Killing double bonds softly: the reduction of polymer-bound alkenes

Abstract

Alkenes can be reduced through “transfer hydrogenation” with dimethylamine-borane adduct and Wilkinson's catalyst. This reaction can also be carried out by solid-phase synthesis as a heterogeneous reaction. Furthermore, the behaviour of various functional groups under hydrogenation conditions was tested.

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Introduction

Boranes, especially amino-borane adducts, were long known as reducing agents for carbonyl compounds (aldehydes, ketones, carboxylic acids, esters, amides) as well as imines. Moreover, they find use in reductive aminations and in the reduction of a variety of functional groups such as highly polarized carbon–carbon double bonds, oximes, tosylhydrazones, indoles, iminium salts, enamines and nitriles.² In the presence of transition metal catalysts amino-borane adducts also reduce aryl perfluorosulfonates, alkenes, quinoline, epoxides, alkynes, halides, aryl triflates and aryl nitro compounds.^3,4N-Alloc deprotection, epoxide openings and cleavage of benzyl esters are also known.^4,5 Berke et al. also showed that transfer hydrogenation of activated olefins with an ammonia-borane adduct is possible without a catalyst.⁶

As far as solid phase methods are concerned, only a few protocols are available for the reduction of double bonds. Previous works on solid-phase hydrogenation point out that there are difficulties to adapt traditional heterogeneous catalysis due to poor kinetics. One approach to circumvent the kinetic problems is to apply homogeneous reagents (resin or catalysts).⁷ The most employed method is probably the diimide reduction with sulfonohydrazides.⁸ Other “hydrogen-free” reductions employ copper(I) hydride and titanocene reagents, respectively,⁹ or Grubbs' catalyst and triethylsilane.¹⁰

During our research on solid-phase polyamine synthesis, we observed a reduction of double bonds of immobilized substrates as a byproduct under certain hydroboration conditions (Scheme 1). The hydroboration reaction with only pinacolborane gave poor yields, so we tried to improve the conversion by adding Wilkinson's catalyst. In on-bead ¹³C NMR we could identify signals for both hydroborated and hydrogenated products (2 and 3).

Scheme 1 Initial observation of double bond reduction. (a) Pinacolborane (HBPin, 5.00 equiv.), Wilkinson's catalyst (0.10 equiv.), dry CH₂Cl₂, 15 h.

Since a comparable method is only known in solution phase and not for solid-phase, we wanted to optimize our conditions towards hydrogenation and establish a mild reduction protocol.

For solution phase, Manners et al. developed a method for late transition metal-catalyzed dehydrocoupling of amine-borane adducts and thereby observed hydrogenation of COD (1,5-cyclooctadiene) while using rhodium catalysts. Cyclohexene was hydrogenated under the same conditions (Scheme 2).¹

Scheme 2 General equation for the catalytic dehydrocoupling of dimethylamine-borane adduct and hydrogenation of cyclohexene according to Manners et al.¹

Herein, we now report a new method for reduction in solid-phase synthesis under mild conditions using dimethylamine-borane adduct and Wilkinson's catalyst (tris(triphenylphosphine)-rhodium(I) chloride). We immobilized a mono-protected diamine, which gave us ample opportunities to introduce different alkenes and other functional groups that we tested under these conditions via alkylation or acylation.

Results and discussion

Our testing system core was mono-nosyl protected diaminopropane 5 which was immobilized on 2-chlorotrityl chloride resin (4). In a substitution reaction the protected amine and N,N-diisopropylethylamine (DIPEA) were added to the resin 4. Through Fukuyama-alkylation with various allylic halides and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in N,N-dimethyl-formamide (DMF) we obtained the resin 6 (see Experimental part). After these alkylation reactions, the nosyl-protecting group was removed using 2-mercaptoethanol and DBU to give resin 8. Subsequently, the immobilized alkenes were hydrogenated using our method, which is highlighted in detail below, to yield resin 9. The product 10 was cleaved from the resin in a final step using trifluoroacetic acid (TFA, Scheme 3).

Scheme 3 Synthesis of the substituted diamines 10 on 2-chlorotrityl chloride resin (4). (a) N-(3-Aminopropyl)-2-nitrobenzenesulfonamide (3.00 equiv.), DIPEA (3.00 equiv.), dry CH₂Cl₂, 15 h; (b) alkyl halide (6.00 equiv.), DBU (6.00 equiv.), DMF, 15 h; (c) 2-mercaptoethanol (10.0 equiv.), DBU (5.00 equiv.), DMF, 2 h; (d) carboxylic acid (5.00 equiv.), HOBt (5.00 equiv.), DIC (5.00 equiv.), DMF, 15 h; (e) dimethylamine-borane adduct (5.00 equiv.), Wilkinson's catalyst (0.10 equiv.), dry CH₂Cl₂, 15 h; (f) 5% TFA in CH₂Cl₂, 15 h. All reactions were conducted at room temperature. For R, R′ see Table 1 and Table 2.

Immobilization of mono-nosyl protected diaminopropane on 2-chlorotrityl chloride resin (4), the following Fukuyama alkylation, nosyl deprotection and final cleavage from the resin were performed according to the established protocols from our group¹¹ and slightly adapted protocols, respectively.

The reaction that really interested us was the hydrogenation step, which is now discussed in detail. The resins 8a–e were subjected to slightly modified dehydrocoupling/hydrogenation conditions, compared to the ones Manners et al.¹ applied, using dimethylamine-borane adduct and Wilkinson's catalyst in dry dichloromethane at room temperature (Scheme 3). Under these conditions, no hydroboration was observed and even without the addition of Wilkinson's catalyst and under elevated temperature no hydroboration occurred. Possible hydroboration was ruled out since afterwards there was no reaction with hydrogen peroxide/sodium hydroxide.

However, we achieved hydrogenation of the carbon–carbon double bonds. Not only terminal double bonds (Entry 1), but also substituted and internal double bonds (Entries 2–4) as well as alkynes (8e, Entry 5) gave good results. For analysis and quantification, the resulting compounds had to be cleaved from the resin and purified by HPLC. After five steps (immobilization, alkylation, deprotection, reduction and cleavage) we obtained our desired compounds in 60–96% overall yield (Table 1). Although we did not quantify every single step—most steps were monitored by NMR—overall yields for our five-step procedure show that every reaction proceeds in good to very good yields, including the hydrogenation step. In addition, there was no olefin observed after the final step, so the conversion should be complete.

Table 1 Reduction of alkenes and alkynes. Residue numbers are assigned in Scheme 4

Entry	Starting resin	Product	R^1	R^2	R^3	Isol. yield^a/Average yield per step [%]
a Total yield over five steps.
1	8a	9a	H	H	H	73/94
2	8b	9b	H	CH3	H	77/95
3	8c	9c	H	Ph	H	60/90
4	8d	9d	–(CH2)3–		H	96/99
5	8e	9e	H	H	—	65/92

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Scheme 4 Hydrogenation of alkene and alkyne substrates.

As shown in Table 1, hindered as well as unhindered alkenes can be reduced with our method. The reduction of the alkyne 8e cleanly resulted in the formation of the alkane derivative 9e.

With these results in hand we wanted to investigate the scope of the reaction by testing different functionalized substrates in the same manner (Table 2). Substrates that were available as benzyl halides were conjugated as described above. For carboxylic acids the sequence needed to be adapted (Scheme 3). The only difference was that resin 5 was first deprotected with 2-mercaptoethanol and DBU to give resin 7 and afterwards acylated with a carboxylic acid, 1-hydroxybenzotriazole (HOBt) and N,N′-diisopropylcarbodiimide (DIC) to yield resin 8. After this step the syntheses were the same.

Table 2 Results of the reduction and subsequent cleavage from the resin (steps e and f in Scheme 3) of various tethered functionalities

Entry		Resin 9	Isol. yield of amine 10^a/Average yield per step [%]
a Total yield over five steps. b Total yield over six steps. c Traces of amine/alcohol were observed in ESI-MS. d Equivalents of reagents were doubled.
6			30/78
			24/75
7	^d		49/87
			51/87
8			47/86
9			62/91
10			56/89
11			66/92
12			74/94
13			62/91
14			66^b/93
15			38/83^c
16			89/98
17			95/99^c
18			47/86

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In our study we tested aldehydes (Entry 12), ketones (Entries 13 and 18), imines (Entry 14), arylesters (Entry 15) and -halides (Entry 16) as well as nitrile- (Entries 6, 7 and 17), nitro- (Entries 8 and 9), benzylether- (Entry 10) and benzyloxycarbonyl (Cbz)- protecting (Entry 11) groups. We found that benzylethers (Entry 10), halides (Entry 16), arylesters (Entry 15) and the Cbz-group (Entry 11) were stable under the reducing conditions and gave good overall yields for the unreduced product. However, after reduction of arylester (Entry 15), traces of the corresponding alcohol could be found by ESI-MS. Again, the overall yields were consulted for conclusions. All steps proceed in good to excellent yields and the reduction step does not lead to any serious degradation.

Aldehydes (Entry 12), ketones (Entry 13), imines (Entry 14) and nitro-compounds (Entries 8 and 9) were readily reduced to the corresponding products in good overall yields. Nitriles were only partially reduced. Still, the overall yields considering both products were very good (Entries 6 and 7). After receiving preliminary results that showed incomplete conversion for the nitriles (Entry 6), we tried again with double the equivalents of the reducing agent (Entry 7). Again, the conversion was not complete and we obtained a mixture of nitrile and amine, but the ratio was shifted towards the amine. Longer reaction times or repetition of the reduction step might lead to complete reduction in this case, too.

It is also noteworthy that amides were not reduced during the reaction. In Table 2 the results for the reduction are mapped including the yields that were obtained after cleavage of the amine 10 from the resin.

Entries 17 and 18 in Table 2 are showcases to demonstrate that ketones and nitrile react only slowly and were not reduced in the presence of an ortho-amine group: they reacted intramolecularly to form aminals or amidates, respectively.

In summary we showed that our method not only hydrogenates C–C double bonds, but also reduces some functional groups whereas other functional groups are stable under the used conditions.

Conclusion

In conclusion, we were able to establish a new protocol for the reduction of alkenes and alkynes on a solid-phase. Aldehydes, ketones, imines and nitro-groups are also reduced under these conditions. In our test halides, arylesters, benzylethers, amides and Cbz-groups were stable. Only nitriles were found to be partially instable with our method.

Experimental

Attachment of monoprotected diamine to the resin

Resin 5. 2.00 mmol of the 2-Cl-Trt-Cl resin (4) was swollen in 12 mL dry dichloromethane and treated with 6.00 mmol DIPEA and 6.00 mmol N-(3-aminopropyl)-2-nitrobenzenesulfonamide. The reaction vessel was closed and shaken for 15 h at room temperature. Afterwards, 3 mL methanol was added and the mixture was shaken for another 15 min. The solvents were removed and the resin was washed with CH₂Cl₂/MeOH/CH₂Cl₂/MeOH/CH₂Cl₂/MeOH/CH₂Cl₂ and again CH₂Cl₂ (3 ×). The resin was dried in vacuo overnight.

¹³C NMR (Gel) (100 MHz, CDCl₃): δ = 147.7 (C_Ar–NO₂), 133.3 (C_Ar), 132.5 (C_Ar), 130.7 (C_Ar), 127.6 (C_Ar), 125.1 (C_Ar), 42.3 (CH₂NH), 40.1 (CH₂NH), 30.5 (CH₂CH₂) ppm.

Fukuyama-alkylation

Resin 6a. 0.20 mmol of resin 5 was swollen in 6 mL DMF and treated with 1.20 mmol DBU and 1.20 mmol allyl bromide. The reaction vessel was closed and shaken for 15 h at room temperature. Afterwards, the solvents were removed and the resin was washed with DMF, CH₂Cl₂/MeOH/CH₂Cl₂/MeOH/CH₂Cl₂ and again CH₂Cl₂ (3 ×). The resin 6a was dried in vacuo overnight.

¹³C NMR (Gel) (100 MHz, CDCl₃): δ = 147.7 (C_Ar–NO₂), 133.3 (C_Ar), 132.7 (CH=CH₂), 131.5 (C_Ar), 130.6 (C_Ar), 127.6 (C_Ar), 124.0 (C_Ar), 119.1 (CH=CH₂), 49.8 (CH₂CH=CH₂), 45.1 (CH₂N), 41.7 (CH₂N), 29.1 (CH₂(CH₂)₂) ppm.

Resin 6b. Crotyl bromide was used instead of allyl bromide.

¹³C NMR (Gel) (75 MHz, CDCl₃): δ = 147.8 (C_Ar–NO₂), 136.6 (C=CHCH₃), 133.3 (C_Ar), 131.5 (C_Ar), 130.6 (C_Ar), 127.7 (C_Ar), 125.1 (C_Ar), 123.9 (C=CHCH₃), 49.1 (C=CHCH₂N), 44.7 (NHCH₂CH₂CH₂N), 41.7 (CH₂NH), 40.3 (CH₂NH), 28.5 (CH₂(CH₂)₂), 17.7 (trans-CH₃), 12.8 (cis-CH₃) ppm.

Resin 6c. Cinnamyl bromide was used instead of allyl bromide.

¹³C NMR (Gel) (75 MHz, CDCl₃): δ = 147.7 (C_Ar–NO₂), 134.2 (C_Ar), 133.4 (C_Ar), 131.5 (PhC=CH), 130.7 (C_Ar), 128.5 (C_Ar), 127.9 (C_Ar), 126.4 (PhC=CH), 124.0 (C_Ar), 49.4 (C=CHCH₂N), 45.2 (CH₂N), 40.2 (CH₂N), 29.3 (CH₂(CH₂)₂) ppm.

Resin 6d. 2-Cyclohexen-1-yl bromide was used instead of allyl bromide.

¹³C NMR (Gel) (75 MHz, CDCl₃): δ = 147.9 (C_Ar–NO₂), 133.8 (C_Ar), 133.2 (C_Ar), 132.1 (C_Ar), 131.4 (NCHCH=CH), 130.6 (C_Ar), 125.7 (C_Ar), 123.9 (NCHCH=CH), 42.9 (CH₂N), 40.5 (CH₂N), 32.8 (CH₂(CH₂)₂), 28.7 (NCHCH₂), 24.3 (CH=CHCH₂), 21.6 (CH=CHCH₂CH₂) ppm.

Resin 6e. Propargyl bromide was used instead of allyl bromide.

Nosyl-deprotection

Resin 8a. 0.20 mmol of the resin 6a was swollen in 6 mL DMF and treated with 1.00 mmol DBU and 2.00 mmol 2-mercaptoethanol. The reaction vessel was closed and shaken for 1 h at room temperature. Afterwards the solvents were removed and the resin was washed with DMF until the filtrate stayed colorless. The whole procedure was repeated with only 30 min of reaction time until the reaction mixture stayed colorless. Afterwards, the resin was washed with DMF, CH₂Cl₂/MeOH/CH₂Cl₂/MeOH/CH₂Cl₂ and again CH₂Cl₂ (3 ×). The resin 8a was dried in vacuo overnight.

¹³C NMR (Gel) (100 MHz, CDCl₃): δ = 136.9 (CH=CH₂), 115.6 (CH=CH₂), 47.6 (CH₂CH=CH₂), 42.7 (CH₂N), 40.3 (CH₂N), 31.1 (CH₂(CH₂)₂) ppm.

Resin 8b. ¹³C NMR (Gel) (100 MHz, CDCl₃): δ = 129.5 (trans-C=CHCH₃), 127.6 (cis-C=CHCH₃), 126.9 (trans-C=CHCH₃), 125.8 (cis-C=CHCH₃), 51.7 (C=CHCH₂N), 47.6 (NHCH₂CH₂CH₂N), 46.0 (CH₂NH), 42.7 (CH₂NH), 31.2 (CH₂(CH₂)₂), 17.7 (trans-CH₃), 13.0 (cis-CH₃) ppm.

Resin 8c. ¹³C NMR (Gel) (75 MHz, CDCl₃): δ = 137.0 (C_Ar), 131.0 (PhC=CH), 128.4 (C_Ar), 127.2 (C_Ar), 126.1 (PhC=CH), 124.0 (C_Ar), 51.9 (C=CHCH₂N), 47.7 (CH₂N), 42.8 (CH₂N), 31.2 (CH₂(CH₂)₂) ppm.

Resin 8d. ¹³C NMR (Gel) (75 MHz, CDCl₃): δ = 130.0 (NCHCH=CH), 128.5 (NCHCH=CH), 45.2 (CH₂N), 42.8 (CH₂N), 31.5 (CH₂(CH₂)₂), 29.5 (NCHCH₂), 25.2 (CH=CHCH₂), 20.2 (CH=CHCH₂CH₂) ppm.

Resin 8e. ¹³C NMR (Gel) (100 MHz, CDCl₃): δ = 82.2 (CCH), 71.3 (CCH), 46.9 (CH₂N), 42.7 (CH₂N), 38.0 (CH₂N), 30.8 (CH₂(CH₂)₂) ppm.

Reduction

Resin 9a. 1.00 mmol dimethylamine-borane adduct was dissolved in 3 mL dry dichloromethane and argon was bubbled through for 5 min. After the addition of 0.02 mmol Wilkinson's catalyst, the mixture was added to resin 8a, which had been previously swollen in 3 mL dry dichloromethane. The reaction vessel was closed and shaken for 15 h at room temperature. Afterwards, the solvent was removed and the resin was washed with CH₂Cl₂, MeOH (3 ×) and again CH₂Cl₂ (3 ×). The resin 9a was dried in vacuo overnight.

¹³C NMR (Gel) (100 MHz, CDCl₃): δ = 22.2 (CH₂), 11.7 (CH₃) ppm.

Resin 9b. ¹³C NMR (Gel) (100 MHz, CDCl₃): δ = 19.4 (CH₂), 14.0 (CH₃) ppm.

Resin 9c. ¹³C NMR (Gel) (75 MHz, CDCl₃): δ = 128.2 (C_Ar) ppm.

Resin 9d. ¹³C NMR (Gel) (75 MHz, CDCl₃): δ = 26.9 (CH₂), 24.9 (CH₂) ppm.

Resin 9e. ¹³C NMR (Gel) (100 MHz, CDCl₃): δ = 10.5 (CH₃) ppm.

Cleavage

N ¹-Propylpropane-1,3-diamine (1a). In a vial 0.20 mmol of resin 9a was treated with 5% TFA solution in dichloromethane. The reaction vessel was closed and shaken for 15 h at room temperature. Afterwards, the solvents were removed and the resin was washed with CH₂Cl₂, MeOH (2 ×), CH₂Cl₂/MeOH/CH₂Cl₂/MeOH/CH₂Cl₂/MeOH/CH₂Cl₂ and again CH₂Cl₂ (3 ×). The organic phases were combined and the solvent was removed under reduced pressure to yield the crude product 10a. After HPLC purification of the crude product, 17 mg (0.146 mmol; 73% overall yield) of a colorless oil was obtained.

¹H NMR (400 MHz, MeOH-d₄): δ = 3.11 (t, J = 7.8 Hz, 2 H, CH₂NH₂), 3.05 (t, J = 7.6 Hz, 2 H, CH₂NH), 2.98 (t, J = 7.8 Hz, 2 H, CH₂NH), 2.07 (tt, J = 7.8 Hz, J = 7.6 Hz, 2 H, CH₂CH₂CH₂), 1.72 (tq, J = 7.8 Hz, J = 7.4 Hz, 2 H, CH₂CH₃), 1.02 (t, J = 7.4 Hz, 3 H, CH₃) ppm. – ¹³C NMR (100 MHz, MeOH-d₄): δ = 50.7 (−, CH₂NH), 45.8 (−, CH₂NH), 37.9 (−, CH₂NH₂), 25.4 (−, CH₂CH₂CH₂), 20.7 (−, CH₂CH₃), 11.2 (+, CH₃) ppm. – MS (ESI): m/z: 117.1 [M⁺+H]. – MS (FAB): m/z: 117.1 [M⁺+H]. – HRMS (C₆H₁₆N₂): calc. 116.1313; found 116.1312. – IR (ATR): ṽ = 3039 (w), 2974 (w), 2809 (w), 2558 (w), 2246 (vw), 1665 (s), 1608 (m), 1531 (w), 1485 (m), 1428 (m), 1349 (vw), 1195 (s), 1177 (s), 1124 (vs), 1004 (w), 962 (vw), 834 (m), 796 (m), 771 (w), 722 (s), 600 (w), 519 (w), 442 (w), 414 (w) cm⁻¹.

N ¹-Butylpropane-1,3-diamine (10b). After HPLC purification of the crude product, 20 mg (0.154 mmol; 77% overall yield) of an almost colorless solid was obtained.

¹H NMR (400 MHz, MeOH-d₄): δ = 3.11 (t, J = 7.8 Hz, 2 H, CH₂NH₂), 3.08–2.99 (m, 4 H, CH₂NH), 2.07 (tt, J = 7.8 Hz, 2 H, CH₂CH₂CH₂), 1.67 (tt, J = 7.8 Hz, 2 H, CH₂CH₂CH₂), 1.43 (tq, J = 7.8 Hz, J = 7.3 Hz, 2 H, CH₂CH₃), 0.98 (t, J = 7.3 Hz, 3 H, CH₃) ppm. – ¹³C NMR (100 MHz, MeOH-d₄): δ = 48.9 (−, CH₂NH), 45.8 (−, CH₂NH), 37.9 (−, CH₂NH₂), 29.2 (−, CH₂CH₂CH₂), 25.4 (−, CH₂CH₂CH₂), 20.8 (−, CH₂CH₃), 13.9 (+, CH₃) ppm. – MS (ESI): m/z: 131.2 [M⁺+H].– MS (FAB): m/z: 131.1 [M⁺+H]. – HRMS (C₇H₁₈N₂): calc. 130.1470; found 130.1475. – IR (ATR): ṽ = 3038 (w), 2870 (w), 2230 (vw), 1665 (s), 1606 (m), 1531 (w), 1485 (m), 1429 (m), 1349 (vw), 1177 (s), 1124 (s), 969 (w), 920 (vw), 834 (m), 796 (m), 770 (w), 721 (s), 600 (w), 519 (w), 442 (w), 412 (w) cm⁻¹. – mp: 149.4 °C.

N ¹-(3-Phenylpropyl)propane-1,3-diamine (10c). After HPLC purification of the crude product, 23 mg (0.120 mmol; 60% overall yield) of a white solid was obtained.

¹H NMR (400 MHz, MeOH-d₄): δ = 7.32–7.17 (m, 5 H, H_Ar), 3.10 (t, J = 7.8 Hz, 2 H, CH₂NH₂), 3.07–2.99 (m, 4 H, CH₂NH), 2.72 (t, J = 7.8 Hz, 2 H, CH₂C_Ar), 2.06 (tt, J = 7.8 Hz, 2 H, CH₂CH₂CH₂), 2.01 (tt, J = 7.8 Hz, 2 H, CH₂CH₂CH₂) ppm. – ¹³C NMR (100 MHz, MeOH-d₄): δ = 141.6 (C_quart), 129.7 (+, 2 × CH_Ar), 129.4 (+,2 × CH_Ar), 127.5 (+, CH_Ar), 48.7 (−, CH₂NH), 45.8 (−, CH₂NH), 37.8 (−, CH₂NH₂), 33.5 (−, CH₂C_Ar), 29.0 (−, CH₂CH₂), 25.4 (−, CH₂CH₂) ppm. – MS (ESI): m/z: 193.2 [M⁺+H]. – MS (FAB): m/z: 193.2 [M⁺+H]. –HRMS (C₁₂H₂₁N₂): calc. 193.1705; found 193.1704. – IR (ATR): ṽ = 3028 (w), 2944 (w), 2797 (w), 2231 (vw), 1663 (s), 1536 (w), 1496 (w) 1484 (w), 1454 (w), 1429 (w), 1326 (vw), 1177 (s), 1130 (s), 906 (vw), 836 (m), 796 (m), 768 (w), 751 (m), 723 (s), 694 (m), 600 (w), 570 (w), 519 (w), 493 (w), 461 (w), 441 (w), 411 (w) cm⁻¹. – mp: 157.9 °C.

N ¹-Cyclohexylpropane-1,3-diamine (10d). After HPLC purification of the crude product, 30 mg (0.192 mmol; 96% overall yield) of an almost colorless solid was obtained.

¹H NMR (400 MHz, MeOH-d₄): δ = 3.21–3.02 (m, 5 H, CH₂NH₂, CH₂NH, CHNH), 2.16–2.02 (m, 4 H, CH₂CH₂N + 2 × cHexH), 1.93–1.85 (m, 2 H, cHexH), 1.75–1.68 (m, 1 H, cHexH), 1.43–1.32 (m, 4 H, cHexH), 1.29–1.16 (m, 1 H, cHexH) ppm. – ¹³C NMR (100 MHz, MeOH-d₄): δ = 58.7 (+, CHNH), 42.7 (−, CH₂NH), 37.9 (−, CH₂NH₂), 30.3 (−, NH₂CH₂CH₂), 26.1 (−, 2 × CHCH₂), 25.6 (−, CHCH₂CH₂CH₂), 25.5 (−, 2 × CHCH₂CH₂) ppm. – MS (ESI): m/z: 157.2 [M⁺+H]. – MS (FAB): m/z: 157.2 [M⁺+H]. – HRMS (C₉H₂₁N₂): calc. 157.1705; found 157.1704. – IR (ATR): ṽ = 3034 (m), 2934 (m), 2857 (m), 1665 (s), 1529 (w), 1500 (w), 1431 (m), 1394 (w), 1172 (s), 1120 (s), 1069 (m), 1053 (m), 1032 (w), 972 (vw), 942 (vw), 897 (vw), 838 (m), 797 (s), 765 (w), 721 (s), 674 (vw), 598 (w), 581 (vw), 517 (w), 447 (w), 414 (w) cm⁻¹. – mp: 153.7 °C.

N ¹-Propylpropane-1,3-diamine (10e). After HPLC purification of the crude product, 15 mg (0.129 mmol; 65% overall yield) of an almost colorless oil was obtained.

¹H NMR (400 MHz, MeOH-d₄): δ = 3.11 (t, J = 7.8 Hz, 2 H, CH₂NH₂), 3.05 (t, J = 7.6 Hz, 2 H, CH₂NH), 2.98 (t, J = 7.8 Hz, 2 H, CH₂NH), 2.07 (tt, J = 7.8 Hz, 2 H, CH₂CH₂CH₂), 1.72 (tq, J = 7.6 Hz, J = 7.4 Hz, 2 H, CH₂CH₃), 1.02 (t, J = 7.4 Hz, 3 H, CH₃) ppm. – ¹³C NMR (100 MHz, MeOH-d₄): δ = 50.7 (−, CH₂NH), 45.8 (−, CH₂NH), 37.9 (−, CH₂NH₂), 25.4 (−, CH₂CH₂CH₂), 20.7 (−, CH₂CH₃), 11.2 (+, CH₃) ppm. [Impurity: 2-mercaptoethanol <10%]. – MS (ESI): m/z: 117.1 [M⁺+H]. – MS (FAB): m/z: 117.1 [M⁺+H]. – HRMS (C₆H₁₆N₂): calc. 116.1313; found 116.1314. – IR (ATR): ṽ = 2794 (w), 1666 (s), 1475 (w), 1427 (w), 1193 (s), 1126 (s), 835 (m), 798 (m), 758 (w), 721 (m), 598 (w), 518 (w), 438 (w), 411 (w) cm⁻¹.

Acknowledgements

This work was supported by the Carl Zeiss Stiftung (fellowship for D. F.).

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Footnote

† Electronic Supplementary Information (ESI) available: Experimental details and NMR spectra. See DOI: 10.1039/c2ra22189f

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