mCPBA-mediated metal-free intramolecular aminohydroxylation and dioxygenation of unfunctionalized olefins

Abstract

mCPBA-mediated metal-free intramolecular aminohydroxylation and dioxygenation reactions of unfunctionalized olefins are reported. In the presence of 1.2 equiv. of m-chlorobenzoic peracid, different N-sulfonyl 4-penten-1-amine substrates could be cyclized via epoxide intermediates, producing the corresponding 2-hydroxymethylpyrrolidine products in up to 92% yields. The reaction could be carried out at gram-scale, and the hydroxyl group could be further converted to a variety of different functional groups via conventional functional group transformation reactions. When N-sulfonyl carboxylimides were subjected to the same reaction, O-cyclization products oxolanimines were obtained. The skeletons of these compounds were confirmed using X-ray diffraction experiments.

---

Introduction

1,2-Amino alcohols (β-amino alcohols) are widely present in natural products or biologically important compounds (Fig. 1),¹ and the Taxol side chain is one of the most famous examples of 1,2-amino alcohols. In addition, these compounds have also found widespread application in asymmetric synthesis as chiral auxiliaries and chiral ligands (Fig. 1).² To this end, continuous efforts have been devoted to the formation of 1,2-amino alcohols,³ and a variety of methods such as nucleophilic addition to carbonyl and imine compounds,⁴ ring-opening of epoxides/aziridines with suitable nucleophiles,⁵ C–H bond functionalizations⁶ or hydrogenation of α-amino ketones have been reported.⁷

Fig. 1 Examples of vicinal aminoalcohol-containing natural products, biologically active compounds, chiral auxiliaries and chiral ligands.

Among the variety of methods developed, aminohydroxylation of C=C double bonds is one of the most attractive strategies for the synthesis of 1,2-amino alcohols.⁸ Since the pioneering and elegant work reported by Sharpless,⁹ huge efforts have been made towards the transition metal-catalyzed aminohydroxylation of C=C double bonds, and a variety of efficient catalysts such as copper,¹⁰ palladium,¹¹ gold,¹² iron,¹³ rhodium,¹⁴ or platinum catalysts¹⁵ have been developed as a result.

In addition to these important achievements, metal free catalytic aminohydroxylation of unfunctionalized olefins has also been reported as one of the most efficient methods for the production of 1,2-amino alcohols. For example, hypervalent iodine reagents were able to promote aminohydroxylation of unfunctionalized olefins,¹⁶ and good to excellent enantioselectivities were realized when an appropriate chiral hypervalent iodine reagent was utilized.¹⁷ In another example, Moriyama et al. described oxone-promoted intramolecular oxidative cyclizations for the synthesis of substituted prolinol derivatives.¹⁸ Finally, Jørgensen and co-workers reported a formal asymmetric organocatalytic aminohydroxylation of enones via an aziridination-double S_N2 sequence.¹⁹ In this paper, we wish to report an mCPBA-mediated metal-free intramolecular aminohydroxylation approach to 1,2-amino alcohols as a continuation of our program on the functionalization of unactivated olefins.²⁰

Results and discussion

Very recently, we revealed that (diacetoxyiodo)benzene (PIDA) can be used to promote halocyclization of unfunctionalized olefins.²¹ In the presence of 1.1 equiv. of PIDA and suitable halogen sources, intramolecular haloamidation (iodo-, bromo-, chloro-, and fluoroamidation), haloetherification and halolactonization reactions could all be realized, giving the corresponding halocyclization products in good to excellent isolated yields. After establishing a general procedure for PIDA-promoted intramolecular halocyclization of unfunctionalized olefins, a catalytic version was also tested to reduce the amount of generally expensive (diacetoxyiodo)benzene (PIDA). Reactions in the presence of 10 mol% of PIDA and different oxidants were carried out to establish a catalytic protocol. To our surprise, when mCPBA was used as an oxidant, an aminohydroxylation product (2a) was obtained instead of an iodoamination product (3a) (Scheme 1).

Scheme 1 mCPBA-mediated intramolecular aminohydroxylation of 1a.

We reasoned that 2a should be generated through a tandem epoxidation and epoxide ring-opening sequence. Encouraged by this preliminary result, the reaction parameters such as oxidants or solvents were examined to get the optimal reaction conditions, and the results are summarized in Table 1. The reaction could be carried out at room temperature in the presence of 1.2 equiv. of mCPBA, and the substrate 1a could be converted to the prolinol product 2a in 86% isolated yield. mCPBA was essential for the successful transformation and no product was obtained in the absence of mCPBA (entries 1 and 2, respectively). Replacing mCPBA with other oxidants led to a drop of isolated yield (entries 3 to 6). The effect of the solvents on the course of the reaction was also noteworthy, and CH₂Cl₂ was the most suitable solvent for the reaction. Reactions carried out in MeOH, THF or CH₃CN gave remarkably lower yields (entries 7 to 9).

Table 1 Optimization of the reaction conditions^a

Entry	Reaction conditions	Isolated yield (%)
a All the reactions were run at 0.5 mmol scale in 20 mL of solvent. Reaction temperature: room temperature (25 °C). NR = no reaction.
1	Standard conditions	86
2	No mCPBA	NR
3	Oxone instead of mCPBA	NR
4	H2O2 instead of mCPBA	8
5	TBHP instead of mCPBA	NR
6	AcOOH instead of mCPBA	11
7	MeOH instead of CH2Cl2	NR
8	THF instead of CH2Cl2	15
9	CH3CN instead of CH2Cl2	32

---

With the optimized conditions in hand, different substrates were tested to study the scope of the reaction, and the results are summarized in Table 2.

Table 2 Substrate scope of mCPBA-mediated aminohydroxylation^a

Entry	Substrate	Product	Time (h)	Isolated yield (%)
a Reaction conditions: the reactions were carried out with 0.5 mmol of substrate, 0.6 mmol of mCPBA in 20 mL of DCM.
1	R = Tol (1a)	2a	18 h	86
2	R = 2-NO2Ph (1b)	2b	48 h, 40 °C	63
3	R = Me (1c)	2c	15 h	92
4	R = Tol (1d)	2d	15 h	88
5	R = 4-NO2Ph (1e)	2e	48 h, 40 °C	67
6	R = Ph (1f)	2f	20 h	80
7	R = H (1g)	2g	36 h	83
8	R = OMe (1h)	2h	24 h	88
9	R = Me (1i)	2i	24 h	78
10	R = Cl (1j)	2j	48 h, 40 °C	67
11	R = F (1k)	2k	24 h, 50 °C	70
12	R = CN (1l)	2l	40 h, 50 °C	62
13	R = 4-Tol (1m)	2m	20 h	75
14	R = Ph (1n)	2n	15 h	80
15	R = 2-Tol (1o)	2o	18 h	79
16			22 h	65
17	n = 1 (1q)	n = 1 2q	15 h	83
18	n = 2 (1r)	n = 2 2r	15 h	86
19			28 h	75 (dr > 20 : 1)
20			36 h	73
21			24 h	86 (dr = 60 : 40)
22			30 h	80 (dr = 2 : 1 : 1)

---

As shown in Table 2, the intramolecular aminohydroxylation of N-alkenylsulfonamides proceeded readily, giving the corresponding prolinol derivatives in good isolated yields. N-Substituents had some impacts on the reaction outcomes (entries 1–6). Long reaction times and high temperatures were essential to achieve satisfactory yields for substrates bearing electron deficient N-substituents (entries 2 and 5). This was possibly due to the low nucleophilicity of the sulfonamide caused by the strong electron withdrawing nitro group at the para-position of the benzene ring (entry 2 and entry 5). N-Tosyl-o-allyl aniline substrates could also be cyclized, giving the corresponding indoline derivatives in moderate isolated yields (entries 7–12). The drop in isolated yields may be due to the decreased reactivity of the sulfonamide aniline nitrogen atoms. Methoxy, methyl, halogen and cyano groups on the benzene ring could all be tolerated during the reactions. Again, the electronic effect of the aromatic rings influenced the course of the reaction. The Thorpe–Ingold effect showed less impact on the reaction, and the substrates without gem-disubstituents also gave acceptable isolated yields (entries 13–15). Different substituents on the main chain of the substrates did not significantly influence the reaction outcomes (entries 16–18). Substituents on C=C double bonds showed less impact on the reaction. Di- and trisubstituted terminal alkenes were efficiently converted into secondary and tertiary alcohols in good yield, respectively (entries 19–20). When the E-substrate 1s was subjected to the reaction, an erythro-product was obtained and the structure was confirmed using X-ray diffraction experiments (Fig. 2). The chiral substrate 1u gave a good isolated yield, but low diastereoselectivity (entry 21). Furthermore, the current protocol was also applicable to the synthesis of 2,7-diazaspirobicyclic compound 2v (entry 22).

Fig. 2 ORTEP drawing of 2s‡ with the thermal ellipsoids at 30% probability. Hydrogen atoms were omitted for clarity.

5-Hexen-1-amine substrate 1w failed to give the desired product possibly due to the unfavorable entropy feature of the cyclization reaction.²² In this case, the epoxide 2w′ was obtained in 89% yield (Scheme 2, eqn (1)), and 90% of the epoxide could be recovered after being heated in DCE at 90 °C for 36 h (Scheme 2, eqn (2)). However, when the epoxide 2w′ was allowed to react in the presence of base (2 equiv. of NaOH), the desired piperidinylmethanol 2w could also be obtained in good isolated yield (Scheme 2, eqn (3)).

Scheme 2 Reaction of the 5-hexen-1-amine substrate.

To evaluate the scalability of the current protocol, the reaction of 1a on gram scale was carried out and the product 2a could be isolated in 84% yield (Scheme 3). Subsequently, the hydroxyl group in 2a could be converted to a variety of functional groups using known procedures such as azidation,²³ bromination,²⁴ acetylation,^16b carboxylation ¹⁸ and Swern oxidation.²⁵ The current method therefore opened up a new route to a variety ofbiologically interesting structures.²⁶

Scheme 3 Gram-scale aminohydroxylation and transformation of the hydroxyl group to different functional groups. Conditions: (a) 1a (10 mmol), mCPBA (12 mmol), DCM, r.t., 24 h. (b) 2a, DPPA, DBU, toluene/DMF (9 : 1), 50 °C, 48 h. (c) 2a, PBr₃, Et₂O, r.t., overnight. (d) 2a, Ac₂O, 4-DMAP, Et₃N, 0 °C, 30 min. (e) 2a, DIAB, TEMPO, CH₃CN/H₂O (1 : 1), r.t., 12 h. (f) 2a, (COCl)₂, DMSO, Et₃N, DCM, −78 °C, 30 min.

After the successful aminohydroxylation of sulfonamide substrates, the application scope of mCPBA-mediated aminohydroxylation was extended. When N-tosyl amide 8a was subjected to reaction under the standard conditions, an O-cyclization product oxolanimine 9a was obtained as the major product (Scheme 4), and the structure of oxolanimine 9a was unambiguously confirmed using NMR spectroscopy and X-ray diffraction studies (Fig. 3). A trace amount of the N-cyclization product, lactam 9a′ was also detected.

Scheme 4 Oxyhydroxylation of 8a.

Fig. 3 ORTEP drawing of 9a§ with the thermal ellipsoids at 30% probability. Hydrogen atoms were omitted for clarity.

Encouraged by this result, a variety of substrates were then tested to study the scope of the reaction, and the results are summarized in Scheme 5. In general, the cyclization products were obtained with excellent regioselectivity and in good yields. Different substituents on the main chain did not significantly influence the reaction outcomes.

Scheme 5 mCPBA-mediated dioxygenation of the N-tosyl amide substrate.

Conclusions

In summary, mCPBA was effective for the functionalization of unactivated C=C double bonds. Intramolecular aminohydroxylation and dioxygenation reactions could all be realized in the presence of 1.2 equiv. of mCPBA. This metal-free method will complement the existing aminohydroxylation methods, especially osmium-based approaches. The reaction could be carried out at gram-scale, and the hydroxyl group could be easily converted to other functional groups via conventional methods. We envisage that the present protocol will attract the attention of synthetic chemists in the fields of medicinal and agrochemical research due to the good isolated yields, mild conditions and easy-to-operate features of thereactions.

Experimental section

General methods

Reagents were used as received without further purification unless otherwise specified. Solvents were dried and distilled prior to use. Reactions were monitored with thin layer chromatography using silica gel GF₂₅₄ plates. Organic solutions were concentrated in vacuo using a rotary evaporator. Flash column chromatography was performed using silica gel (200–300 meshes). The petroleum ether used had a boiling point range of 60–90 °C. Melting points were measured on digital melting point apparatus without correction of the thermometer. Nuclear magnetic resonance spectra were recorded at ambient temperature (unless otherwise stated) at 400 MHz (100 MHz for ¹³C) in CDCl₃. Chemical shifts are reported in ppm (δ) using TMS as internal standard, and spin–spin coupling constants (J) are given in Hz. High resolution mass spectrometry (HRMS) analyses were carried out on an IonSpec 7.0T FTICR HR-ESI-MS.

General procedure for intramolecular aminohydroxylation and dioxygenation

In a 100 mL round-bottomed flask alkenylamine (0.5 mmol) and mCPBA (0.6 mmol) in dry CH₂Cl₂ (20 mL) were added. The mixture was stirred at room temperature for a given time. CH₂Cl₂ (10 mL) was then added and the mixture was washed with aqueous Na₂S₂O₃ and aqueous NaHCO₃, dried over MgSO₄, and concentrated to give a crude residue which was purified using flash column chromatography to give the corresponding products.

Acknowledgements

We acknowledge the financial support from the National Natural Science Foundation of China (NSFC 20972072, NSFC 21272121). G.-Q. Liu acknowledges the support from The Ph. D. Student Innovative Research Program of Nankai University (68140001).

Notes and references

1. (a) D. O’Hagan, Nat. Prod. Rep., 2000, 17, 435–446; (b) J. R. Lewis, Nat. Prod. Rep., 2001, 18, 95–128.
2. (a) A. I. Meyers, D. R. Williams and M. Druelinger, J. Am. Chem. Soc., 1976, 98, 3032–3033; (b) A. Hirao, S. Itsuno, S. Nakahama and N. Yamazaki, J. Chem. Soc., Chem. Commun., 1981, 315–317; (c) E. J. Corey, R. K. Bakshi and S. Shibata, J. Am. Chem. Soc., 1987, 109, 5551–5553; (d) D. J. Ager, I. Prakash and D. R. Schaad, Chem. Rev., 1996, 96, 835–876; (e) I. Schiffers, T. Rantanen, F. Schmidt, W. Bergmans, L. Zani and C. Bolm, J. Org. Chem., 2006, 71, 2320–2331.
3. (a) S. C. Bergmeier, Tetrahedron, 2000, 56, 2561–2576; (b) O. K. Karjalainen and A. M. P. Koskinen, Org. Biomol. Chem., 2012, 10, 4311–4326.
4. (a) F. A. Luzzio, Tetrahedron, 2001, 57, 915–945; (b) S. Kobayashi, Y. Mori, J. S. Fossey and M. M. Salter, Chem. Rev., 2011, 111, 2626–2704.
5. (a) D. M. Hodgson, A. R. Gibbs and G. P. Lee, Tetrahedron, 1996, 52, 14361–14384; (b) J. B. Sweeney, Chem. Soc. Rev., 2002, 31, 247–258; (c) X. E. Hu, Tetrahedron, 2004, 60, 2701–2743.
6. (a) C. G. Espino and J. Du Bois, Angew. Chem., Int. Ed., 2001, 40, 598–600; (b) J.-L. Liang, S.-X. Yuan, J.-S. Huang, W.-Y. Yu and C.-M. Che, Angew. Chem., Int. Ed., 2002, 41, 3465–3468; (c) H. Lebel, K. Huard and S. Lectard, J. Am. Chem. Soc., 2005, 127, 14198–14199; (d) K. J. Fraunhoffer and M. C. White, J. Am. Chem. Soc., 2007, 129, 7274–7276; (e) T. Kang, H. Kim, J. G. Kim and S. Chang, Chem. Commun., 2014, 50, 12073–12075.
7. (a) H. Takahashi, S. Sakuraba, H. Takeda and K. Achiwa, J. Am. Chem. Soc., 1990, 112, 5876–5878; (b) T. Ohkuma, D. Ishii, H. Takeno and R. Noyori, J. Am. Chem. Soc., 2000, 122, 6510–6511; (c) A. Lei, S. Wu, M. He and X. Zhang, J. Am. Chem. Soc., 2004, 126, 1626–1627; (d) S. Liu, J.-H. Xie, L.-X. Wang and Q.-L. Zhou, Angew. Chem., Int. Ed., 2007, 46, 7506–7508; (e) P. He, H. Zheng, X. Liu, X. Lian, L. Lin and X. Feng, Chem.–Eur. J., 2014, 20, 13482–13486.
8. (a) D. Nilov and O. Reiser, Adv. Synth. Catal., 2002, 344, 1169–1173; (b) J. A. Bodkin and M. D. McLeod, J. Chem. Soc., Perkin Trans. 1, 2002, 2733–2746; (c) K. Muniz, Chem. Soc. Rev., 2004, 33, 166–174; (d) T. J. Donohoe, C. K. A. Callens, A. Flores, A. R. Lacy and A. H. Rathi, Chem.–Eur. J., 2011, 17, 58–76.
9. (a) K. B. Sharpless, A. O. Chong and K. Oshima, J. Org. Chem., 1976, 41, 177–179; (b) G. Li, H.-T. Chang and K. B. Sharpless, Angew. Chem., Int. Ed., 1996, 35, 451–454.
10. (a) M. Noack and R. Gottlich, Chem. Commun., 2002, 536–537; (b) D. J. Michaelis, C. J. Shaffer and T. P. Yoon, J. Am. Chem. Soc., 2007, 129, 1866–1867; (c) D. J. Michaelis, M. A. Ischay and T. P. Yoon, J. Am. Chem. Soc., 2008, 130, 6610–6615; (d) P. H. Fuller, J.-W. Kim and S. R. Chemler, J. Am. Chem. Soc., 2008, 130, 17638–17639; (e) T. Benkovics, J. Du, I. A. Guzei and T. P. Yoon, J. Org. Chem., 2009, 74, 5545–5552; (f) M. C. Paderes and S. R. Chemler, Org. Lett., 2009, 11, 1915–1918; (g) D. J. Michaelis, K. S. Williamson and T. P. Yoon, Tetrahedron, 2009, 65, 5118–5124; (h) T. Benkovics, I. A. Guzei and T. P. Yoon, Angew. Chem., Int. Ed., 2010, 49, 9153–9157; (i) S. M. DePorter, A. C. Jacobsen, K. M. Partridge, K. S. Williamson and T. P. Yoon, Tetrahedron Lett., 2010, 51, 5223–5225; (j) D. E. Mancheno, A. R. Thornton, A. H. Stoll, A. Kong and S. B. Blakey, Org. Lett., 2010, 12, 4110–4113; (k) F. C. Sequeira and S. R. Chemler, Org. Lett., 2012, 14, 4482–4485; (l) M. C. Paderes, L. Belding, B. Fanovic, T. Dudding, J. B. Keister and S. R. Chemler, Chem.–Eur. J., 2012, 18, 1711–1726; (m) M. C. Paderes, J. B. Keister and S. R. Chemler, J. Org. Chem., 2012, 78, 506–515.
11. (a) E. J. Alexanian, C. Lee and E. J. Sorensen, J. Am. Chem. Soc., 2005, 127, 7690–7691; (b) P. Szolcsanyi and T. Gracza, Chem. Commun., 2005, 3948–3950; (c) G. Liu and S. S. Stahl, J. Am. Chem. Soc., 2006, 128, 7179–7181; (d) L. V. Desai and M. S. Sanford, Angew. Chem., Int. Ed., 2007, 46, 5737–5740; (e) D. V. Liskin, P. A. Sibbald, C. F. Rosewall and F. E. Michael, J. Org. Chem., 2010, 75, 6294–6296; (f) H. Zhu, P. Chen and G. Liu, J. Am. Chem. Soc., 2014, 136, 1766–1769.
12. T. de Haro and C. Nevado, Angew. Chem., Int. Ed., 2011, 50, 906–910.
13. (a) K. S. Williamson and T. P. Yoon, J. Am. Chem. Soc., 2010, 132, 4570–4571; (b) K. S. Williamson and T. P. Yoon, J. Am. Chem. Soc., 2012, 134, 12370–12373; (c) G.-S. Liu, Y.-Q. Zhang, Y.-A. Yuan and H. Xu, J. Am. Chem. Soc., 2013, 135, 3343–3346; (d) D.-F. Lu, C.-L. Zhu, Z.-X. Jia and H. Xu, J. Am. Chem. Soc., 2014, 136, 13186–13189.
14. (a) E. Levites-Agababa, E. Menhaji, L. N. Perlson and C. M. Rojas, Org. Lett., 2002, 4, 863–865; (b) A. Padwa and T. Stengel, Org. Lett., 2002, 4, 2137–2139; (c) S. Beaumont, V. Pons, P. Retailleau, R. H. Dodd and P. Dauban, Angew. Chem., Int. Ed., 2010, 49, 1634–1637; (d) W. P. Unsworth, N. Clark, T. O. Ronson, K. Stevens, A. L. Thompson, S. G. Lamont and J. Robertson, Chem. Commun., 2014, 50, 11393–11396.
15. K. Muniz, A. Iglesias and Y. Fang, Chem. Commun., 2009, 5591–5593.
16. (a) S. Serna, I. Tellitu, E. Domínguez, I. Moreno and R. SanMartin, Tetrahedron, 2004, 60, 6533–6539; (b) A. Correa, I. Tellitu, E. Domínguez and R. SanMartin, J. Org. Chem., 2006, 71, 8316–8319; (c) B. M. Cochran and F. E. Michael, Org. Lett., 2008, 10, 5039–5042; (d) D. J. Wardrop, E. G. Bowen, R. E. Forslund, A. D. Sussman and S. L. Weerasekera, J. Am. Chem. Soc., 2009, 132, 1188–1189; (e) H. Li and R. A. Widenhoefer, Tetrahedron, 2010, 66, 4827–4831; (f) H. J. Kim, S. H. Cho and S. Chang, Org. Lett., 2012, 14, 1424–1427.
17. (a) C. Röben, J. A. Souto, Y. González, A. Lishchynskyi and K. Muñiz, Angew. Chem., Int. Ed., 2011, 50, 9478–9482; (b) U. Farid and T. Wirth, Angew. Chem., Int. Ed., 2012, 51, 3462–3465.
18. K. Moriyama, Y. Izumisawa and H. Togo, J. Org. Chem., 2012, 77, 9846–9851.
19. D. C. Cruz, P. A. Sanchez-Murcia and K. A. Jorgensen, Chem. Commun., 2012, 48, 6112–6114.
20. (a) G.-Q. Liu, W. Li, Y.-M. Wang, Z.-Y. Ding and Y.-M. Li, Tetrahedron Lett., 2012, 53, 4393–4396; (b) G.-Q. Liu, Z.-Y. Ding, L. Zhang, T.-T. Li, L. Li, L. Duan and Y.-M. Li, Adv. Synth. Catal., 2013, 356, 2303–2310; (c) R.-L. Li, G.-Q. Liu, W. Li, Y.-M. Wang, L. Li, L. Duan and Y.-M. Li, Tetrahedron, 2013, 69, 5867–5873.
21. G.-Q. Liu and Y.-M. Li, J. Org. Chem., 2014, 79, 10094–10109.
22. (a) G. Illuminati and L. Mandolini, Acc. Chem. Res., 1981, 14, 95–102; (b) A. J. Kirby, in Advances in Physical Organic Chemistry, ed. V. Gold and D. Bethell, Academic Press, 1981, pp. 183–278; (c) T. G. Denisova and E. T. Denisov, Russ. Chem. Bull., 2002, 51, 949–960.
23. A. S. Thompson, G. R. Humphrey, A. M. DeMarco, D. J. Mathre and E. J. J. Grabowski, J. Org. Chem., 1993, 58, 5886–5888.
24. G. C. Harrison and H. Diehl, Org. Synth., 1943, 23, 32.
25. K. Omura and D. Swern, Tetrahedron, 1978, 34, 1651–1660.
26. (a) P. J. Lovell, S. M. Bromidge, S. Dabbs, D. M. Duckworth, I. T. Forbes, A. J. Jennings, F. D. King, D. N. Middlemiss, S. K. Rahman, D. V. Saunders, L. L. Collin, J. J. Hagan, G. J. Riley and D. R. Thomas, J. Med. Chem., 2000, 43, 342–345; (b) J. Andriès, L. Lemoine, A. Mouchel-Blaisot, S. Tang, M. Verdurand, D. Le Bars, L. Zimmer and T. Billard, Bioorg. Med. Chem. Lett., 2010, 20, 3730–3733.

---

Footnotes

† Electronic supplementary information (ESI) available: General information of the reaction, characterization of products, and X-ray diffraction results for 2s and 9a. CCDC 1400823 and 1400825. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5ra09024e

‡ Crystal data for 2s: C₂₅H₂₇NO₃S, M = 421.54, monoclinic, a = 14.198(3) Å, b = 6.0639(12) Å, c = 25.178(5) Å, α = 90.00°, β = 100.14(3)°, γ = 90.00°, V = 2133.9(7) ų, T = 113(2) K, space group P2(1)/c, Z = 4, μ(MoKα) = 0.179 mm⁻¹, 15 871 reflections measured, 5063 independent reflections (R_int = 0.0444). The final R₁ values were 0.0443 (I > 2σ(I)). The final wR(F²) values were 0.1187 (I > 2σ(I)). The final R₁ values were 0.0551 (all data). The final wR(F²) values were 0.1284 (all data). The goodness of fit on F² was 1.011. The CIF for 2s has been deposited in the CCDC with deposition number CCDC 1400823.

§ Crystal data for 9a: C₁₃H₁₇NO₄S, M = 283.34, orthorhombic, a = 8.6906(17) Å, b = 11.953(2) Å, c = 13.546(3) Å, α = 90.00°, β = 90.00°, γ = 90.00°, V = 1407.1(5) ų, T = 113(2) K, space group P2(1)2(1)2(1), Z = 4, μ(MoKα) = 0.239 mm⁻¹, 16 639 reflections measured, 3374 independent reflections (R_int = 0.0564). The final R₁ values were 0.0592 (I > 2σ(I)). The final wR(F²) values were 0.1544 (I > 2σ(I)). The final R₁ values were 0.0641 (all data). The final wR(F²) values were 0.1598 (all data). The goodness of fit on F² was 1.038. Flack parameter = −0.01(12). The CIF for 9a has been deposited in the CCDC with deposition number CCDC 1400825.

---