C O MMU N I C A T I O N S
Table 2. Conjugate Addition of Dialkylzinc Reagents to 1a and
The practicality of this new catalytic route is demonstrated by (i)
the synthesis of 2e on gram scale by starting with 10 mmol of 1a,
resulting in yields ranging from 86 to 91%,19 and (ii) the few
a
1c
2
efficient steps that are needed to obtain the corresponding â -amino
compounds (Scheme 3), in particular, the aldehydes which are
usually obtained via consecutive reduction and oxidation of the
acids.14 Together with the rhodium-catalyzed asymmetric hydro-
genation of â-dehydroamino acids using phosphoramidite ligands
2
0
2
reported recently by our group, both kinds of â-amino acids (â -
3
and â -substituted) can be obtained using the same class of
monodentate phosphoramidite ligands.
Acknowledgment. This project was funded by the National
Research School Combination Catalysis (NRSCC).
Supporting Information Available: Experimental procedures and
spectral and analytical data for reaction products (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
a
Conditions: 1.0 mmol of 1a,1c, 1.2 equiv of R2Zn in 2 mL of toluene;
all reactions went to completion (18 h for entries 3,4; 3 h for all others).
Isolated yield. Determined by chiral GC.
b
c
Scheme 3. Synthesis of â -Amino Acid, Aldehyde, and Alcohola
2
References
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(
(
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2
6) Although nitroacrylates are obvious substrates for the synthesis of â -
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a
See Supporting Information.
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2
Zn 1,4-addition product (R)-2e11 with
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the excellent ee of 98%, as it contains a stereogenic center bearing
a methyl substituent, which is a prominent feature in many natural
products.12 A major advantage of this asymmetric synthesis is that
the obtained nitroalkanes can be easily converted into (protected)
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002, 67, 7244-7254.
2
â -amino aldehydes, alcohols, and acids (Scheme 3). Raney-nickel-
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1
466.
catalyzed reduction of nitroalkane 2e, followed by Boc-protection,
(
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2
gives amino-acetal 3 which was deprotected to give â -amino-
(
13) (a) Nazar e´ , M.; Waldmann, H. Chem.-Eur. J. 2001, 7, 3363-3376. (b)
aldehyde 4, a building block used in the total synthesis of
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cyclamenol A.1 Because of the intermediate oxidation state of
3a
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5 6 3
amino-acetal 3, oxidation under acidic conditions (H IO , 1% CrO )
2
gives in a single step the corresponding N-Boc-protected â -amino
acid 6, used in the total synthesis of cryptophycins.14
(15) (a) Crumpler, H. R.; Dent, C. E.; Harris, H.; Westall, R. G. Nature 1951,
1
67, 307-308. (b) Asen, S.; Thompson, J. F.; Morris, C. J.; Irreverre, F.
The corresponding free amino acid has been isolated from human
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urine and Iris tingitana.15 Furthermore, â-amino-alcohol 5, a starting
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Anada, M.; Kitagaki, S.; Hashimoto, S. Heterocycles 2000, 52, 875-
16
material in the synthesis of â-methyl carbapenem antibiotics, was
obtained by reduction of aldehyde 4. Independent ee determinations
of 3-6 confirmed that no racemization had occurred and all
products were isolated with 98% ee.
8
83.
(17) Guichard, G.; Abele, S.; Seebach, D. HelV. Chim. Acta 1998, 81, 187-
2
06.
(
18) Salamonczyk, G. M.; Han, K.; Guo, Z.; Sih, C. J. J. Org. Chem. 1996,
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19) The fact that 6 is a crystalline compound provides a way to enhance the
enantiopurity even further by crystallization.
(
To the best of our knowledge, this is the first example of a
catalytic enantioselective route to these versatile building blocks
and an important addition to existing routes, which make use of
(20) Pe n˜ a, D.; Minnaard, A. J.; De Vries, J. G.; Feringa, B. L. J. Am. Chem.
Soc. 2002, 124, 14552-14553.
the chiral pool,17 (enzymatic) resolution, or chiral auxiliaries.
18
11
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J. AM. CHEM. SOC.
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