References and Notes
For selected reviews on the use of 1,2-diacetals as chiral building blocks in organic synthesis, see:
1a
Ley SV.
Baeschlin DK.
Dixon DJ.
Foster AC.
Ince SJ.
Priepke HWM.
Reynolds DJ.
Chem. Rev.
2001,
101:
53
1b
Ley SV.
Baxendale IR.
Grice P.
NATO Science Series (II, Mathematics, Physics and Chemistry)
Vol. 129:
Schneider M.
Kluwer Academic Publishers;
Netherlands:
2003.
p.235
1c
Ley SV.
Polara A.
J. Org. Chem.
2007,
72:
5943
2
Ley SV.
Michel P.
Synthesis
2004,
147
Both enantiomers of glyceraldehyde acetonide are prone to racemization and rapid polymerization. See:
3a
Hubschwerlen J.
Specklin L.
Higelin J.
Org. Synth
1995,
72:
1
3b
Schmid CR.
Bryant JD.
Org. Synth.
1995,
72:
6
4
Annunziata R.
Benaglia M.
Cinquini M.
Cozzi F.
Raimondi L.
Tetrahedron
1994,
50:
5821
5
Annunziata R.
Benaglia M.
Cinquini M.
Cozzi F.
Ponzini F.
Bioorg. Med. Chem. Lett.
1993,
3:
2397
See for instance:
6a
Hubschwerlen C.
Schmid G.
Helv. Chim. Acta
1983,
66:
2206
6b
Bose AK.
Hedge VR.
Wagle DR.
Bari SS.
Manhas MS.
J. Chem. Soc., Chem. Commun.
1986,
161
6c
Thomas RC.
Tetrahedron Lett.
1989,
30:
5239
6d
Alcaide B.
Polanco C.
Sierra MA.
J. Org. Chem.
1998,
63:
6786
6e
Grigg R.
Thornton-Pett M.
Xu J.
Xu LH.
Tetrahedron
1999,
55:
13841
7
Jarayaman M.
Deshmukh ARAS.
Bhawal DM.
J. Org. Chem.
1994,
59:
932
8
Palomo C.
Oiarbide M.
Landa A.
Esnal A.
Linden A.
J. Org. Chem.
2001,
66:
4180
9
General Procedure: A stirred solution of the aldehyde 1 (0.842 mmol) in anhyd Et2O (1.6 mL) at 0 °C was treated with the corresponding amine (0.681 mmol) and molecular sieves (Merck 4 Å). After the reaction was complete, the molecular sieves were filtered and the solvent was evaporated under vacuum to yield the corresponding imine 3. Compound 3a: R = Bn; reaction time: 25 min, 0 °C, 98%. Compound 3b: R = (R)-CH(Me)(Ph); reaction time: 15 min, 0 °C, 99%. Compound 3c: R = (S)-CH(Me)(Ph); reaction time: 15 min, 0 °C, 81%.
10
General Procedure: A solution of the imine 3 (0.784 mmol) in CH2Cl2 (3.9 mL) was treated with Et3N (2.359 mmol) followed by the dropwise addition of a solution of the corresponding acyl chloride (1.196 mmol) in CH2Cl2 (2.6 mL) at 0 °C under an argon atmosphere. After the reaction was completed, the reaction mixture was poured into H2O (6.6 mL), stirred for 15 min, and then extracted with CH2Cl2 (3 × 6.6 mL). The combined organic layers were washed with 5% NaHCO3 (2 × 2.6 mL), dried with MgSO4 and concentrated in vacuum affording a mixture of the corresponding β-lactams 4. The major diastereoisomer was obtained by direct crystallization from the reaction mixture and purified by recrystallization from hexane-EtOAc. The minor isomer was isolated from the mother liquors by column chromatography (silica gel, hexane-EtOAc, 6:1) and further HPLC separation when it was necessary (semipreparative system, Zorbax RX-SIL column, hexane-EtOAc, 60:40; 3 mL/min). Compounds 4a,b: R = Bn, R1 = PhO; reaction time: 25 min, 0 °C, 91%. Compounds 4c,d: R = Bn, R1 = p-ClC6H4O; reaction time: 25 min, 0 °C, 72%. Compounds 4e,f: R = (R)-CH(Me)(Ph), R1 = PhO; reaction time: 15 min, r.t., 66%. Compounds 4g,h: R = (S)-CH(Me)(Ph), R1 = PhO; reaction time: 15 min, r.t., 61%.
11 Crystal structure analysis for 4a: mp 138-139 °C. C24H29NO6, Mr = 427.48 g mol-1. Crystallographic data (excluding structure factors) for compound 4a have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 661975. Crystal structure analysis for 4e: mp 136-137 °C. C25H31NO6, Mr = 441.51 g mol-1. Crystallographic data (excluding structure factors) for compound 4e have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 661977. Crystal structure analysis for 4g: mp 185-186 °C. C25H31NO6, Mr = 441.51 g mol-1. Crystallographic data (excluding structure factors) for compound 4g have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 661976.
12 A solution of the diastereomerically pure β-lactam 4e (0.165 mmol) in a mixture of TFA-H2O (9:1, 1.18 mL) was stirred at r.t. for 5 min. Then the reaction mixture was evaporated under vacuum and the resulting oil was purified by column chromatography (silica gel, hexane-EtOAc, 1:2), yielding 2a as a white solid (33 mg, 61%), which was recrystallized from hexane-CH2Cl2; [α]D -119.0, [α]578 -124.5, [α]546 -142.8, [α]436 -257.3, [α]546 -434.9 (c = 0.53, CH2Cl2, 25 °C). 1H NMR (400 MHz, CDCl3): δ = 7.45 (d, J = 7.2 Hz, 2 H, Ph), 7.39 (t, J = 7.2 Hz, 2 H, Ph), 7.27-7.33 (m, 3 H, Ph), 7.12 (d, J = 8.0 Hz, 2 H, Ph), 7.04 (t, J = 7.2 Hz, 1 H, Ph), 5.24 (d, J
3,4 = 5.2 Hz, 1 H, H-3), 4.82 (q, J
1
′′,Me = 7.2 Hz, 1 H, H-1′′), 3.96-4.01 (m, 1 H, H-1′), 3.88 (t, J
4,1
′ = J
4,3 = 5.2 Hz, 1 H, H-4), 3.66 (dd, J
2
′a,2
′b = 11.2 Hz, J
1
′,2
′a = 4.0 Hz, 1 H, H-2′a), 3.57 (dd, J
2
′b,1
′ = 6.4 Hz, J
2
′a,2
′b = 11.2 Hz, 1 H, H-2′b), 2.39 (1 H, OH), 1.78 (d, J
Me,1
′′ = 7.2 Hz, 3 H, Me). 13C NMR (100 MHz, CDCl3): δ = 166.1 (CO), 157.4 (Ph), 141.0 (Ph), 129.7, 128.9, 127.8, 127.0 (Ph), 122.7 (Ph), 115.9 (Ph), 79.5 (C-3), 71.2 (C-1′), 63.6 (C-2′), 59.5 (C-1′′), 54.7 (C-4), 20.3 (Me).
13
2b: [α]D -88.2, [α]578 -92.8, [α]546 -105.8, [α]436 -189.8, [α]546 -322.9 (c = 0.42, CH2Cl2, 25 °C). 1H NMR (400 MHz, CDCl3): δ = 7.26-7.38 (m, 7 H, Ph), 7.08 (d, J = 8.8 Hz, 2 H, Ph), 5.17 (d, J
3,4 = 5.2 Hz, 1 H, H-3), 4.81 (d, J
1
′′a,1
′′b = 14.8 Hz, 1 H, H-1′′a), 4.41 (d, J
1
′′a,1
′′b = 14.8 Hz, 1 H, H-1′′b), 4.09-4.13 (m, 1 H, H-1′), 3.84 (t, J
4,1
′ = J
4,3 = 5.2 Hz, 1 H, H-4), 3.74 (dd, J
2
′a,2
′b = 11.2 Hz, J
1
′,2
′a = 3.6 Hz, 1 H, H-2′a), 3.63 (dd, J
2
′a,2
′b = 11.2 Hz, J
1
′,2
′b = 6.4 Hz, 1 H, H-2′b). 13C NMR (100 MHz, CDCl3): δ = 165.9 (CO), 155.9 (Ph), 135.5 (Ph), 129.6, 129.0, 128.4, 127.9 (Ph), 117.3 (Ph), 80.6 (C-3), 71.3 (C-1′), 63.8 (C-2′), 57.9 (C-4), 45.9 (Me). 2c: [α]D +82.1, [α]578 +86.0, [α]546 +98.7, [α]436 +177.0, [α]546 +299.6 (c = 0.53, CH2Cl2, 25 °C). 1H NMR (400 MHz, CDCl3): δ = 7.27-7.40 (m, 7 H, Ph), 7.11 (d, J = 8.8 Hz, 2 H, Ph), 5.25 (d, J
3,4 = 5.2 Hz, 1 H, H-3), 4.77 (d, J
1
′′a,1
′′b = 14.8 Hz, 1 H, H-1′′a), 4.22 (d, J
1
′′a,1
′′b = 14.8 Hz, 1 H, H-1′′b), 4.05-4.09 (m, 1 H, H-1′), 3.92 (t, J
4,1
′ = J
4,3 = 5.2 Hz, 1 H, H-4), 3.81 (dd, J
2
′a,1
′ = 3.1 Hz, J
2
′a,2
′b = 11.6 Hz, 1 H, H-2′a), 3.65 (dd, J
2
′b,1
′ = 6.4 Hz, J
2
′a,2
′b = 11.6 Hz, 1 H, H-2′b). 13C NMR (100 MHz, CDCl3): δ = 165.8 (CO), 155.6 (Ph), 134.9 (Ph), 129.6, 129.0, 128.3, 128.2 (Ph), 117.4 (Ph), 81.4 (C-3), 70.8 (C-1′), 63.9 (C-2′), 57.4 (C-4), 45.5 (C-1′′).