Zinc-Mediated Allylation Followed by Lactonization of Dialkyl 2-(3-Oxo-1,3-diarylpropyl)malonates: Construction of δ-Lactones with Multiple Stereocenters

Abstract

A variety of polysubstituted δ-lactones containing three or four stereocenters were prepared from various dialkyl 2-(3-oxo-1,3-diarylpropyl)malonates by a Barbier-type zinc-mediated allylation or cyclohexenylation of the keto group, followed by intramolecular lactonization/transesterification. The stereochemistry of the major isomers was confirmed by X-ray crystal structure analysis of representative compounds.

Key words

allylation - diastereoselectivity - lactones - stereoselective synthesis - zinc

• References and Notes


For selected reviews, see:
• 1a Collins I. J. Chem. Soc., Perkin Trans. 1 1999; 1377
• 1b Zhao W, Sun J. Synlett 2014; 25: 303
• 1c Kammerer C, Prestat G, Madec D, Poli G. Acc. Chem. Res. 2014; 47: 3439
• 1d Albrecht A, Albrecht Ł, Janecki T. Eur. J. Org. Chem. 2011; 2747
• 1e Geske GD, O’Neill JC, Blackwell HE. Chem. Soc. Rev. 2008; 37: 1432
• 1f For a selected review on super-statins, see: Časar Z. Curr. Org. Chem. 2010; 14: 816

For selected reviews, see:
• 2a Boucard V, Broustal G, Campagne JM. Eur. J. Org. Chem. 2007; 225
• 2b Florence GJ, Gardner NM, Paterson I. Nat. Prod. Rep. 2008; 25: 342
• 2c Brenna E, Fuganti C, Serra S. Tetrahedron: Asymmetry 2003; 14: 1
• 2d Seitz M, Reiser O. Curr. Opin. Chem. Biol. 2005; 9: 285
• 2e Ogliaruso M, Wolfe J. In: Synthesis of Lactones and Lactams . Wiley; Chichester: 1993
• 2f Koch SS. C, Chamberlin AR In Studies in Natural Products Chemistry . Vol. 16, Part J. Atta-ur-Rahman; Ed. Elsevier; Amsterdam: 1995: 687
• 3a Matsubara T, Takahashi K, Ishihara J, Hatakeyama S. Angew. Chem. Int. Ed. 2014; 53: 757
• 3b Ueoka R, Fujita T, Matsunaga S. J. Org. Chem. 2009; 74: 4396
• 3c Ebel H, Knör S, Steglich W. Tetrahedron 2003; 59: 123
• 3d Yamashita Y, Saito S, Ishitani H, Kobayashi S. J. Am. Chem. Soc. 2003; 125: 3793
• 3e Katzenellenbogen JA, Rai R, Dai W. Bioorg. Med. Chem. Lett. 1992; 2: 1399
• 3f Lambert JD, Rice JE, Hong J, Hou Z, Yang CS. Bioorg. Med. Chem. Lett. 2005; 15: 873

For selected papers dealing with iodolactonization, see:
• 4a Wzorek A, Gawdzik B, Gładkowski W, Urbaniak M, Barańska A, Malińska M, Woźniak K, Kempińska K, Wietrzyk J. J. Mol. Struct. 2013; 1047: 160
• 4b Časar Z. Synlett 2008; 2036
• 4c Oderinde MS, Hunter HN, Bremner SW, Organ MG. Eur. J. Org. Chem. 2012; 175

For selected recent papers on the use of δ-lactones as synthetic building blocks, see:
• 4d Časar Z, Steinbücher M, Košmrlj J. J. Org. Chem. 2010; 75: 6681
• 4e Fabris J, Časar Z, Smilović GI. Synthesis 2012; 44: 1700
• 4f Fabris J, Časar Z, Smilović GI, Črnugelj M. Synthesis 2014; 46: 2333

For selected papers on the synthesis of δ-lactones, see:
• 5a Brandau S, Landa A, Franzén J, Marigo M, Jørgensen KA. Angew. Chem. Int. Ed. 2006; 45: 4305

For those involving alcohol and ester lactonization, see:
• 5b Yadav JS, Reddy MK, Reddy PV. Tetrahedron Lett. 2007; 48: 1037
• 5c Chakraborty TK, Goswami RK. Tetrahedron Lett. 2004; 45: 7637
• 5d Singh RP, Singh VK. J. Org. Chem. 2004; 69: 3425
• 5e Shklyaruck D, Matiushenkov E. Tetrahedron: Asymmetry 2011; 22: 1448

For those involving β-hydroxy acylsilanes, see:
• 5f Murthy AS, Roisnel T, Chandrasekhar S, Grée R. Synlett 2013; 24: 2216

For the synthesis of prelactone B, see:
• 5g Dias LC, Steil LJ, Vasconcelos de A. V. Tetrahedron: Asymmetry 2004; 15: 147
• 5h Exner CJ, Laclef S, Poli F, Turks M, Vogel P. J. Org. Chem. 2011; 76: 840

For the synthesis of tanikolide, see:
• 5i Doran R, Duggan L, Singh S, Duffy CD, Guiry PJ. Eur. J. Org. Chem. 2011; 7097

For a Reformatsky-type reaction, see:
• 5j Navickas V, Rink C, Maier ME. Synlett 2011; 191

For NHC redox catalysis, see:
• 5k Davies AT, Pickett PM, Slawin AM. Z, Smith AD. ACS Catal. 2014; 4: 2696

For organocatalytic cascade reactions, see:
• 5l Ren Q, Sun S, Huang J, Li W, Wu M, Guo H, Wang J. Chem. Commun. 2014; 50: 6137

For a one-pot multistep method, see:
• 5m Saito A, Kumagai N, Shibasaki M. Tetrahedron Lett. 2014; 55: 3167

For Aldol product-based methods, see:
• 5n Peed J, Domínguez IP, Davies IR, Cheeseman M, Taylor JE, Kociok-Köhn G, Bull SD. Org. Lett. 2011; 13: 3592
• 5o Davies SG, Nicholson RL, Smith AD. Org. Biomol. Chem. 2004; 2: 3385
• 5p Ošlaj M, Cluzeau J, Orkić D, Kopitar G, Mrak P, Časar Z. PLoS One 2013; 8: e62250
• 5q Vajdič T, Ošlaj M, Kopitar G, Mrak P. Metab. Eng. 2014; 24: 160

For selected papers on the synthesis of γ-lactones: for metal-based synthesis, see:
• 6a Mladenova M, Gaudemar-Bardone F, Goasdoue N, Gaudemar M. Synthesis 1986; 937
• 6b Gaudemar-Bardone F, Gaudemar M, Mladenova M. Synthesis 1987; 1130
• 6c Babu SA, Yasuda M, Okabe Y, Shibata I, Baba A. Org. Lett. 2006; 8: 3029 and references cited therein
• 6d Habel A, Boland W. Org. Biomol. Chem. 2008; 6: 1601
• 6e Fillion E, Carret S, Mercier LG, Trépanier VÉ. Org. Lett. 2008; 10: 437
• 6f Rollin Y, Derien S, Duñach E, Gebehenne C, Perichon J. Tetrahedron 1993; 49: 7723
• 6g Pisani L, Superchi S, D’Elia A, Scafato P, Rosini C. Tetrahedron 2012; 68: 5779

For the dihydroxylation route, see:
• 6h Kapferer T, Brückner R. Eur. J. Org. Chem. 2006; 2119

For a C–H abstraction-based protocol, see:
• 6i Dohi T, Takenaga N, Goto A, Maruyama A, Kita Y. Org. Lett. 2007; 9: 3129

For TfOH-based construction of γ-lactones, see:
• 6j Elford TG, Arimura Y, Yu SH, Hall DG. J. Org. Chem. 2007; 72: 1276
• 6k Aslam NA, Babu SA. Tetrahedron 2014; 70: 6402

For a reduction/lactonization sequence-based method, see:
• 6l Steward KM, Gentry EC, Johnson JS. J. Am. Chem. Soc. 2012; 134: 7329

For selected papers and reviews on Barbier-type reactions, see:
• 7a Barbier P. C. R. Hebd. Seances Acad. Sci. 1899; 128: 110
• 7b Roush RW In Comprehensive Organic Synthesis . Vol. 2. Trost BM, Fleming I, Heathcock CH. Pergamon; Oxford: 1991: 1
• 7c Chemler SR, Roush WR In Modern Carbonyl Chemistry . Otera J. Wiley-VCH; Weinheim: 2000. Chap. 11, 403
• 7d Denmark SE, Almstead NG In Modern Carbonyl Chemistry . Otera J. Wiley-VCH; Weinheim: 2000. Chap. 10 299
• 7e Nair V, Ros S, Jayan CN, Pillai BS. Tetrahedron 2004; 60: 1959
• 7f Takao K.-i, Miyashita T, Akiyama N, Kurisu T, Tsunoda K, Tadano K.-i. Heterocycles 2012; 86: 147
• 7g Gao YZ, Wang X, Sun LD, Xie LG, Xu XH. Org. Biomol. Chem. 2012; 10: 3991
• 7h Lim JW, Kim KH, Park BR, Kim JN. Tetrahedron Lett. 2011; 52: 6545
• 7i Reddy C, Babu SA, Aslam NA. RSC Adv. 2014; 4: 40199 ; and references cited therein. See also Ref. 6 (a)
• 8 Crystallographic data for compounds 3b, 3c, 3t, and 4b have been deposited with the accession numbers CCDC 1048540, 1048541, 1048542, and 1048543, respectively, and can be obtained free of charge from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: [phone]; E-mail: [e-mail]; Web site: www.ccdc.cam.ac.uk/conts/retrieving.html.
• 9 γ-Lactones 3s–u and δ-Lactones 3a–r and 4a–h; General Procedure Zn powder (0.37 mmol) and allylbromide or 3-bromocyclohexene (0.5 mmol) were added to a solution of the appropriate malonate substrate 1 (0.25 mmol) in anhyd THF (1.5 mL) under N₂, and the mixture was stirred at 30–35 °C for the appropriate time (see Table 1 and Schemes 2–4). The reaction was then quenched by adding H₂O (2 mL), and the mixture was allowed to stand. The mixture was transferred to a separatory funnel and extracted with EtOAc (3 × 8 mL), and the organic layers were combined, dried (Na₂SO₄), filtered, and concentrated under vacuum. The resulting crude product was purified by column chromatography (silica gel, EtOAc–hexane). Ethyl (3S*,4S*,6S*)-6-Allyl-4-(4-chlorophenyl)-2-oxo-6-phenyltetrahydro-2H-pyran-3-carboxylate (3b) Prepared by the general procedure from 1b, and purified by column chromatography [silica gel, EtOAc–hexanes (13: 87)] as a colorless solid (major isomer); yield: 97 mg (98%; dr 75:25); mp 87–89 °C. IR (KBr): 1747, 1726, 1494 and 1155 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.41–7.28 (m, 5 H), 7.32 (d, J = 8.4 Hz, 2 H), 7.13 (d, J = 8.4 Hz, 2 H), 5.66–5.56 (m, 1 H), 5.16–5.11 (m, 2 H), 4.16–4.10 (m, 2 H), 3.81 (td, J₁  = 12.2 Hz, J₂  = 4.7 Hz, 1 H), 3.54 (d, J = 12.2 Hz, 1 H), 2.92 (dd, J₁  = 14.2 Hz, J₂  = 6.7 Hz, 1 H), 2.84 (dd, J₁  = 14.2 Hz, 1 H, J₂  = 7.6 Hz), 2.67 (dd, J₁  = 14.3 Hz, J₂  = 4.7 Hz, 1 H), 2.29 (dd, J₁  = 14.3 Hz, J₂  = 12.2 Hz, 1 H), 1.14 (t, J = 7.2 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 167.9, 166.9, 143.2, 138.8, 133.6, 131.4, 131.4, 129.2, 128.7, 128.4, 128.0, 124.6, 120.0, 86.1, 61.8, 54.2, 47.0, 39.3, 38.3, 14.0. HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₃H₂₃ClNaO₄: 421.1183; found: 421.1174.
• 10a This observation implies the stereoselection might occur at the Barbier reaction step through a plausible chelation effect involving the malonate moiety. This possibility is based on the observation that reaction in polar protic solvents such as EtOH gave no selectivity (Compare entries 1 and 3 in Table 1).
• 10b There was no significant change in the diastereoselectivity with respect to the two diastereomers obtained from reactions performed for different times. Furthermore, the diastereoselectivity of the crude reaction mixture did not differ significantly from that of the pure mixture of diastereomers obtained after isolation by column chromatography on silica gel.