5, 114.5, 125.5, 130.0, 131.8, 133.3, 141.1, 153.4, 155.9. IR (neat): ν_max = 3356, 2978, 1709, 1502, 1347, 1249, 1155 cm^-¹. HRMS: m/z calcd for C₁₆H₂₁N₅O₄S [MH⁺]: 380.13925; found (CI): 380.1392 (0.1 ppm error).

16

The Julia-Kocienski olefination is normally trans-selective due to the kinetically controlled and irreversible addition of metallated PT-sulfones to aldehydes preferentially generating anti-β-alkoxysulfones, which then undergo Smile rearrangement. [¹0] [¹¹] In the present study, it would appear that LiHMDS preferentially generates syn-β-alkoxysulfones resulting in a predominance of the E,Z-adducts. The reasons for this unexpected switch are not fully understood at the present time but further studies are in progress to shed light on this interesting observation.

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Preparation of 1-[ N -( tert -Butoxycarbonyl)amino]-5-phenylpenta-2,4-diene (12)
To as stirred solution of PT-sulfone 11 (45 mg, 0.12 mmol, 1.2 equiv) in THF (1.4 mL) was added LiHMDS (0.26 mL 1.0 M in THF, 0.26 mmol, 2.55 equiv), or KHMDS (0.52 mL, 0.5 M in toluene, 0.26 mmol, 2.55 equiv), at -78 ˚C. In the KHMDS case, 18-crown-6 (34 mg, 0.13 mmol, 1.2 equiv) was also present at the outset. After 1.5 h at the same temperature, the orange mixture was added to benzaldehyde (10.6 mg, 0.1 mmol, 1.0 equiv) in THF (0.9 mL) at -78 ˚C via cannula. The mixture was stirred at -78 ˚C for 1.5 h and then for 1 h at r.t. After quenching with brine (3 mL) and stirring at r.t. for 10 min, the aqueous layer was extracted with EtOAc (3 × 8 mL). The combined organic phases were dried over MgSO₄ and concentrated in vacuo. Purification was performed via flash chromatography on SiO₂ using mixtures of PE and EtOAc as eluent to afford the product alkenes as mixtures of their 2E,4E/2E,4Z isomers (ratio was determined by ^¹H NMR spectroscopy).
Using KHMDS
72% (2E,4E/2E,4Z = 72:28); NMR data for major isomer 12 E,E were comparable to those published.⁸ Using LiHMDS
72% (2E,4E/2E,4Z = 13:87) as a pale yellow solid, R _f  = 0.71 (PE-EtOAc, 4:1); mp 42 ˚C. ^¹H NMR (400 MHz, CDCl₃; major isomer): δ = 1.43 (s, 9 H, t-Bu), 3.81 (m, 2 H, H-1), 4.58 (br s, 1 H, NH), 5.84 (dt, 1 H, J = 15.0, 5.5 Hz, H-2), 6.23 (t, 1 H, J = 11.6 Hz, H-4), 6.23 (t, 1 H, J = 11.5 Hz,
H-4), 6.42 (d, 1 H, J = 11.5 Hz, H-5), 6.69 (dddd, J = 15.0, 11.5, 2.5, 1.5 Hz, 1 H, H-3), 7.36-7.25 (m, 5 H, Ar). ^¹³C NMR (100 MHz, CDCl₃; major isomer): δ = 28.1, 42.2, 81.5, 127.9, 128.5, 128.7, 129.4, 129.6, 130.9, 132.9, 137.6, 156.1. IR (neat): ν_max = 3318, 2978, 1677, 1531, 1365, 1275, 1166, 995 cm^-¹. HRMS: m/z calcd for C₁₆H₂₁NNaO₂ [MNa]⁺: 282.1470; found: 282.1465 (3.5 ppm error)].

18

All novel compounds were fully characterised (sometimes as E,E/E,Z mixtures) including confirmation by high-field NMR and HRMS.