Download PDF
Synthesis 2010(4): 678-688  
DOI: 10.1055/s-0029-1218581
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of N-(Benzyloxyethyl)- and N-(Alkoxycarbonylmethyl)nitrones

Alba Diez-Martinez, Zeynep Gultekin, Ignacio Delso, Tomas Tejero, Pedro Merino*
Laboratorio de Sintesis Asimetrica, Departamento de Quimica Organica, Instituto de Ciencia de Materiales de Aragón, Universidad de Zaragoza - CSIC, 50009 Zaragoza, Aragon, Spain
Fax: +34(976)762075; e-Mail: pmerino@unizar.es;

Further Information

Publication History

Received 5 October 2009
Publication Date:
27 November 2009 (online)

 PDF Download Permissions and Reprints All articles of this category

Abstract

Highly efficient procedures for the preparation of nitrones bearing an oxygenated functionality at the β-position of the nitrone nitrogen, via either condensation of hydroxylamines with aldehydes or oxidation of the precursor imine, are described. The reactions proceeded smoothly at ambient temperature and the desired products were obtained in high to excellent yields. A total of 45 nitrones and 16 single-crystal analyses have been obtained.

Key words

nitrones - hydroxylamines - oxidation - aldehydes - condensation

Nitrones are used as versatile components in nucleophilic addition reactions with organometallic reagents [¹] and in 1,3-dipolar cycloadditions [²] and they have potential for therapeutic applications as anti-inflammatory agents [³] and antioxidants [4] with application in age-related diseases, [5] cerebral ischemia, [6] and acute or progressive neurodegenerative disorders. [7] Typically, nitrones can be prepared by either condensation of a carbonyl compound and a hydroxylamine or by oxidation of the corresponding amine or hydroxylamine (Scheme  [¹] ). [8]

Scheme 1

In general, the condensation route is more adequate for acyclic aldonitrones [9] and ketonitrones [¹0] whereas the oxidation route is preferred for preparing cyclic nitrones. [¹¹] In the case of acyclic nitrones, the nitrone nitrogen substituent (PG) usually consists of a removable group in order to facilitate further transformations towards the free amine after key nucleophilic addition (NA) or dipolar cycloaddition (DC) reactions (Scheme  [²] ). [¹²] However, the presence of suitable chains with additional functionalization at the nitrone nitrogen could provide access to more complex structures without the necessity of eliminating the residue linked to the nitrogen atom. In this context, and in order to continue with our studies directed to the synthesis of nitrogen-containing saturated systems using nitrones as key starting materials, [¹a] [b] [¹²] we were interested in substrates possessing an oxygenated functionality in the β-position to the nitrogen atom. [¹³] In particular, our interest was focused on alkyl- and aryl-substituted aldonitrones 1 and 2 bearing a methoxycarbonyl group and a benzyloxy group, respectively (Figure  [¹] ). In the case of compounds 2, we also considered the presence of a chiral center adjacent to the nitrogen atom.

Scheme 2

Figure 1

In this paper we describe the preparation of compounds 1 and 2 and discuss the synthetic approach in each case.

The synthesis of nitrones 1 through the condensation method required the availability of N-hydroxyglycinates 7 in multigram scale. Although the synthesis of (benzyl­oxycarbonyl)methylhydroxylamine oxalate, from benzyl glycinate 3a in three steps has been reported (Scheme  [³] ), [¹4] careful evaluation of this method revealed several issues that rendered it far from ideal for economical, safe, and efficient multigram synthesis of N-hydroxy­glycinates 7.

Scheme 3

The main detrimental attribute observed was the inefficiency found in the oxidation of intermediate N-(cyano­methyl)amine 4 (complex mixtures of nitrones 5 and 6 could be identified) when applied to glycinates 3. In these cases only milligrams (<10%) of the final product, isolated as the corresponding oxalate as described, [¹4] could be obtained. In addition, further attempts to condense the salt with aldehydes failed under several reaction conditions. To circumvent the above complications resulting from the oxidation of 4 and added drawbacks derived from transoximation of 6, we considered an alternative oxidation protocol to obtain the target nitrones 1. This approach, however, also presented a difficulty concerning the presence of the ester functionality, which could lead to mixtures of nitrones as in the case of the oxidation of 4. The best way to avoid formation of mixtures of nitrones is to prepare them directly from the corresponding imine, in order to point the regioselectivity of the oxidation toward the desired side. The oxidation of imines to nitrones has been an unresolved issue for years, [8] but very recently, Goti and co-workers reported [¹5] an efficient and atom-economic protocol for the direct oxidation of imines to nitrones based on the methyltrioxorhenium/urea-hydrogen peroxide complex (MeReO3/UHP) system. [¹6] Hence, we decided to apply Goti’s methodology to the preparation of 1. A series of aromatic aldimines were prepared by treatment of the corresponding aldehyde 9 with the hydrochloride salt of the glycinate 8, previously neutralized in situ with triethylamine. Imines 10 were obtained in good yields and used in the next step without purification. Oxidation of 10 was performed by treatment with a catalytic amount (2 mol%) of methyltrioxorhenium in the presence of 3.0 equivalents of urea-hydrogen peroxide complex in methanol as a solvent (Scheme  [4] , Table  [¹] ).

Scheme 4

Table 1 C-Aryl-N-(alkoxycarbonylmethyl)nitrones 1a-o
Entry Nitrone R¹ R² Time (h) Yield (%)
 1 1a Me Ph 12 88
 2 1b Me 4-MeOC6H4 24 90
 3 1c Me 4-BrC6H4 48 80
 4 1d Me 4-ClC6H4 24 79
 5 1e Me 4-MeC6H4 48 85
 6 1f Me 4-PhC6H4 48 69
 7 1g Me 4-O2NC6H4 48 80
 8 1h Me 4-NCC6H4 48 83
 9 1i Me 1-naphthyl 48 65
10 1j Bn Ph 12 89
11 1k Bn 4-MeOC6H4 24 81
15 1l Et Ph 16 92

In this way, the synthesis of nitrones 1 was straightforward and completely regioselective. After completion of the reaction (TLC), nitrones 1 were isolated and purified by column chromatography to provide stable, easy-to-handle solids of high purity. The above synthetic efforts allowed the successful synthesis of multigram quantities (30-mmol scale) of 1a-l in one pot from the glycinate salt.

All the nitrones 1a-l were obtained as single isomers and the expected Z-configuration was confirmed by ¹H NMR NOEDIF experiments, which showed an enhancement of the NCH 2 signal upon irradiation of the azomethine hydrogen and vice versa. The previously described ASIS effect [¹7] for nitrones also served to confirm the configuration of nitrones 1a-l and in the cases of nitrones 1a, 1c, 1d, 1f, and 1h-k single-crystal X-ray structures [¹8] provided additional proofs of the Z-configuration.

The methodology outlined in Scheme  [4] and Table  [¹] is limited to C-arylnitrones as they are formed from the corresponding arylimines, which are rapidly obtained in good yields. On the other hand, since alkylimines are more difficult to obtain and they are not so stable, the synthesis of C-alkylnitrones of type 1 remained more challenging. After having no success with alkylimines, we decided to explore the condensation method. We were able to prepare hydroxylamines 7a and 7b by a transoximation reaction from C-arylnitrones 1a and 1j, respectively (Scheme  [5] ). Several conditions have been reported for the transoximation of nitrones. [¹9] They involved different reaction times, solvents, and temperatures depending on the substrate to which were applied. These procedures suffered from shortcomings such as irreproducibility and difficult isolation and purification procedures. Other experimental procedures, [¹³d] [e] although valid on a millimole scale, showed only partial conversion when scaled up by 30-fold. Optimization of the reaction conditions by adjusting pH = 6 and maintaining the reaction mixture at reflux in methanol for one hour resulted in high conversions and chemical yields. Very recently, Dujardin and co-workers reported [²0] a large-scale preparation of N-benzylhydroxylamine. A key step in their method consisted of the hydrolysis of a C-phenylnitrone in such a way that benzaldehyde is eliminated as it is produced. Application of this technology to nitrones 1a,j gave the corresponding hydroxylamine hydrochlorides 7a˙HCl and 7b˙HCl in acceptable yields. Although the methodology is limited to C-phenylnitrones, it provides an excellent way to obtain hydrochlorides that can be stored for a long time. It is more expeditious in the transoxamination to use the hydroxylamine immediately, thus avoiding intermediate steps needed to liberate the hydroxylamine in its base-free form.

Condensation of 7a,b with isobutyraldehyde or pivaldehyde in dichloromethane in the presence of magnesium sulfate as a desiccating agent afforded nitrones 1m-o in excellent yield, thus demonstrating accessibility to C-alkyl-N-(alkoxycarbonylmethyl)nitrones.

Scheme 5

The synthesis of nitrones 2a-k bearing an aryl group at the nitrone carbon atom were achieved from the precursor imines 13 through the methyltrioxorhenium-based approach (Scheme  [6] , Table  [²] ). Intermediates 13 were prepared in situ from commercially available amino alcohols 11a-c as illustrated in Scheme  [6] .

Scheme 6

Table 2 C-Aryl-N-[2-(benzyloxy)ethyl]nitrones 2a-k a
Entry Nitrone R¹ R² Time (h) Yield (%)
 1 2a H Ph 16 90
 2 2b H 4-O2NC6H4 16 92
 3 2c H 4-MeOC6H4 16 91
 4 2d i-Pr Ph 16 85
 5 2e i-Pr 4-O2NC6H4 16 88
 6 2f i-Pr 4-MeOC6H4 16 91
 8 2g i-Pr 2-furyl 14 87
 9 2h Ph Ph 24 86
10 2i Ph 4-O2NC6H4 24 92
11 2j Ph 4-MeOC6H4 24 90
13 2k Ph 2-furyl 20 85
a R¹ = i-Pr and Ph series refer to S- and R-configurations, respectively.

With a practical preparation of hydroxylamines through a transoximation process, as discussed before we also decided to investigate the synthesis of homochiral nitrones 2 bearing a C-alkyl chain through the condensation method. The best results for transoximation reactions of C-aryl­nitrones 2 were achieved with anisaldehyde-derived nitrones­ 2f and 2j, which were used the preparation of the required hydroxylamines 14. Condensation of 14 with aliphatic­ aldehydes afforded C-alkylnitrones 2l-z (Scheme  [7] , Table  [³] ) in very good yields. All the nitrones 2 were shown to have the Z-configuration by conventional NMR techniques. Such a configuration was further confirmed through X-ray analyses for nitrones 2a, 2b, 2d, 2f, 2g, 2j, 2n, and 2q.

Table 3 C-Alkyl-N-[2-(benzyloxy)ethyl]nitrones 2l-z a
Entry Nitrone R¹ R² Yield (%)
 1 2l i-Pr Mr 81
 2 2m i-Pr i-Pr 85
 3 2n i-Pr n-Pr 95
 4 2o i-Pr i-Pr 94
 5 2p i-Pr t-Bu 88
 6 2q i-Pr n-Bu 82
 7 2r i-Pr Bn 86
 8 2s i-Pr (CH2)2Ph 89
 9 2t i-Pr CH2OBn 78
10 2u i-Pr CH2NHBoc 75
11 2v Ph Me 86
12 2w Ph i-Pr 95
13 2x Ph t-Bu 90
14 2y Ph CH2OBn 87
15 2z Ph CH2NHBoc 82
a R¹ = i-Pr and Ph series refer to S- and R-configurations, respectively.

Scheme 7

In summary, efficient multigram syntheses of a total of 45 nitrones bearing an oxygenated functionality at the β-position of the nitrone nitrogen atom is described. Their Z-configuration has been confirmed by NMR spectroscopy and 16 single-crystal X-ray analyses. While the synthesis of C-arylnitrones is straightforward by oxidation of the precursor imine, condensation between aldehydes and hydroxylamines is preferred the preparation of C-alkyl­nitrones. In these cases it is necessary to prepare the required hydroxylamine through a transoximation reaction, the best results being obtained from anisaldehyde-derived nitrones.

The reaction flasks and other glass equipment were heated in an oven at 130 ˚C overnight and assembled in a stream of argon. All reactions were monitored by TLC on silica gel 60 F254; the position of the spots was detected with 254 nm UV light or by spraying with 5% ethanolic phosphomolybdic acid. Column chromatography was carried out in a Buchi 800 MPLC system using silica gel 60 µm. Melting points were uncorrected. ¹H and ¹³C NMR spectra were recorded on Bruker Avance 400 instrument in the stated solvent. Chemical shifts are reported relative to CHCl3 (δH = 7.26, δC = 77.0) in CDCl3. Optical rotations were taken on a Jasco P-1020 DIP-370 polarimeter. Elemental analyses were performed on a Perkin­-Elmer 240B microanalyzer or with a Perkin-Elmer 2400 instrument.

Synthesis of Nitrones 1a-1; General Procedure

A suspension of the corresponding glycinate hydrochloride 8 (30 mmol) in CH2Cl2 (50 mL) was treated with Et3N (30 mmol); the resulting mixture was stirred vigorously at r.t. for 2 h under an argon atmosphere. The aldehyde 9 (30 mmol) was added and stirring was maintained at r.t. for an additional 24 h. The mixture was filtered through a pad of Celite and the filtrate was evaporated under reduced pressure to give crude imine 10, which was taken up in MeOH (40 mL) and treated sequentially with MgSO4 (3.61 g, 30 mmol), MeReO3 (0.15 g, 0.56 mmol), and UHP (8.50 g, 90 mmol). The resulting mixture was stirred for the stated time (see Table  [¹] ) at r.t., filtered, and evaporated under reduced pressure. The crude product was purified by column chromatography (hexane-EtOAc, gradient 7:3 to 1:1).

( Z )- N -Benzylidene-2-methoxy-2-oxoethanamine Oxide (1a)

White solid; yield: 5.10 g (88%); mp 110-112 ˚C.

¹H NMR (400 MHz, CDCl3): δ = 3.77 (s, 3 H), 4.71 (s, 2 H), 7.38-7.41 (m, 3 H), 7.44 (s, 1 H), 8.20-8.30 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 53.0, 67.9, 128.5, 128.9, 130.1, 131.1, 137.4, 166.2.

HRMS: m/z [M + Na]+ calcd for C10H11NNaO3: 216.0637; found: 216.0639.

Anal. Calcd for C10H11NO3: C, 62.17; H, 5.74; N, 7.25. Found: C, 62.34; H, 5.61; N, 7.48.

( Z )-2-Methoxy- N -(4-methoxybenzylidene)-2-oxoethanamine Oxide (1b)

Oil; yield: 6.03 g (90%).

¹H NMR (400 MHz, CDCl3): δ = 3.79 (s, 3 H), 3.81 (s, 3 H), 4.68 (s, 2 H), 6.85-6.88 (m, 2 H), 7.39 (s, 1 H), 8.20-8.22 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 50.1, 52.5, 67.9, 113.0, 123.1, 128.9, 137.4, 160.7, 165.8.

HRMS: m/z [M + Na]+ calcd for C11H13NNaO4: 246.0742; found: 246.0741.

Anal. Calcd for C11H13NO4: C, 59.19; H, 5.87; N, 6.27. Found: C, 59.48; H, 6.23; N, 6.01.

( Z )- N -(4-Bromobenzylidene)-2-methoxy-2-oxoethanamine Oxide­ (1c)

White solid; yield: 6.53 g (80%); mp 96-98 ˚C.

¹H NMR (400 MHz, CDCl3): δ = 3.83 (s, 3 H), 4.74 (s, 2 H), 7.41 (s, 1 H), 7.55-7.57 (m, 2 H), 8.11-8.13 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 53.2, 68.0, 128.1, 128.8, 130.2, 131.7, 136.4, 166.0.

HRMS: m/z [M + Na]+ calcd for C10H10BrNNaO3: 293.9742; found: 293.9744.

Anal. Calcd for C10H10BrNO3: C, 44.14; H, 3.70; N, 5.1. Found: C, 44.42; H, 3.48; N, 4.89.

( Z )- N -(4-Chlorobenzylidene)-2-methoxy-2-oxoethanamine Oxide­ (1d)

White solid; yield: 5.40 g (79%); mp 75-77 ˚C.

¹H NMR (400 MHz, CDCl3): δ = 3.83 (s, 3 H), 4.74 (s, 2 H), 7.41 (s, 1 H), 7.45-7.47 (m, 2 H), 8.13-8.15 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 53.1, 67.9, 128.3, 128.9, 130.1 (2 C), 136.3, 166.2.

HRMS: m/z [M + Na]+ calcd for C10H10ClNNaO3: 250.0247; found: 250.0251.

Anal. Calcd for C10H10ClNO3: C, 52.76; H, 4.43; N, 6.15. Found: C, 52.57; H, 4.21; N, 5.96.

( Z )-2-Methoxy- N -(4-methylbenzylidene)-2-oxoethanamine Oxide­ (1e)

Oil; yield: 5.28 g (85%).

¹H NMR (400 MHz, CDCl3): δ = 2.42 (s, 3 H), 3.86 (s, 3 H), 4.76 (s, 2 H), 7.26-7.29 (m, 2 H), 7.43 (s, 1 H), 8.17-8.19 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 22.0, 53.1, 67.8, 127.3, 129.0, 129.3, 137.6, 141.9, 166.2.

HRMS: m/z [M + Na]+ calcd for C11H13NNaO3: 230.0793; found: 230.0790.

Anal. Calcd for C11H13NO3: C, 63.76; H, 6.32; N, 6.76. Found: C, 63.90; H, 6.48; N, 6.88.

( Z )- N -(Biphenyl-4-ylmethylene)-2-methoxy-2-oxoethanamine Oxide (1f)

White solid; yield: 5.57 g (69%); mp 118-120 ˚C.

¹H NMR (400 MHz, CDCl3): δ = 3.86 (s, 3 H), 4.78 (s, 2 H), 7.41 (s, 1 H), 7.43-7.49 (m, 3 H), 7.60-7.65 (m, 2 H), 7.67-7.71 (m, 2 H), 8.22-8.26 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 53.1, 68.0, 127.1, 128.0, 128.9, 129.3, 136.1, 136.9, 140.2, 141.1, 143.7, 166.1.

HRMS: m/z [M + Na]+ calcd for C16H15NNaO3: 292.0950; found: 292.0951.

Anal. Calcd for C16H15NO3: C, 71.36; H, 5.61; N, 5.20. Found: C, 71.46; H, 5.83; N, 5.02.

( Z )-2-Methoxy- N -(4-nitrobenzylidene)-2-oxoethanamine Oxide (1g)

Oil; yield: 5.72 g (80%).

¹H NMR (400 MHz, CDCl3): δ = 3.86 (s, 3 H), 4.80 (s, 2 H), 7.57 (s, 1 H), 8.25-8.31 (m, 2 H), 8.39-8.43 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 53.3, 68.5, 122.4, 129.2, 135.1, 135.4, 148.2, 165.6.

HRMS: m/z [M + H]+ calcd for C10H11N2O5: 239.0668; found: 239.0670.

Anal. Calcd for C10H10N2O5: C, 50.42; H, 4.23; N, 11.76. Found: C, 50.19; H, 4.47; N, 11.50.

( Z )- N -(4-Cyanobenzylidene)-2-methoxy-2-oxoethanamine Oxide­ (1h)

White solid; yield: 5.43 g (83%); mp 132-134 ˚C.

¹H NMR (400 MHz, CDCl3): δ = 3.84 (s, 3 H), 4.78 (s, 2 H), 7.35 (s, 1 H), 7.60-7.62 (m, 2 H), 8.24-8.26 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 53.2, 68.4, 113.1, 118.4, 128.7, 132.2, 133.8, 135.4, 165.4.

HRMS: m/z [M + Na]+ calcd for C11H10N2NaO3: 241.0589; found: 241.0586.

Anal. Calcd for C11H10N2O3: C, 60.55; H, 4.62; N, 12.84. Found: C, 60.29; H, 4.87; N, 12.68.

( Z )-2-Methoxy- N -(naphthalen-1-ylmethylene)-2-oxoethan­amine Oxide (1i)

White solid; yield: 4.74 g (65%); mp 121-123 ˚C.

¹H NMR (400 MHz, CDCl3): δ = 3.87 (s, 3 H), 4.89 (s, 2 H), 7.54-7.60 (m, 4 H), 7.89-7.91 (m, 1 H), 7.93-7.96 (m, 1 H), 8.00-8.22 (m, 1 H), 8.23 (s, 1 H).

¹³C NMR (100 MHz, CDCl3): δ = 53.2, 68.7, 121.6, 125.7, 126.0, 127.1, 127.3, 128.7, 129.4, 131.7, 133.1 (2 C), 135.8, 166.2.

HRMS: m/z [M + Na]+ calcd for C14H13NNaO3: 266.0793; found: 266.0796.

Anal. Calcd for C14H13NO3: C, 69.12; H, 5.39; N, 5.76. Found: C, 69.38; H, 5.57; N, 5.84.

( Z )- N -Benzylidene-2-(benzyloxy)-2-oxoethanamine Oxide (1j)

White solid; yield: 7.19 g (89%); mp 80-82 ˚C.

¹H NMR (400 MHz, CDCl3): δ = 4.63 (s, 2 H), 5.11 (s, 2 H), 7.25-7.38 (m, 8 H), 7.45 (s, 1 H), 8.11-8.19 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 67.7, 68.0, 128.5 (2 C), 128.6, 128.7, 128.9, 129.1, 131.0, 134.8, 137.5, 165.7.

HRMS: m/z [M + Na]+ calcd for C16H15NNaO3: 292.0950; found: 292.0949.

Anal. Calcd for C16H15NO3: C, 71.36; H, 5.61; N, 5.20. Found: C, 71.48; H, 5.87; N, 5.35.

( Z )-2-(Benzyloxy)- N -(4-methoxybenzylidene)-2-oxoethan­amine Oxide (1k)

White solid; yield: 7.27 g (81%); mp 75-77 ˚C.

¹H NMR (400 MHz, CDCl3): δ = 3.82 (s, 3 H), 4.72 (s, 2 H), 5.23 (s, 2 H), 6.90-6.92 (m, 2 H), 7.30 (s, 1 H), 7.26-7-32 (m, 5 H), 8.20-8.23 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 55.4, 67.6, 68.1, 114.0, 131.2, 122.8, 128.5, 128.6, 131.5, 134.9, 137.6, 161.7, 165.8.

HRMS: m/z [M + Na]+ calcd for C17H17NNaO4: 322.1055; found: 322.1052.

Anal. Calcd for C17H17NO4: C, 68.21; H, 5.72; N, 4.68. Found: C, 68.00; H, 5.93; N, 4.31.

( Z )- N -Benzylidene-2-ethoxy-2-oxoethanamine Oxide (1l)

Oil; yield: 5.72 g (92%).

¹H NMR (400 MHz, CDCl3): δ 1.31 (t, J = 7.3 Hz, 3 H), 4.30 (q, J = 7.3 Hz, 2 H), 4.72 (s, 2 H), 7.43 (s, 1 H), 7.45-7.50 (m, 3 H), 8.23-8.26 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 14.1, 62.4, 68.1, 128.6, 128.9, 130.2, 131.1, 137.3, 165.7.

HRMS: m/z [M + Na]+ calcd for C11H13NNaO3: 230.0793; found: 230.0794.

Anal. Calcd for C11H13NO3: C, 63.76; H, 6.32; N, 6.76. Found: C, 63.90; H, 6.27; N, 6.97.

Transoximation of Nitrones To Give 7a,b and 14a,b; General Procedure

To a cooled (0 ˚C) soln of NH2OH˙HCl (6.32 g, 90.8 mmol) in MeOH (100 mL), NaOH (3.64 g, 90.8 mmol) and AcOH (5.45 g, 5.4 mL, 90.8 mmol) were added sequentially. The resulting soln was stirred for 15 min at which time the corresponding nitrone 1a,j (30.2 mmol) was added; the mixture was heated under reflux for 16 h. After concentration under reduced pressure a 6 M KOH saturated with NaCl was added until pH 7. The resulting mixture was extracted with EtOAc (3 × 120 mL). The combined organic extracts were dried (MgSO4), filtered, and evaporated under reduced pressure. The resulting residue was used in the next step without further purification. An analytical sample can be obtained by purifying the crude product by radial chromatography (hexane-EtOAc, 7:3).

Methyl 2-(Hydroxyamino)acetate (7a)

Oil; yield: 1.91 g (60%).

¹H NMR (400 MHz, CDCl3): δ = 3.63 (s, 2 H), 3.72 (s, 3 H), 5.50-6.30 (br s, 2 H, ex. D2O).

¹³C NMR (100 MHz, CDCl3): δ = 52.2, 54.8, 171.6.

Anal. Calcd for C3H7NO3: C, 34.29; H, 6.71; N, 13.33. Found: C, 34.04; H, 6.94; N, 13.17.

Benzyl 2-(Hydroxyamino)acetate (7b)

Sticky foam; yield: 3.39 g (62%).

¹H NMR (400 MHz, CDCl3): δ = 3.67 (s, 2 H), 5.15 (s, 2 H), 5.60-6.10 (br s, 2 H, ex. D2O), 7.28-7.32 (m, 5 H).

¹³C NMR (100 MHz, CDCl3): δ = 58.2, 65.4, 127.3, 127.9, 129.0, 136.3, 167.3.

Anal. Calcd for C9H11NO3: C, 59.66; H, 6.12; N, 7.73. Found: C, 60.21; H, 6.35; N, 7.67.

( S )- N -[1-(Benzyloxy)-3-methylbutan-2-yl]hydroxylamine (14a)

Oil; yield: 5.69 g (90%); R f  = 0.30 (hexane-EtOAc, 7:3).

[α]D ²5 -11 (c 1.00, CHCl3) [Lit. [¹³d] [α]D ²5 -11.2 (c 1.29, CHCl3)].

¹H NMR (400 MHz, CDCl3): δ = 0.91 (d, J = 6.9 Hz, 3 H), 0.98 (d, J = 6.9 Hz, 3 H), 1.93 (qqd, J = 6.9, 6.9, 6.3 Hz, 1 H), 2.82 (ddd, J = 7.3, 6.3, 3.6 Hz, 1 H), 3.50 (dd, J = 9.6, 7.3 Hz, 1 H), 3.64 (dd, J = 9.6, 3.6 Hz, 1 H), 4.51-4.57 (m, 2 H, AB system), 4.93-5.84 (br s, 2 H), 7.27-7.39 (m, 5 H).

¹³C NMR (100 MHz, CDCl3): δ = 18.1, 19.4, 31.0, 55.9, 73.2, 74.1, 127.5, 127.6, 128.2.

Anal. Calcd for C12H19NO2: C, 68.87; H, 9.15; N, 6.69. Found: C, 68.63; H, 9.36; N, 6.48.

( R )- N -[2-(Benzyloxy)-1-phenylethyl]hydroxylamine (14b)

Oil; yield: 6.83 g (93%); R f  = 0.26 (hexane-EtOAc, 7:3).

[α]D ²5 -22 (c 1.00, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 3.59-3.74 (m, 2 H), 4.26 (dd, J = 8.2, 4.3 Hz, 1 H), 4.55 (s, 2 H), 5.25-6.39 (br s, 2 H), 7.24-7.41 (m, 10 H).

¹³C NMR (100 MHz, CDCl3): δ = 65.4, 71.5, 73.3, 127.7, 127.8, 127.9, 128.3, 128.5, 128.6, 137.8, 138.7.

Anal. Calcd for C15H17NO2: C, 74.05; H, 7.04; N, 5.76. Found: C, 74.27; H, 7.24; N, 5.53.

Synthesis of Nitrones 1m-o; General Procedure

A soln of hydroxylamine 7a (4.2 g, 40 mmol) or 7b (7.25 g, 40 mmol) in CH2Cl2 (70 mL) was treated with the corresponding aldehyde (pivaldehyde or 2-methylpropanal, 40 mmol) and MgSO4 (4.82 g, 40 mmol). The resulting mixture was stirred at r.t. for 4 h, filtered and evaporated under reduced pressure. The crude product was purified by column chromatography (hexane-EtOAc, 4:1).

( Z )-2-Methoxy- N -(2-methylpropylidene)-2-oxoethanamine Oxide­ (1m)

Oil; yield: 5.86 g (92%).

¹H NMR (400 MHz, CDCl3): δ = 1.14 (d, J = 7.1 Hz, 6 H), 3.2 (m, 1 H), 3.81 (s, 3 H), 4.52 (s, 2 H), 6.59 (d, J = 6.6 Hz, 1 H).

¹³C NMR (100 MHz, CDCl3): δ = 18.7 (2 C), 26.3, 53.0, 66.2, 148.2, 166.13.

HRMS: m/z [M + H]+ calcd for C7H14NO3: 160.0974; found: 160.0975.

Anal. Calcd for C7H13NO3: C, 52.82; H, 8.23; N, 8.80. Found: C, 52.69; H, 8.46; N, 8.78.

( Z )- N -(2,2-Dimethylpropylidene)-2-methoxy-2-oxoethanamine Oxide (1n)

Oil; yield: 6.51 g (94%).

¹H NMR (400 MHz, CDCl3): δ = 1.24 (s, 9 H), 3.75 (s, 3 H), 4.45 (s, 2 H), 6.48 (s, 1 H).

¹³C NMR (100 MHz, CDCl3): δ = 14.2, 25.8 (3 C), 53.0, 67.5, 148.4, 166.3.

HRMS: m/z [M + H]+ calcd for C8H16NO3: 174.1130; found: 174.1132.

Anal. Calcd for C8H15NO3: C, 55.47; H, 8.73; N, 8.09. Found: C, 55.23; H, 8.65; N, 8.25.

( Z )-2-(Benzyloxy)- N -(2,2-dimethylpropylidene)-2-oxoethan­amine Oxide (1o)

Oil; yield: 9.17 g (92%).

¹H NMR (400 MHz, CDCl3): δ = 1.19 (s, 9 H), 4.44 (s, 2 H), 5.13 (s, 2 H), 6.43 (s, 1 H), 7.25-7.29 (m, 5 H).

¹³C NMR (100 MHz, CDCl3): δ = 14.2, 25.8 (3 C), 67.8, 67.9, 127.9, 128.1, 128.7, 135.7, 148.6, 167.1.

HRMS: m/z [M + H]+ calcd for C14H20NO3: 250.1443; found: 250.1442.

Anal. Calcd for C14H19NO3: C, 67.45; H, 7.68; N, 5.62. Found: C, 67.59; H, 7.49; N, 5.71.

O -Benzyl Amino Alcohols 12a-c; General Procedure

To a soln of the amino alcohol (97 mmol) in THF (75 mL), NaH (4.82 g of a 60% dispersion in mineral oil, 144 mmol) was added and the resulting suspension was stirred at r.t. for 15 min and at reflux for 30 min. BnCl (12.2 g, 11 mL, 96 mmol) was added and the mixture was refluxed for an additional 48 h. The mixture was cooled to r.t. and NaOMe (1.08 g, 20 mmol) was added in one portion. After stirring for 30 min, H2O (10 mL) was added carefully and the solvent was evaporated under reduced pressure. The residue was partitioned between 6 M KOH saturated with NaCl (50 mL) and CH2Cl2 (50 mL). The organic layer was separated and the aqueous layer was extracted with CH2Cl2 (3 × 40 mL). The combined organic extracts were dried (MgSO4), filtered, and evaporated under reduced pressure to give the crude product which was purified by column chromatography.

2-(Benzyloxy)ethanamine (12a)

Oil; yield: 13.2 g (90%); R f  = 0.38 (EtOAc-MeOH-Et3N, 94:5:1).

¹H NMR (400 MHz, CDCl3): δ = 1.50 (br s, 2 H, ex. D2O), 2.90 (t, J = 5.2 Hz, 2 H), 3.53 (t, J = 5.2 Hz, 2 H), 4.56 (s, 2 H), 7.28-7.36 (m, 5 H).

¹³C NMR (100 MHz, CDCl3): δ = 41.8, 72.5, 73.1, 127.7, 128.4, 128.5, 138.3.

HRMS: m/z [M + H]+ calcd for C9H14NO3: 184.0974; found: 184.0973.

Anal. Calcd for C9H13NO: C, 71.49; H, 8.67; N, 9.26. Found: C, 71.64; H, 8.83; N, 8.97.

( S )-1-(Benzyloxy)-3-methylbutan-2-amine (12b)

Oil; yield: 17.1 g (91%); R f  = 0.33 (EtOAc-MeOH-Et3N, 90:9:1).

[α]D ²5 +19 (c 1.00, CHCl3) [Lit. [¹³d] (for enantiomer) [α]D ²5 -14.2 (c 1.58, CHCl3)].

¹H NMR (400 MHz, CDCl3): δ = 0.90 (d, J = 6.7 Hz, 3 H), 0.91 (d, J = 6.8 Hz, 3 H), 1.45 (br s, 2 H), 1.65 (qqd, J = 6.8, 6.7, 6.2 Hz, 1 H), 2.78 (ddd, J = 8.2, 6.2, 3.8 Hz, 1 H), 3.30 (dd, J = 9.0, 8.2 Hz, 1 H), 3.52 (dd, J = 9.0, 3.8 Hz, 1 H), 4.49-4.57 (m, 2 H), 7.40-7.24 (m, 5 H).

¹³C NMR (100 MHz, CDCl3): δ = 17.9, 19.2, 30.7, 56.1, 73.0, 73.8, 127.3, 127.4, 128.2, 138.2.

HRMS: m/z [M + H]+ calcd for C12H20NO: 194.1539; found: 194.1540.

Anal. Calcd for C12H19NO: C, 74.57; H, 9.91; N, 7.25. Found: C, 74.78; H, 10.11; N, 7.05.

( R )-2-(Benzyloxy)-1-phenylethanamine (12c)

Oil; yield: 18.08 g (82%); R f  = 0.24 (EtOAc-MeOH-Et3N, 94:5:1).

[α]D ²5 +20 (c 0.98, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 1.81 (br s, 2 H), 3.46 (dd, J = 9.2, 8.9 Hz, 1 H), 3.61 (dd, J = 9.2, 3.8 Hz, 1 H), 4.24 (dd, J = 8.9, 3.8 Hz, 1 H), 4.49-4.60 (m, 2 H), 7.21-7.42 (m, 10 H).

¹³C NMR (100 MHz, CDCl3): δ = 55.5, 73.1, 73.5, 126.7, 127.3, 127.5, 127.6, 128.3, 138.0, 142.3.

HRMS: m/z [M + H]+ calcd for C15H18NO: 228.1383; found: 228.1378.

Anal. Calcd for C15H17NO: C, 79.26; H, 7.54; N, 6.16. Found: C, 79.13; H, 7.68; N, 6.39.

Nitrones 2a-k; General Procedure

A suspension of the corresponding O-benzyl amino alcohol 12a-c (30 mmol) in CH2Cl2 (50 mL) was treated with MgSO4 (3.61 g, 30 mmol) and the corresponding aldehyde (30 mmol). The resulting mixture was stirred at r.t. for 16 h. The mixture was filtered through a pad of Celite and washed with EtOAc and the filtrate was evaporated under reduced pressure to give crude imine 13, which was taken up in MeOH (40 mL) and treated sequentially with MgSO4 (3.61 g, 30 mmol), MeReO3 (0.15 g, 0.56 mmol) and UHP (8.50 g, 90 mmol). The resulting mixture was stirred for the stated time (see Table  [²] ) at r.t., filtered, and evaporated under reduced pressure. The crude product was purified by column chromatography (hexane-EtOAc, 1:1).

( Z )- N -Benzylidene-2-(benzyloxy)ethanamine Oxide (2a)

White solid; yield: 6.89 g (90%); mp 96-98 ˚C.

¹H NMR (400 MHz, CDCl3): δ = 3.92 (t, J = 4.4 Hz, 2 H), 4.10 (t, J = 4.4 Hz, 2 H), 4.51 (s, 2 H), 7.25-7.39 (m, 10 H), 7.40 (s, 1 H).

¹³C NMR (100 MHz, CDCl3): δ = 65.2, 67.4, 72.3, 127.8, 127.9, 128.4 128.7 (2 C), 128.9, 133.3, 135.1, 146.9.

HRMS: m/z [M + Na]+ calcd for C16H17NNaO2: 278.1157; found: 278.1159.

Anal. Calcd for C16H17NO2: C, 75.27; H, 6.71; N, 5.49. Found: C, 75.03; H, 6.83; N, 5.50.

( Z )-2-(Benzyloxy)- N -(4-nitrobenzylidene)ethanamine Oxide (2b)

Red crystals; yield: 8.29 g (92%); mp 132-134 ˚C.

¹H NMR (400 MHz, CDCl3): δ = 3.98 (t, J = 4.6 Hz, 2 H), 4.14 (t, J = 4.6 Hz, 2 H), 4.55 (s, 2 H), 7.22-7.34 (m, 5 H), 7.55 (s, 1 H), 8.23-8.26 (m, 2 H), 8.36-8.40 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 65.9, 68.1, 73.5, 123.7, 127.7, 127.9, 128.5, 128.9, 133.5, 135.9, 137.4, 147.3.

HRMS: m/z [M + Na]+ calcd for C16H16N2NaO4: 323.1008; found: 323.1007.

Anal. Calcd for C16H16N2O4: C, 63.99; H, 5.37; N, 9.33. Found: C, 64.23; H, 5.16; N, 9.19.

( Z )-2-(Benzyloxy)- N -(4-methoxybenzylidene)ethanamine Oxide­ (2c)

Oil; yield: 7.79 g (91%).

¹H NMR (400 MHz, CDCl3): δ = 3.60 (t, J = 4.9 Hz, 2 H), 3.92 (s, 3 H), 4.21 (t, J = 4.9 Hz, 2 H), 4.65 (s, 2 H), 6.88-6.90 (m, 2 H), 7.20-7.25 (m, 2 H), 7.32 (s, 1 H), 7.34-7.46 (m, 5 H).

¹³C NMR (100 MHz, CDCl3): δ = 56.9, 64.5, 67.3, 74.1, 115.7, 123.9, 124.3, 127.6, 127.9, 128.8, 136.5, 147.8, 156.4.

HRMS: m/z [M + Na]+ calcd for C17H19NNaO3: 308.1263; found: 308.1260.

Anal. Calcd for C17H19NO3: C, 71.56; H, 6.71; N, 4.91. Found: C, 71.79; H, 6.94; N, 4.78.

(S,Z)- N -Benzylidene-1-(benzyloxy)-3-methylbutan-2-amine Oxide (2d)

White solid; yield: 7.58 g (85%); mp 79-81 ˚C; R f  = 0.23 (hexane-EtOAc, 7:3).

[α]D ²5 +29 (c 1.00, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 1.00 (d, J = 6.8 Hz, 3 H), 1.01 (d, J = 7.0 Hz, 3 H), 2.26 (dqq, J = 9.3, 7.0, 6.8 Hz, 1 H), 3.66 (ddd, J = 9.3, 9.3, 2.9 Hz, 1 H), 3.76 (dd, J = 10.2, 2.9 Hz, 1 H), 4.10 (dd, J = 10.2, 9.3 Hz, 1 H), 4.49 (d, J = 11.9 Hz, 1 H), 4.59 (d, J = 11.9 Hz, 1 H), 7.21-7.31 (m, 5 H), 7.40-7.47 (m, 4 H), 8.26-8.31 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 19.3, 19.6, 28.0, 68.6, 73.4, 83.1, 127.5, 128.3, 128.4, 128.7, 130.1, 130.4, 135.1, 137.9.

HRMS: m/z [M + Na]+ calcd for C19H23NaNO2: 320.1621; found: 320.1616.

Anal. Calcd for C19H23NO2: C, 76.73; H, 7.80; N, 4.71. Found: C, 76.92; H, 7.96; N, 4.92.

(S,Z)-1-(Benzyloxy)-3-methyl- N -(4-nitrobenzylidene)butan-2-amine Oxide (2e)

Yellow oil; yield: 9.04 g (88%); R f  = 0.22 (hexane-EtOAc, 4:1).

[α]D ²5 +49 (c 1.00, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 0.99 (d, J = 6.6 Hz, 3 H), 1.03 (d, J = 6.8 Hz, 3 H), 2.20-2.30 (m, 1 H), 3.72-3.84 (m, 2 H), 4.03-4.09 (m, 1 H), 4.50 (d, J = 12.0 Hz, 1 H), 4.57 (d, J = 12.0 Hz, 1 H), 7.19-7.35 (m, 5 H), 7.57 (s, 1 H), 8.23-8.29 (m, 2 H), 8.41-8.47 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 19.3, 19.5, 28.1, 68.5, 73.4, 84.0, 123.6, 127.5, 128.3, 128.9, 130.9, 133.3, 136.0, 137.7, 147.5.

HRMS: m/z [M + Na]+ calcd for C19H22N2NaO4: 365.1472; found: 365.1483.

Anal. Calcd for C19H22N2O4: C, 66.65; H, 6.48; N, 8.18. Found: C, 66.41; H, 6.57; N, 8.35.

(S,Z)-1-(Benzyloxy)- N -(4-methoxybenzylidene)-3-methyl­butan-2-amine Oxide (2f)

White solid; yield: 8.94 g (91%); mp 102-104 ˚C; R f  = 0.26 (hexane-EtOAc, 4:1).

[α]D ²5 +43 (c 1.00, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 0.90 (d, J = 6.7 Hz, 3 H), 0.92 (d, J = 6.9 Hz, 3 H), 2.17 (dqq, J = 9.6, 6.9, 6.7 Hz, 1 H), 3.52 (ddd, J = 9.6, 9.2, 2.9 Hz, 1 H), 3.66 (dd, J = 10.2, 2.9 Hz, 1 H), 3.76 (s, 3 H), 4.01 (dd, J = 10.2, 9.2 Hz, 1 H), 4.40 (d, J = 11.9 Hz, 1 H), 4.50 (d, J = 11.9 Hz, 1 H), 6.83-6.89 (m, 2 H), 7.13-7.22 (m, 5 H), 7.26 (s, 1 H), 8.17-8.23 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 19.3, 19.7, 27.9, 55.2, 73.4, 82.6, 113.7, 123.4, 127.5, 127.5, 128.3, 138.0, 160.7.

HRMS: m/z [M + H]+ calcd for C20H26NO3: 328.1907; found: 328.1910.

Anal. Calcd for C20H25NO3: C, 73.37; H, 7.70; N, 4.28. Found: C, 73.54; H, 7.56; N, 4.12.

(S,Z)-1-(Benzyloxy)- N -(furan-2-ylmethylene)-3-methylbutan-2-amine Oxide (2g)

White solid; yield: 7.50 g (87%); mp 87-89 ˚C; R f  = 0.42 (hexane-EtOAc, 7:3).

[α]D ²5 +33 (c 1.25, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 0.97 (d, J = 6.6 Hz, 3 H), 1.01 (d, J = 6.8 Hz, 3 H), 2.19-2.29 (m, 1 H), 3.63 (dt, J = 9.2, 2.9 Hz, 1 H), 3.74 (dd, J = 10.2, 2.9 Hz, 1 H), 4.05 (dd, J = 10.2, 9.2 Hz, 1 H), 4.49 (d, J = 12.0 Hz, 1 H), 4.59 (d, J = 12.0 Hz, 1 H), 6.58 (ddd, J = 3.4, 1.8, 0.5 Hz, 1 H), 7.23-7.35 (m, 5 H), 7.50 (dd, J = 1.8, 0.5 Hz, 1 H), 7.60 (s, 1 H), 7.83 (d, J = 3.4 Hz, 1 H).

¹³C NMR (100 MHz, CDCl3): δ = 19.4, 19.7, 28.1, 68.5, 73.4, 76.7, 77.3, 81.8, 112.2, 115.2, 126.2, 127.6, 127.6, 128.3, 137.9 (C4), 143.3, 146.7.

HRMS: m/z [M + Na]+ calcd for C17H21NNaO3: 310.1414; found: 310.1422.

Anal. Calcd for C17H21NO3: C, 71.06; H, 7.37; N, 4.87. Found: C, 71.31; H, 7.39; N, 5.11.

(R,Z)- N -Benzylidene-2-(benzyloxy)-1-phenylethanamine Oxide­ (2h)

White solid; yield: 8.55 g (86%); mp 72-74 ˚C; R f  = 0.14 (hexane-EtOAc, 4:1).

[α]D ²5 +20 (c 1.00, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 3.85 (dd, J = 10.3, 3.7 Hz, 1 H), 4.59 (dd, J = 10.3, 9.4 Hz, 1 H), 4.56 (d, J = 12.0 Hz, 1 H), 4.70 (d, J = 12.0 Hz, 1 H), 5.16 (dd, J = 9.4, 3.7 Hz, 1 H), 7.21-7.34 (m, 5 H), 7.32-7.39 (m, 3 H), 7.40-7.45 (m, 3 H), 7.50-7.55 (m, 2 H), 7.57 (s, 1 H), 8.23-8.29 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 69.6, 73.7, 79.4, 127.7, 127.8 (2 C), 128.3, 128.4, 128.7, 128.9, 129.1, 130.3, 130.5, 134.6, 135.3, 137.8.

HRMS: m/z [M + H]+ calcd for C22H22NO2: 332.1645; found: 332.1653.

Anal. Calcd for C22H21NO2: C, 79.73; H, 6.39; N, 4.23. Found: C, 79.90; H, 6.55; N, 4.48.

(R,Z)-2-(Benzyloxy)- N -(4-nitrobenzylidene)-1-phenylethan­amine Oxide (2i)

Yellow oil; yield: 10.39 g (92%); R f  = 0.15 (hexane-EtOAc, 4:1).

[α]D ²5 +53 (c 1.00, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 3.81 (dd, J = 10.2, 3.4 Hz, 1 H), 4.56 (dd, J = 10.2, 9.7 Hz, 1 H), 4.56 (d, J = 12.0 Hz, 1 H), 4.68 (d, J = 12.0 Hz, 1 H), 5.20 (dd, J = 9.7, 3.4 Hz, 1 H), 7.22-7.34 (m, 4 H), 7.35-7.43 (m, 4 H), 7.45-7.51 (m, 2 H), 7.68 (s, 1 H), 8.20-8.29 (m, 2 H), 8.36-8.43 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 69.6, 73.6, 80.3, 123.6, 127.7, 127.8, 127.8, 128.3, 128.8, 128.9, 129.3, 132.7, 134.0, 136.0, 137.5, 147.6.

HRMS: m/z [M + Na]+ calcd for C22H20N2NaO4: 339.1315; found: 339.1319.

Anal. Calcd for C22H20N2O4: C, 70.20; H, 5.36; N, 7.44. Found: C, 70.06; H, 5.53; N, 7.29.

(R,Z)-2-(Benzyloxy)- N -(4-methoxybenzylidene)-1-phenylethan­amine Oxide (2j)

White solid; yield: 9.76 g (90%); mp 112-114 ˚C; R f  = 0.30 (hexane-EtOAc, 7:3).

[α]D ²5 +29 (c 1.07, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 3.84 (s, 3 H), 3.88 (dd, J = 10.5, 3.7 Hz, 1 H), 4.59 (d, J = 11.9 Hz, 1 H), 4.64 (dd, J = 10.5, 9.1 Hz, 1 H), 4.73 (d, J = 11.9 Hz, 1 H), 5.17 (dd, J = 9.1, 3.7 Hz, 1 H), 6.92-6.97 (m, 2 H), 7.26-7.43 (m, 8 H), 7.53-7.60 (m, 3 H), 8.25-8.35 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 55.2, 69.5, 73.5, 78.7, 113.7, 123.2, 127.6, 127.7, 127.8, 128.3, 128.5, 128.8, 130.9, 134.6, 135.1, 137.7, 161.1.

HRMS: m/z [M + Na]+ calcd for C23H23NNaO3: 384.1570; found: 384.1571.

Anal. Calcd for C23H23NO3: C, 76.43; H, 6.41; N, 3.88. Found: C, 76.68; H, 6.71; N, 3.96.

(R,Z)-2-(Benzyloxy)- N -(furan-2-ylmethylene)-1-phenylethan­amine Oxide (2k)

Oil; yield: 8.19 g (85%).

[α]D ²5 +38 (c 1.07, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 3.83 (dd, J = 10.6, 3.9 Hz, 1 H), 4.52 (dd, J = 10.6, 9.1 Hz, 1 H), 4.60 (d, J = 12.1 Hz, 1 H), 4.68 (d, J = 12.1 Hz, 1 H), 5.08 (dd, J = 9.1, 3.9 Hz, 1 H), 6.48-6.59 (m, 2 H), 7.21-7.39 (m, 8 H), 7.43 (s, 1 H), 7.46-7.49 (m, 2 H), 7.86 (m, 1 H).

¹³C NMR (100 MHz, CDCl3): δ = 68.8, 73.5, 79.1, 109.5, 111.6, 127.7, 127.8, 127.9, 128.5, 128.6, 131.2, 134.5, 137.3, 140.9 141.2, 143.5.

HRMS: m/z [M + Na]+ calcd for C20H19NNaO3: 344.1263; found: 344.1261.

Anal. Calcd for C20H19NO3: C, 74.75; H, 5.96; N, 4.36. Found: C, 74.63; H, 6.17; N, 4.28.

Nitrones 2l-z; General Procedure

A soln of hydroxylamine 14a (6.28 g, 30 mmol) or 14b (7.30 g, 30 mmol) in CH2Cl2 (60 mL) was treated with the corresponding aldehyde (30 mmol) and MgSO4 (3.61 g, 30 mmol). The resulting mixture was stirred at r.t. for 4 h, filtered, and evaporated under reduced pressure. The crude product was purified by column chromatography (hexane-EtOAc, 4:1).

(S,Z)-1-(Benzyloxy)- N -ethylidene-3-methylbutan-2-amine Oxide­ (2l)

Oil; yield: 5.72 g (81%).

[α]D ²5 -2.72 (c 0.90, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 0.90 (d, J = 6.7 Hz, 3 H), 0.93 (d, J = 6.9 Hz, 3 H), 2.01 (d, J = 5.8 Hz, 3 H), 2.09-2.23 (m, 1 H), 3.45 (ddd, J = 9.6, 9.3, 2.8 Hz, 1 H), 3.63 (dd, J = 10.1, 2.8 Hz, 1 H), 3.99 (dd, J = 10.1, 9.6 Hz, 1 H), 4.44 (d, J = 11.9 Hz, 1 H), 4.56 (d, J = 11.9 Hz, 1 H), 6.76 (t, J = 5.9 Hz, 1 H), 7.22-7.31 (m, 5 H).

¹³C NMR (100 MHz, CDCl3): δ = 12.3, 19.1, 19.5, 27.3, 68.1, 73.2, 81.2, 127.4, 127.4, 128.2, 134.9, 137.9.

HRMS: m/z [M + H]+ calcd for C14H22NO2: 236.1645; found: 236.1649.

Anal. Calcd for C14H21NO2: C, 71.46; H, 8.99; N, 5.95. Found: C, 71.58; H, 8.76; N, 5.84.

(S,Z)-1-(Benzyloxy)-3-methyl- N -(2-methylpropylidene)butan-2-amine Oxide (2m)

Oil; yield: 6.72 g (85%); R f  = 0.17 (hexane-EtOAc, 7:3).

[α]D ²5 -5 (c 1.12, CHCl3) [Lit. [¹³d] (for enantiomer) [α]D ²5 +2 (c 1.38, CHCl3)].

¹H NMR (400 MHz, CDCl3): δ = 0.89-0.94 (m, 6 H), 1.09 (dt, J = 6.9, 2.5 Hz, 6 H), 2.06-2.20 (m, 1 H), 3.13-3.26 (m, 1 H), 3.37 (ddd, J = 9.4, 9.4, 2.6 Hz, 1 H), 3.63 (dd, J = 10.1, 2.6 Hz, 1 H), 3.99 (dd, J = 10.1, 9.4 Hz, 1 H), 4.45 (d, J = 11.8 Hz, 1 H), 4.55 (d, J = 11.8 Hz, 1 H), 6.50 (d, J = 7.2 Hz, 1 H), 7.20-7.32 (m, 5 H).

¹³C NMR (100 MHz, CDCl3): δ = 18.7, 18.8, 19.1, 19.3, 25.5, 27.2, 68.2, 73.1, 81.2, 127.2, 127.3, 128.0, 138.0, 145.1.

HRMS: m/z [M + H]+ calcd for C16H26NO2: 264.1958; found: 264.1968.

Anal. Calcd for C16H25NO2: C, 72.96; H, 9.57; N, 5.32. Found: C, 73.12; H, 9.68; N, 5.36.

(S,Z)-1-(Benzyloxy)- N -butylidene-3-methylbutan-2-amine Oxide­ (2n)

Oil; yield: 7.51 g (95%); R f  = 0.24 (hexane-EtOAc, 7:3).

[α]D ²5 -7 (c 1.01, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 0.89-0.99 (m, 9 H), 1.54 (q, J = 7.5 Hz, 2 H), 2.09-2.22 (m, 1 H), 2.45-2.52 (m, 2 H), 3.43 (ddd, J = 9.4, 9.3, 2.9 Hz, 1 H), 3.64 (dd, J = 10.1, 2.9 Hz, 1 H), 3.99 (dd, J = 10.1, 9.6 Hz, 1 H), 4.45 (d, J = 11.9 Hz, 1 H), 4.56 (d, J = 11.9 Hz, 1 H), 6.67 (t, J = 5.8 Hz, 1 H), 7.23-7.32 (m, 5 H).

¹³C NMR (100 MHz, CDCl3): δ = 13.8, 18.9, 19.1, 19.5, 27.2, 28.1, 68.2, 73.2, 81.3, 127.3, 127.5, 128.1, 137.9, 139.9.

HRMS: m/z [M + H]+ calcd for C16H26NO2: 264.1958; found: 264.1968.

Anal. Calcd for C16H25NO2: C, 72.96; H, 9.57; N, 5.32. Found: C, 73.02; H, 10.13; N, 5.48.

(S,Z)-1-(Benzyloxy)-3-methyl- N -(3-methylbutylidene)butan-2-amine Oxide (2o)

White solid; yield: 7.82 g (94%); mp 50-52 ˚C; R f  = 0.41 (hexane-EtOAc, 7:3).

[α]D ²5 -5 (c 1.13, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 0.90 (d, J = 6.6 Hz, 3 H), 0.92 (d, J = 6.6 Hz, 3 H), 0.93 (d, J = 6.7 Hz, 6 H), 1.89 (sept, J = 6.6 Hz, 1 H), 2.14 (m, 1 H), 2.39 (m, 2 H), 3.43 (ddd, J = 9.6, 9.3, 2.9 Hz, 1 H), 3.62 (dd, J = 9.9, 2.9 Hz, 1 H), 3.97 (dd, J = 9.9, 9.3 Hz, 1 H), 4.43 (d, J = 11.9 Hz, 1 H), 4.54 (d, J = 11.9 Hz, 1 H), 6.67 (t, J = 6.0 Hz, 1 H), 7.20-7.30 (m, 5 H).

¹³C NMR (100 MHz, CDCl3): δ = 19.1, 19.5, 22.4, 22.4, 25.8, 27.1, 35.0, 68.1, 73.1, 81.4, 127.3, 127.4, 128.1, 137.9, 139.1.

HRMS: m/z [M + H]+ calcd for C17H28NO2: 278.2115; found: 278.2121.

Anal. Calcd for C17H27NO2: C, 73.61; H, 9.81; N, 5.05. Found: C, 73.51; H, 9.98; N, 5.38.

(S,Z)-1-(Benzyloxy)- N -(2,2-dimethylpropylidene)-3-methyl­butan-2-amine Oxide (2p)

Oil; yield: 7.32 g (88%); R f  = 0.41 (hexane-EtOAc, 7:3).

[α]D ²5 -2 (c 1.08, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 0.95 (d, J = 6.6 Hz, 6 H), 1.30 (s, 9 H), 2.13 (ddt, J = 13.4, 9.8, 6.7 Hz, 1 H), 3.40 (dt, J = 9.5, 2.9 Hz, 1 H), 3.66 (dd, J = 10.2, 2.9 Hz, 1 H), 4.01 (dd, J = 10.2, 9.0 Hz, 1 H), 4.49 (d, J = 11.9 Hz, 1 H), 4.60 (d, J = 11.9 Hz, 1 H), 6.50 (s, 1 H), 7.27-7.35 (m, 5 H).

¹³C NMR (100 MHz, CDCl3): δ = 19.3, 19.4, 19.3, 26.0, 27.3, 32.8, 73.3, 82.1, 127.4, 127.5, 128.2, 138.1, 145.7.

HRMS: m/z [M + H]+ calcd for C17H28NO2: 278.2115; found: 278.2104.

Anal. Calcd for C17H27NO2: C, 73.61; H, 9.81; N, 5.05. Found: C, 73.88; H, 9.64; N, 5.24.

(S,Z)-1-(Benzyloxy)-3-methyl- N -pentylidenebutan-2-amine Oxide (2q)

White solid; yield: 6.82 g (82%); R f  = 0.23 (hexane-EtOAc, 7:3); mp 76-78 ˚C.

[α]D ²5 -2 (c 1.08, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 0.81-0.90 (m, 9 H), 1.30 (qt, J = 9.3, 6.2 Hz, 2 H), 1.40-1.49 (m, 2 H), 2.05-2.13 (m, 1 H), 2.45 (ddd, J = 7.4, 7.3, 5.9 Hz, 2 H), 3.37 (ddd, J = 9.4, 9.3, 3.0 Hz, 1 H), 3.58 (dd, J = 10.1, 3.0 Hz, 1 H), 3.94 (dd, J = 10.1, 9.3 Hz, 1 H), 4.39 (d, J = 11.9 Hz, 1 H), 4.51 (d, J = 11.9 Hz, 1 H), 6.61 (t, J = 5.9 Hz, 1 H), 7.21-7.23 (m, 5 H).

¹³C NMR (100 MHz, CDCl3): δ = 13.7, 19.2, 19.6, 22.5, 26.0, 27.3, 27.6, 68.2, 73.3, 127.5, 127.6, 128.2, 138.0, 141.0.

HRMS: m/z [M + H]+ calcd for C17H28NO2: 278.2115; found: 278.2107.

Anal. Calcd for C17H27NO2: C, 73.61; H, 9.81; N, 5.05. Found: C, 9.72; H, 9.68; N, 5.28.

(S,Z)-1-(Benzyloxy)-3-methyl- N -(2-phenylethylidene)butan-2-amine Oxide (2r)

Oil; yield: 8.03 g (86%); R f  = 0.26 (hexane-EtOAc, 7:3).

[α]D ²5 -15 (c 0.97, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 0.97 (d, J = 3.4 Hz, 3 H), 0.99 (d, J = 3.6 Hz, 3 H), 2.18-2.28 (m, 1 H), 3.52 (dt, J = 9.4, 3.0 Hz, 1 H), 3.70 (dd, J = 10.1, 3.0 Hz, 1 H), 3.81-3.88 (m, 1 H), 3.92-3.99 (m, 1 H), 4.07 (dd, J = 10.1, 9.4 Hz, 1 H), 4.50 (d, J = 11.8 Hz, 1 H), 4.60 (d, J = 11.8 Hz, 1 H), 6.88 (t, J = 5.7 Hz, 1 H), 7.21-7.40 (m, 10 H).

¹³C NMR (100 MHz, CDCl3): δ = 19.2, 19.6, 27.4, 32.9, 68.3, 73.3, 81.5, 126.7, 127.5, 127.6, 128.3, 128.6, 128.5, 136.5, 138.0, 138.5, 145.5.

HRMS: m/z [M + H]+ calcd for C20H26NO2: 312.1958; found: 312.1963.

Anal. Calcd for C20H25NO2: C, 77.14; H, 8.09; N, 4.502. Found: C, 77.29; H, 8.22; N,.37.

(S,Z)-1-(Benzyloxy)-3-methyl- N -(3-phenylpropylidene)butan-2-amine Oxide (2s)

Oil; yield: 8.69 g (89%); R f  = 0.20 (hexane-EtOAc, 1:1).

[α]D ²5 -3 (c 1.00, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 0.92 (d, J = 6.6 Hz, 3 H), 0.97 (d, J = 6.9 Hz, 3 H), 2.14-2.24 (m, 3 H), 2.87-2.94 (m, 2 H), 3.47 (dt, J = 9.3, 2.9 Hz, 1 H), 3.69 (dd, J = 10.1, 2.9 Hz, 1 H), 4.05 (dd, J = 10.1, 9.3 Hz, 1 H), 4.50 (d, J = 11.9 Hz, 1 H), 4.61 (d, J = 11.9 Hz, 1 H), 6.73 (t, J = 5.3 Hz, 1 H), 7.20-7.40 (m, 10 H).

¹³C NMR (100 MHz, CDCl3): δ = 19.2, 19.5, 27.3, 27.5, 31.2, 68.3, 73.2, 81.4, 126.1, 127.4, 127.5, 128.2, 128.3, 128.4, 137.9, 138.9, 140.5.

HRMS: m/z [M + H]+ calcd for C21H28NO2: 326.2115; found: 326.2107.

Anal. Calcd for C21H27NO2: C, 77.50; H, 8.36; N, 4.30. Found: C, 77.68; H, 8.27; N, 4.45.

(S,Z)-1-(Benzyloxy)- N -[2-(benzyloxy)ethylidene]-3-methyl­butan-2-amine Oxide (2t)

Oil; yield: 7.99 g (78%); R f  = 0.20 (hexane-EtOAc, 1:1).

[α]D ²5 +5 (c 1.08, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 0.94 (d, J = 2.4 Hz, 3 H), 0.96 (d, J = 2.7 Hz, 3 H), 2.09-2.21 (m, 1 H), 3.50 (ddd, J = 9.4, 9.3, 2.8 Hz, 1 H), 3.66 (dd, J = 10.1, 2.8 Hz, 1 H), 3.97 (dd, J = 10.1, 9.3 Hz, 1 H), 4.49-4.61 (m, 6 H), 6.94 (dd, J = 4.3, 4.3 Hz, 1 H), 7.23-7.40 (m, 10 H).

¹³C NMR (100 MHz, CDCl3): δ = 19.3, 19.7, 27.5, 65.7, 68.1, 73.4, 73.6, 81.3, 127.6, 127.7, 127.9, 127.9, 128.4, 128.5, 137.4, 137.9, 138.3.

HRMS: m/z [M + H]+ calcd for C21H28NO3: 342.2064; found: 342.2056.

Anal. Calcd for C21H27NO3: C, 73.87; H, 7.97; N, 4.10. Found: C, 73.76; H, 7.82; N, 4.00.

(S,Z)-1-(Benzyloxy)- N -[2-( tert -butoxycarbonylamino)ethylidene)]-3-methylbutan-2-amine Oxide (2u)

Oil; yield: 7.89 g (75%); R f  = 0.16 (hexane-EtOAc, 1:1).

[α]D ²5 +15 (c 0.96, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 0.85 (d, J = 6.6 Hz, 3 H), 0.88 (d, J = 6.8 Hz, 3 H), 1.35 (s, 9 H), 2.00-2.10 (m, 1 H), 3.42 (ddd, J = 9.4, 9.3, 3.0 Hz, 1 H), 3.57 (dd, J = 10.2, 3.0 Hz, 1 H), 3.89 (dd, J = 9.9, 9.4 Hz, 1 H), 3.95-4.01 (m, 2 H), 4.40 (d, J = 12.0 Hz, 1 H), 4.50 (d, J = 12.0 Hz, 1 H), 5.48 (br s, 1 H), 6.85 (t, J = 5.3 Hz, 1 H), 7.23-7.27 (m, 5 H).

¹³C NMR (100 MHz, CDCl3): δ = 19.2, 19.4, 27.6, 28.3, 68.0, 73.3, 81.2, 127.4, 127.6, 128.4, 136.3, 137.9.

HRMS: m/z [M + H]+ calcd for C19H31N2O: 351.2278; found: 351.2243.

Anal. Calcd for C19H30N2O4: C, 65.12; H, 8.63; N, 7.99. Found: C, 65.01; H, 8.48; N, 8.25.

(R,Z)-2-(Benzyloxy)- N -ethylidene-1-phenylethanamine Oxide (2v)

Oil; yield: 6.95 g (86%); R f  = 0.12 (hexane-EtOAc, 1:1).

[α]D ²5 -4 (c 0.90, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 1.95 (d, J = 5.8 Hz, 3 H), 3.68 (dd, J = 10.1, 3.8 Hz, 1 H), 4.41 (dd, J = 10.1, 9.3 Hz, 1 H), 4.46 (d, J = 12.0 Hz, 1 H), 4.60 (d, J = 12.0 Hz, 1 H), 4.88 (dd, J = 3.7, 9.3 Hz, 1 H), 6.86 (q, J = 5.8 Hz, 1 H), 7.12-7.30 (m, 10 H).

¹³C NMR (100 MHz, CDCl3): δ = 12.3, 19.1, 19.5, 27.3, 68.1, 73.2, 81.2, 127.4, 127.4, 128.2, 134.9, 137.9.

HRMS: m/z [M + H]+ calcd for C19H20NO2: 270.1492; found: 270.1486.

Anal. Calcd for C19H19NO2: C, 75.81; H, 7.11; N, 5.20. Found: C, 75.69; H, 7.26; N, 5.48.

(R,Z)-2-(Benzyloxy)- N -(2-methylpropylidene)-1-phenylethan­amine Oxide (2w)

Oil; yield: 8.48 g (95%); R f  = 0.15 (hexane-EtOAc, 4:1).

[α]D ²5 +17 (c 1.00, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 1.06 (d, J = 6.9 Hz, 3 H), 1.14 (d, J = 6.9 Hz, 3 H), 3.20 (d, sept, J = 7.9, 6.9 Hz, 1 H), 3.76 (dd, J = 10.2, 3.7 Hz, 1 H), 4.48 (dd, J = 10.2, 9.2 Hz, 1 H), 4.55 (d, J = 11.9 Hz, 1 H), 4.68 (d, J = 11.9 Hz, 1 H), 4.92 (dd, J = 9.2, 3.7 Hz, 1 H), 6.70 (d, J = 7.2 Hz, 1 H), 7.28-7.34 (m, 8 H), 7.46-7.50 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 18.8, 18.9, 25.9, 69.6, 73.5, 77.8, 127.6, 127.6, 127.8, 128.3, 128.5, 128.8, 134.7, 137.8, 145.3.

HRMS: m/z [M + Na]+ calcd for C19H24NO2: 298.1802; found: 298.1797.

Anal. Calcd for C19H23NO2: C, 76.73; H, 7.80; N, 4.71. Found: C, 76.80; H, 7.95; N, 4.59.

(R,Z)-2-(Benzyloxy)- N -(2,2-dimethylpropylidene)-1-phenyl­ethanamine Oxide (2x)

Oil; yield: 8.41 g (90%); R f  = 0.19 (hexane-EtOAc, 4:1).

[α]D ²5 -2 (c 0.98, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 1.28 (s, 9 H), 3.75 (dd, J = 9.8, 3.6 Hz, 1 H), 4.48 (dd, J = 9.8, 9.6 Hz, 1 H), 4.56 (d, J = 11.9 Hz, 1 H), 4.69 (d, J = 11.9 Hz, 1 H), 4.93 (dd, J = 9.6, 3.6 Hz, 1 H), 6.66 (s, 1 H), 7.27-7.38 (m, 8 H), 7.44-7.49 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 26.0, 32.8, 69.9, 73.5, 78.6, 127.5, 127.6, 128.3, 128.5, 128.6, 128.6, 135.1, 138.0, 145.3.

HRMS: m/z [M + H]+ calcd for C20H26NO: 312.1953; found: 312.1963.

Anal. Calcd for C20H25NO2: C, 77.14; H, 8.09; N, 4.50. Found: C, 77.03; H, 8.26; N, 4.47.

(R,Z)-2-(Benzyloxy)- N -[2-(benzyloxy)ethylidene]-1-phenyl­ethanamine Oxide (2y)

Oil; yield: 9.80 g (87%); R f  = 0.14 (hexane-EtOAc, 4:1).

[α]D ²5 -2 (c 1.13, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 3.76 (dd, J = 10.3, 3.8 Hz, 1 H), 4.41-4.58 (m, 6 H), 4.67 (d, J = 12.0 Hz, 1 H), 4.98 (dd, J = 9.1, 3.8 Hz, 1 H), 7.06 (t, J = 4.4 Hz, 1 H), 7.27-7.39 (m, 13 H), 7.44-7.50 (m, 2 H).

¹³C NMR (100 MHz, CDCl3): δ = 65.9, 69.3, 73.5, 73.6, 77.6, 127.7, 127.8, 128.9, 128.4, 128.1, 128.7, 129.1, 137.3, 137.5, 137.7.

Anal. Calcd for C24H25NO3: C, 76.77; H, 6.71; N, 3.73. Found: C, 76.89; H, 6.53; N, 3.95.

HRMS: m/z [M + Na]+ calcd for C24H25NaNO3: 398.1727; found: 398.1726.

(R,Z)-2-(Benzyloxy)- N -[2-( tert -butoxycarbonylamino)ethylidene]-1-phenylethanamine Oxide (2z)

Oil; yield: 9.46 g (82%); R f  = 0.16 (hexane-EtOAc, 1:1).

[α]D ²5 +15 (c 0.96, CHCl3).

¹H NMR (400 MHz, CDCl3): δ = 1.35 (s, 9 H), 3.42 (ddd, J = 9.4, 9.3, 3.0 Hz, 1 H), 3.57 (dd, J = 10.2, 3.0 Hz, 1 H), 3.89 (dd, J = 9.9, 9.4 Hz, 1 H), 3.95-4.01 (m, 2 H), 4.40 (d, J = 12.0 Hz, 1 H), 4.50 (d, J = 12.0 Hz, 1 H), 5.48 (br s, 1 H), 6.85 (t, J = 5.3 Hz, 1 H), 7.24-7.30 (m, 10 H).

¹³C NMR (100 MHz, CDCl3): δ = 19.2, 19.4, 27.6, 28.3, 68.0, 73.3, 81.2, 127.4, 127.6, 128.4, 136.3, 137.9.

HRMS: m/z [M + H]+ calcd for C22H29N2O4: 385.2116; found: 385.2106.

Anal. Calcd for C22H28N2O4: C, 68.73; H, 7.34; N, 7.29. Found: C, 68.96; H, 7.59; N, 7.14.

Acknowledgment

We thank for their support of our programs the Spanish Ministry of Science and Education (Madrid, Spain. Project CTQ2007-67532-C02-01), the European Regional Development Fund and the Government of Aragon (Zaragoza, Spain. Project PM-036/2007 and Research Group E-10). A.D. thanks Government of Aragon (Zaragoza, Spain) for a pre-doctoral grant. Z.G. thanks OTRI-UZ for a post-doctoral contract.

18

The authors have deposited the atomic coordinates for these structures with the Cambridge Crystallographic Data Centre. Deposition numbers are as follows: 1a, CCDC 753240; 1c, CCDC 753241; 1d, CCDC 753242; 1f, CCDC 753243; 1h, CCDC 753244; 1i, CCDC 753245; 1j, CCDC 753246; 1k, CCDC 753247; 2a, CCDC 753248; 2b, CCDC 753249; 2d, CCDC 753250; 2f, CCDC 753251; 2g, CCDC 753252; 2j, CCDC 753253; 2n, CCDC 753254; 2q, CCDC 753255. The coordinates can be obtained on request from the Director, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK.

18

The authors have deposited the atomic coordinates for these structures with the Cambridge Crystallographic Data Centre. Deposition numbers are as follows: 1a, CCDC 753240; 1c, CCDC 753241; 1d, CCDC 753242; 1f, CCDC 753243; 1h, CCDC 753244; 1i, CCDC 753245; 1j, CCDC 753246; 1k, CCDC 753247; 2a, CCDC 753248; 2b, CCDC 753249; 2d, CCDC 753250; 2f, CCDC 753251; 2g, CCDC 753252; 2j, CCDC 753253; 2n, CCDC 753254; 2q, CCDC 753255. The coordinates can be obtained on request from the Director, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK.

   Permissions and Reprints All articles of this category

Scheme 1

Scheme 2

Figure 1

Scheme 3

Scheme 4

Scheme 5

Scheme 6

Scheme 7