UPDATES
The product 5a was obtained as a solid (30 mg, 51%). The
NMR spectra of this product agreed with those reported in the
literature.[18] 1H NMR (CDCl3, 400 MHz): δ=3.60 (s, 2H) 1.23
(s, 6H). 13C NMR (CDCl3, 101 MHz): δ=182.9, 69.5, 44.2
22.1 ppm.
(lit.:[10j] [α]20D =À 4.8 (c 4.0, CHCl3) (R)). The NMR spectra of
this product were indistinguishable from those of (R)-5g.
(R)-2-(Hydroxymethyl)butanoic acid ((R)-5g). The title com-
pound was prepared using wild-type KPHMT following the
procedure described for (R)-5g (substrates: 1g (59 mg,
0.5 mmol), formaldehyde (563 μL of a 13.4 M stock solution,
7.5 mmol)). The product (R)-5g was obtained as an oil (12 mg,
40%), 97% ee. The ee was determined by HPLC analysis on
(R)-6g derivative (CHIRALPAK® ID 4.6×250 mm column,
(S)-3-Hydroxy-2-methylpropanoic acid ((S)-5d). The title
compound was prepared using MBP-YfaU W23V following the
procedure described for (S)-5d (substrates: 1d (52 mg,
0.5 mmol), formaldehyde (563 μL of a 13.4 M stock solution,
7.5 mmol)). The product (S)-5d was obtained as an oil (30 mg,
53%), 98% ee. The ee was determined by HPLC analysis on
(S)-6d derivative (CHIRALCEL® ID 4.6×250 mm column,
5 μm, flow rate 0.7 mLminÀ 1 at 20 C and UV detection
°
(254 nm), isocratic elution hexane:iPrOH 75:25; tR (S)=
13.8 min; tR (R)=15.8 min). [α]20D =À 5.0 (c 0.7, CHCl3)
(lit.:[10j] [α]20D =À 4.8 (c 4.0, CHCl3) (R)). The NMR spectra of
this product agreed with those reported in the literature.[20]
NMR of S-5g and R-5g: 1H NMR (CDCl3, 400 MHz): δ=
3.82–3.80 (2H, m), 2.60–2.53 (1H, m), 1.78–1.60 (2H, m),
1.00 (t, J=7.5 Hz, 3H) ppm. 13C NMR (CDCl3, 101 MHz): δ=
179.7, 62.7, 48.7, 21.6, 11.8.
5 μm, flow rate 0.7 mLminÀ 1 at 20 C and UV detection
°
(254 nm), isocratic elution hexane:iPrOH 75:25; tR (S)=
15.7 min; tR (R)=17.0 min). [α]20D = +11.7 (c 1.2, EtOH)
(lit.:[19] [α]20D =À 11.6 (c 1.0, EtOH) (R)). The NMR spectra of
this product were indistinguishable from those of (R)-5d.
(R)-3-Hydroxy-2-methylpropanoic acid ((R)-5d). The title
compound was prepared using KPHMT I212A following the
procedure described for (R)-5d (substrates: 1d (52 mg,
0.5 mmol), formaldehyde (563 μL of a 13.4 M stock solution,
7.5 mmol)). The product (R)-5d was obtained as an oil (11 mg,
22%), 98% ee. The ee was determined by HPLC analysis on
(S)-6d derivative (CHIRALCEL® ID 4.6×250 mm column,
(S)-2-(Hydroxymethyl)pentanoic acid ((S)-5h). The title
compound was prepared using MBP-YfaU W23V following the
procedure described for (S)-5h (substrates: 1h (66 mg,
0.5 mmol), formaldehyde (563 μL of a 13.4 M stock solution,
7.5 mmol)). The product (S)-5h was obtained as an oil (52 mg,
79%), 97% ee. The ee was determined by HPLC analysis on
(S)-6h derivative (CHIRALPAK® ID 4.6×250 mm column,
5 μm, flow rate 0.7 mLminÀ 1 at 20 C and UV detection
°
5 μm, flow rate 0.7 mLminÀ 1 at 20 C and UV detection
°
(254 nm), isocratic elution hexane:iPrOH 75:25; tR (S)=
15.7 min; tR (R)=17.0 min). [α]20D =À 11.0 (c 0.5, EtOH)
(lit.:[19] [α]20D =À 11.6 (c 1.0, EtOH) (R)). The NMR spectra of
this product agreed with those reported in the literature.[19]
(254 nm), isocratic elution hexane:iPrOH 75:25; tR (S)=
12.7 min; tR (R)=14.4 min). [α]20D = +3.1 (c 1.1, CHCl3)
(lit.:[10j] [α]20D =À 3.0 (c 10, CHCl3) (R)). The NMR spectra of
this product were indistinguishable from those of (R)-5h.
1
NMR of S-5d and R-5d: H NMR (400 MHz, CDCl3) δ=3.75
(d, J=6.0 Hz, 2H), 2.75 À 2.68 (m, 1H), 1.21 (d, J=7.3 Hz,
3H) ppm. 13C NMR (101 MHz, CDCl3): δ=180.7, 64.5, 41.6,
13.3 ppm.
(R)-2-(Hydroxymethyl)pentanoic acid ((R)-5h). The title
compound was prepared using KPHMT I212A following the
procedure described for (R)-5h (substrates: 1h (66 mg,
0.5 mmol), formaldehyde (563 μL of a 13.4 M stock solution,
7.5 mmol)). The product (R)-5h was obtained as an oil (25 mg,
38%), 92% ee. The ee was determined by HPLC analysis on
(R)-6h derivative (CHIRALPAK® ID 4.6×250 mm column,
(S)-2-(Hydroxymethyl)-2-methylbutanoic acid ((S)-5e). The
title compound was prepared using KPHMT I212A following
the procedure described for (S)-5e (substrates: 1e (66 mg,
0.5 mmol), formaldehyde (563 μL of a 13.4 M stock solution,
7.5 mmol)). The product (S)-5e was obtained as an oil (49 mg,
45%), 98% ee. The ee was determined by HPLC analysis on
(S)-6e derivative (CHIRALPAK® ID 4.6×250 mm column,
5 μm, flow rate 0.7 mLminÀ 1 at 20 C and UV detection
°
(254 nm), isocratic elution hexane:iPrOH 75:25; tR (S)=
12.7 min; tR (R)=14.4 min). [α]20D =À 4.2 (c 0.7, CHCl3)
(lit.:[10j] [α]20D =À 3.0 (c 10, CHCl3)(R)). The NMR spectra of
this product agreed with those reported in the literature.[9b]
5 μm, flow rate 0.7 mLminÀ 1 at 20 C and UV detection
°
(254 nm), isocratic elution hexane:iPrOH 75:25; tR (S)=
45.8 min; tR (R)=48.4 min). [α]20D = +4.0 (c 0.7, CHCl3)
(lit.:[10j] [α]20D =À 4.8 (c 4.0, CHCl3) (R)). The NMR spectra of
this product agreed with those reported in the literature.[10j] 1H
NMR (CDCl3, 400 MHz): δ=3.76–3.73 (m, 1H), 3.55–3.52 (m,
1H), 1.72–1.58 (m, 2 H), 1.2 (s, 3H), 0.92 (t, J=7.5 Hz, 3H)
ppm. 13C NMR (CDCl3, 101 MHz): δ=182.7, 67.8, 48.0, 28.5,
19.0, 8.7 ppm.
1
NMR of S-5h and R-5h: H NMR (CDCl3, 400 MHz): δ=δ
3.80–3.73 (m, 2H), 2.67–2.60 (m, 1H), 1.70–1.65 (m, 1H),
1.58–1.49 (m, 1H), 1.44–1.38 (m, 2H), 0.94 (t, J=7.3 Hz,
3H).13C NMR (CDCl3, 101 MHz): δ=180.4, 63.9, 47.4, 30.5,
20.5, 14.1.
(S)-2-Benzyl-3-hydroxypropanoic acid ((S)-5i). The title
compound was prepared using MBP-YfaU W23V following the
procedure described for (S)-5i (substrates: 1i (90 mg,
0.5 mmol), formaldehyde (563 μL of a 13.4 M stock solution,
7.5 mmol)). The product (S)-5i was obtained as a solid (56 mg,
62%), 95% ee. The ee was determined by HPLC analysis on
(S)-6i derivative (CHIRALPAK® ID 4.6×250 mm column,
(S)-2-(Hydroxymethyl)butanoic acid ((S)-5g). The title com-
pound was prepared using MBP-YfaU W23V following the
procedure described for (S)-5g (substrates: 1g (59 mg,
0.5 mmol), formaldehyde (563 μL of a 13.4 M stock solution,
7.5 mmol)). The product (S)-5g was obtained as an oil (21 mg,
70%), 96% ee. The ee was determined by HPLC analysis on
(S)-6g derivative (CHIRALPAK® ID 4.6×250 mm column,
5 μm, flow rate 0.7 mLminÀ 1 at 20 C and UV detection
°
(254 nm), isocratic elution hexane:iPrOH 75:25; tR (S)=
26.3 min; tR (R)=25.5 min). [α]20D =À 10.4 (c 1.5, CHCl3)
(lit.:[10j] [α]20D = +12.5 (c 2.0, CHCl3) (R)). The NMR spectra
of this product were indistinguishable from those of (R)-5i.
5 μm, flow rate 0.7 mLminÀ 1 at 20 C and UV detection
°
(254 nm), isocratic elution hexane:iPrOH 75:25; tR (S)=
13.8 min; tR (R)=15.8 min). [α]20D = +3.5 (c 0.8, CHCl3)
Adv. Synth. Catal. 2021, 363, 1–12
9
© 2021 The Authors. Advanced Synthesis & Catalysis
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