Application of the ester enolate Claisen rearrangement in the synthesis of amino acids containing quaternary carbon centers

Article abstract of DOI:10.1021/jo960014g

Ester enolate Claisen rearrangement of highly substituted amino acid allylic esters 4 allows for the synthesis of sterically demanding amino acids 5 with β-quaternary carbon centers. Because of enolate fixation by chelation, the rearrangement occurs in a highly diastereoselective fashion. The methodology is suitable not only for glycine derivatives but also for allylic esters of various amino acids. In this case amino acids with two vicinal quaternary carbon centers are created. With unsymmetrically substituted allylic esters like 4k-n the rearrangement proceeds with a high degree of diastereoselectivity.

Full text of DOI:10.1021/jo960014g

3694
J . Org. Chem. 1996, 61, 3694-3699
Ap p lica tion of th e Ester En ola te Cla isen Rea r r a n gem en t in th e
Syn th esis of Am in o Acid s Con ta in in g Qu a ter n a r y Ca r bon Cen ter s
Uli Kazmaier
Organisch-Chemisches Institut der Universita¨t, Im Neuenheimer Feld 270,
D-69120 Heidelberg, Federal Republic of Germany
Received J anuary 2, 1996X
Ester enolate Claisen rearrangement of highly substituted amino acid allylic esters 4 allows for
the synthesis of sterically demanding amino acids 5 with â-quaternary carbon centers. Because of
enolate fixation by chelation, the rearrangement occurs in a highly diastereoselective fashion. The
methodology is suitable not only for glycine derivatives but also for allylic esters of various amino
acids. In this case amino acids with two vicinal quaternary carbon centers are created. With
unsymmetrically substituted allylic esters like 4k -n the rearrangement proceeds with a high degree
of diastereoselectivity.
In tr od u ction
issue and is therefore not yet well developed. Besides
Michael- and cycloadditions, the sigmatropic rearrange-
ment processes are suitable for this purpose.11 The major
procedures applied to amino acid syntheses are the
rearrangement of amino acid allylic esters via oxazole-
intermediates,12 developed by Steglich,13 and the Ireland-
Claisen rearrangement,14,15 investigated by Bartlett.16
In a previous communication we described a new
variation of the ester enolate Claisen rearrangement, one
that is especially suitable for R-amino acid synthesis.17
Deprotonation of N-protected amino acid allylic esters
Amino acids containing quaternary â-carbon centers
are, in addition to R-alkylated amino acids, an especially
interesting class of nonproteinogenic amino acids. The
most common representative, tert-leucine, occurs as a
building block in various complex natural products like
bottromycin A,1 milnamide A,2 the related hemiasterlins3
or the discodermins.4 Recently, tert-leucine was used as
a precursor for the synthesis of chiral auxiliaries5 and
ligands6 applied to asymmetric synthesis. While various
methods are known for the synthesis of R-alkylated
amino acids,7 there are fewer procedures available for the
formation of amino acids containing quaternary â-cen-
ters.8 During the last years numerous investigations
have been undertaken into the synthesis of tert-leucine9
and its derivatives.10 But the stereoselective generation
of amino acids with chiral â-carbon centers is not a trivial
(9) For recent synthesis of tert-leucine see: (a) Mu¨nster, P.; Steglich,
W. Synthesis 1987, 223. (b) Yamada, T.; Motoyama, N.; Taniguchi, T.;
Kazuta, Y.; Miyazawa, T.; Kuwata, S.; Matsumoto, K.; Sugiura, M.
Chem. Lett. 1987, 723. (c) Kunz; H.; Pfrengle, W.; Sager, W. Tetrahe-
dron Lett. 1989, 30, 4109. (d) Evans, D. A.; Britton, T. C.; Ellman, J .
A.; Dorow, R. L. J . Am. Chem. Soc. 1990, 112, 4011. (e) Kunz, H.;
Pfrengle, W.; Ru¨ck, K.; Sager, W. Synthesis 1991, 1039. (f) Corey, E.
J .; Link, J . O. J . Am. Chem. Soc. 1992, 114, 1906. (g) Obrecht, D.;
Spiegler, C.; Scho¨nholzer, P.; Mu¨ller, K.; Heimgartner, H.; Stierli, F.
Helv. Chim. Acta 1992, 75, 1666. (h) Inaba, T.; Kozono, I.; Fujita, M.;
Ogura, K. Bull. Chem. Soc. J pn. 1992, 65, 2359. (i) Durst, T.; Koh, K.
Tetrahedron Lett. 1992, 33, 6799. (k) Clive, D. L. J .; Etkin, N.
Tetrahedron Lett. 1994, 35, 2459.
X Abstract published in Advance ACS Abstracts, May 1, 1996.
(1) Schipper, D. J . Antibiot. 1983, 36, 1076.
(2) Crews, P.; Farias, J . J .; Emrich, R.; Keifer, P. A. J . Org. Chem.
1994, 59, 2932.
(3) Coleman, J . E.; de Silva, E. D.; Kong, F.; Andersen, R. J .; Allen,
T. M. Tetrahedron 1995, 51, 10653.
(4) (a) Matsunage, S.; Fusetani, N.; Konosu, S. Tetrahedron Lett.
1984, 25, 5165. (b) Matsunage, S.; Fusetani, N.; Konosu, S. Tetrahedron
Lett. 1985, 26, 855.
(10) (a) Scho¨llkopf, U.; Ku¨hnle, W.; Egert, E.; Dyrbusch, M. Angew.
Chem. 1987, 99, 480; Angew. Chem., Int. Ed. Engl. 1987, 28, 480. (b)
Bretschneider, T.; Miltz, W.; Mu¨nster, P.; Steglich, W. Tetrahedron
1988, 44, 5403. (c) Murakami, M.; Hasegawa, N.; Tomita, I.; Inouye,
M.; Ito, Y. Tetrahedron Lett. 1989, 30, 1257. (d) Mooiweer, H. H.;
Ettema, K. W. A.; Hiemstra, H.; Speckamp, W. N. Tetrahedron 1990,
46, 2991. (e) Easton, C. J .; Scharfbillig, I. M. J . Org. Chem. 1990, 55,
384. (f) Barker, J .; Cook, S. L.; Lasterra-Sa´nchez, M. E.; Thomas, S.
E. J . Chem. Soc., Chem. Commun. 1992, 830. (g) Groth, U.; Huhn,
T.; Porsch, B.; Schmeck, C.; Scho¨llkopf, U. Liebigs Ann. Chem. 1993,
715. (h) Boeykens, M.; De Kimpe, N.; Abbaspour T. K. J . Org. Chem.
1994, 59, 6973. (i) Yamamoto, Y.; Kubota, Y.; Honda, Y.; Fukui, H.;
Asao, N.; Nemoto, H. J . Am. Chem. Soc. 1994, 116, 3161. (k) Freskos,
J . N. Synth. Commun. 1994, 24, 557. (l) Barker, J .; Cook, S. L.;
Lasterra-Sa´nchez, M. E.; Thomas, S. E. Inorg. Chim. Acta 1994, 220,
137.
(11) (a) Takano, S.; Akiyama, M.; Ogasawara, K. J . Chem. Soc.,
Chem. Commun. 1984, 770. (b) Ito, Y.; Higuchi, N.; Murakami, M.
Tetrahedron Lett. 1988, 5151.
(12) (a) Burger, K.; Geith, K.; Gaa, K. Angew. Chem. 1988, 100, 860;
Angew. Chem., Int. Ed. Engl. 1988, 27, 848. (b) Castelhano, A. L.;
Horne, S.; Taylor, G. J .; Billedeau, R.; Krantz, A. Tetrahedron 1988,
44, 5451. (c) Colombo, L.; Casiraghi, G.; Pittalis, A.; Rassu, G. J . Org.
Chem. 1991, 56, 3897. (d) Holladay, M. W.; Nadzan, A. M. J . Org.
Chem. 1991, 56, 3900.
(5) (a) Hashimoto, S.; Yamada, S.; Koga, K. J . Am. Chem. Soc. 1976,
98, 7450. (b) Tomioka, K.; Masumi, F.; Yamashita, T.; Koga, K.
Tetrahedron Lett. 1984, 25, 333. (c) Whittaker, M.; McArthur, C. R.;
Leznoff, C. C. Can. J . Chem. 1985, 63, 2844. (d) Evans, D. A.;
Chapman, K. T.; Hung, D. T.; Kawaguchi, A. T. Angew. Chem. 1987,
99, 1197; Angew. Chem., Int. Ed. Engl. 1987, 26, 1184. (e) Tomioka,
K.; Masumi, F.; Yamashita, T.; Koga, K. Tetrahedron 1989, 45, 643.
(f) Paquette, L. A.; Macdonald, D.; Anderson, L. G. J . Am. Chem. Soc.
1990, 112, 9292. (g) Meyers, A. I.; Shipman, M. J . Org. Chem. 1991,
56, 7098. (h) Snider, B. B.; Yang, K. J . Org. Chem. 1992, 57, 3615.
(6) (a) Hayashi, T.; Fukushima, M.; Konishi, M.; Kumada, M.
Tetrahedron Lett. 1980, 21, 79. (b) Hayashi, T., Konishi, M.; Fuku-
shima, M.; Kanehira, K.; Hioki, T.; Kumada, M. J . Org. Chem. 1983,
48, 2195. (c) Brunner, H.; Obermann, U. Chem. Ber. 1989, 122, 499.
(d) Nishiyama, H.; Sakaguchi, H.; Nakamura, T.; Horihata, M.; Kondo,
M.; Itoh, K. Organometallics 1989, 8, 846. (e) Lowenthal, R. E.; Abiko,
A.; Masamune, S. Tetrahedron Lett. 1990, 31, 6005. (f) Nishiyama, H.;
Kondo, M.; Nakamura, T.; Itoh, K. Organometallics 1991, 10, 500. (g)
Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul, M. M. J . Am. Chem.
Soc. 1991, 113, 726. (h) Mu¨ller, D.; Umbricht, G.; Weber, B.; Pfaltz, A.
Helv. Chim. Acta 1991, 74, 232. (i) Leutenegger, U.; Umbricht, G.;
Fahrni, C.; von Matt, P.; Pfaltz, A. Tetrahedron 1992, 48, 2143. (k)
Evans, D. A.; Faul, M. M.; Bilodeau, M. T.; Anderson, B. A.; Barnes,
D. M. J . Am. Chem. Soc. 1993, 115, 5328.
(13) (a) Ku¨bel, B.; Ho¨fle, G.; Steglich, W. Angew. Chem. 1975, 87,
64. Angew. Chem., Int. Ed. Engl. 1975, 14, 58. (b) Engel, N.; Ku¨bel,
B.; Steglich, W. Angew. Chem. 1977, 89, 408; Angew. Chem., Int. Ed.
Engl. 1977, 16, 394.
(7) (a) Williams, R. M. Synthesis of Optically Active R-Amino Acids;
Vol. 7 of Organic Chemistry Series; Baldwin, J . E., Magnus, P. D., Eds.;
Pergamon Press: Oxford, 1989.
(8) For reviews on asymmetric syntheses of quaternary carbon
centers see: (a) Martin, S. F. Tetrahedron 1980, 36, 419. (b) Fuji, K.
Chem. Rev. 1993, 93, 2037.
(14) Ireland, R. E.; Mueller, R. H.; Willard, A. K. J . Am. Chem. Soc.
1976, 98, 2868.
(15) Baumann, H.; Duthaler, R. O. Helv. Chim. Acta 1988, 71, 1025.
(16) (a) Bartlett, P. A.; Tanzella, D. J .; Barstow, J . F. Tetrahedron
Lett. 1982, 619. (b) Bartlett, P. A.; Barstow, J . F. J . Org. Chem. 1982,
47, 3933.
S0022-3263(96)00014-X CCC: $12.00 © 1996 American Chemical Society

Quaternary Carbon-Containing Amino Acids
J . Org. Chem., Vol. 61, No. 11, 1996 3695
Sch em e 1
Various metal salts can be used for chelation (Table 1,
entries 1-4), but in general best results are obtained with
zinc chloride and methylaluminum dichloride. Therefore
zinc chloride was applied for this purpose in standard
reactions because it is less expensive and easier to
handle. The rearrangement can be applied to acyclic as
well as to cyclic substrates (entries 5-8). That this
methodology is not limited to glycine esters is illustrated
with the rearrangement of various amino acid allylic
esters (entries 9-15). Aliphatic as well as aromatic side
chains are suitable, and the extremely sterically demand-
ing R-alkylated amino acids21 are obtained in good yields.
The influence of the protecting group Y was investigated
for the phenylalanine derivative (entries 11-14), and no
significant dependence on the protecting group is ob-
served for the rearrangement. This makes the method
of general value for the synthesis of various N-protected
amino acids and peptides.
Sch em e 2
In addition to the equally substituted allylic esters (R1
) R2) the unsymmetrically substituted esters (R1 * R2)
are especially interesting substrates. Their rearrange-
ment allows the diastereoselective generation of chiral
â-quaternary carbon centers (Table 2).
The rearrangement of the E-configured esters (entries
15-17) resulted in the formation of the syn-configured
amino acid in a highly diastereoselective fashion. The
observed diastereoselectivity (g95% ds) is in good agree-
ment with the selectivities observed for other E-config-
ured allylic esters,17 and results from a preferential
rearrangement via a chairlike transition state.22 On the
other hand, the rearrangement of the Z-configured neryl
ester 4n (entry 18) gave rise to the opposite diastereomer,
although with a significantly lower degree of selectivity.
The lower diastereoselectivity may result from interac-
tions of the cis-oriented side chain and the chelated
enolate. These interactions should destabilize the chair-
like transitions state with the consequence that the
boatlike transition state should become more favored.
To prove this possibility, the acetylenic substrates 4o
and 4p were also subjected to rearrangement (Scheme
3).23 Because of the acidic acetylenic proton, 3.5 equiv
of LDA were used for the rearrangement of these
substrates. While the E-configured ester 4o gave the
expected product 5o in a highly diastereoselective fash-
ion, the oppositely configured Z-ester 4p unexpectedly
yields the same product, although less selectively.
(Scheme 1) such as 1 with LDA at -78 °C and subsequent
addition of a metal salt (MXn) presumably results in the
formation of a chelated metal enolate 2, which undergoes
Claisen rearrangement upon warming to room temper-
ature, giving rise to unsaturated amino acid 3.
In contrast to the corresponding lithium enolates,
which do not show this rearrangement, due to decompo-
sition during warming, the chelate enolates are much
more stable. Otherwise, the metal enolates are clearly
superior to silylketene acetals, both in terms of their
reactivity and selectivity.16 The driving force for the
accelerated rearrangement of the chelate enolates is
probably the transformation of the high-energy ester
enolate 2 into a chelate bridged, stabilized carboxylate
3. Due to the fixed enolate geometry, as a result of
chelate formation, the rearrangement proceeds with a
high degree of diastereoselectivity, independent of the
substitution pattern and the protecting groups Y used.
This method is suitable for acyclic as well as cyclic allylic
esters18 and can also be applied to peptides.19
In this article our investigations into the stereoselective
synthesis of sterically demanding amino acids using this
chelate enolate Claisen rearrangement are presented.20
The formation of the same product from these comple-
mentary precursors can be explained by a change of the
transition state geometry (Scheme 4).
Resu lts a n d Discu ssion
The E-configured ester 4o rearranges preferentially via
the expected chairlike transition state A. In the case of
the Z-configured ester 4p strong steric interactions could
arise in the corresponding transition state C between the
triple bond and the presumably solvated chelated metal.
The system can switch to the boatlike transition state D
to avoid these possible interactions, accepting the less
dramatic interaction of the axial hydrogen and the
chelate. This has the consequence that the syn product
5o is also produced preferentially.
Because of the promising results obtained with E-
configured glycine allylic esters, the chelate ester enolate
rearrangement was also applied to the rearrangement
of highly substituted allylic esters like 4 (Scheme 2),
giving rise to amino acids containing quaternary â-carbon
centers. Starting from amino acids other than glycine
(R1 * H) allows for the generation of two vicinal quater-
nary centers in one step.
The influence of the protecting group Y, the substitu-
tion pattern, as well as the metal salt MXn, used for
chelation of the ester enolate, were investigated. The
results are listed in Table 1.
(21) Kazmaier, U.; Maier, S. J . Chem. Soc., Chem. Commun. 1995,
1991.
(22) Wipf, P. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds., Pergamon Press, Oxford, 1991; Vol. 5, p 827, and
cited literature.
(23) It should be noted that the ester 4o and should be prepared
directly before use or should be stored at -50 °C to avoid decomposi-
tion.
(17) Kazmaier, U. Angew. Chem. 1994, 106, 1096. Angew. Chem.,
Int. Ed. Engl. 1994, 33, 998.
(18) Kazmaier, U. Tetrahedron 1994, 50, 12895.
(19) Kazmaier, U. J . Org. Chem. 1994, 59, 6667.
(20) Kazmaier, U. Synlett 1995, 1138.

3696 J . Org. Chem., Vol. 61, No. 11, 1996
Ta ble 1. Ester En ola te Cla isen Rea r r a n gem en t of Am in o Acid Allylic Ester s 4
Kazmaier
yielda
entry
substrate
Y
R1
R2
R3
R4
MXn
ZnCl2
product
1
2
4a
4a
4a
4a
4b
4b
4c
4c
4d
4e
4f
Cbz
Cbz
Cbz
Cbz
Boc
Boc
Boc
Boc
Boc
Cbz
Boc
TFA
Ts
H
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
H
H
H
H
H
H
H
H
H
H
H
H
H
H
5a
5a
5a
5a
5b
5b
5c
5c
5d
5e
5f
81%
78%
75%
36%
64%
62%
45%
69%
68%
69%
64%
67%
75%
69%
H
H
H
H
H
H
H
CH3
Bn
Bn
Bn
Bn
Ph
AlMeCl2
MgCl2
Al(OiPr)3
ZnCl2
AlMeCl2
ZnCl2
AlMeCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
ZnCl2
3
4
5
6
7
8
9
-(CH2)4-
-(CH2)4-
-(CH2)5-
-(CH2)5-
CH3
CH3
CH3
CH3
CH3
CH3
CH3
10
11
12
13
14
CH3
CH3
CH3
CH3
CH3
4g
4h
4i
5g
5h
5i
TFA
a
Isolated yield after esterification with diazomethane.
Ta ble 2. Ester En ola te Cla isen Rea r r a n gem en t of Un sym m etr ica l Su bstitu ted Am in o Acid Allylic Ester s 4 in th e
P r esen ce of Zin c(II) Ch lor id e
entry
substrate
Y
R1
R2
R3
R4
product
% yielda
% ds
15
16
17
18
4k
4l
4m
4n
Boc
TFA
Boc
Boc
H
CH3
H
CtC-pTol
Ph
(CH2)2CHdC(CH3)2
CH3
CH3
CH3
CH3
H
CH3
H
5k
5l
5m
5n
65
62
46
43
96b
96b
95c
73c
H
(CH2)2CHdC(CH3)2
H
Isolated yield after esterification with diazomethane. Determined by HPLC. c Determined by NMR.
a
b
Sch em e 3
Sch em e 4
Introduction of bulky substituents (aryl or trialkylsilyl
groups) on the acetylenic moiety has no further influence
on the reaction, e.g. rearrangement of the Z-configured
analogue of ester 4k also proceeded preferentially via the
boatlike transition state. Yield and diastereoselectivity
were comparable to the results obtained with the basic
ester 4p .
Con clu sion
In conclusion it has been shown, that the ester enolate
Claisen rearrangement of amino acid allylic esters is a
suitable method for the synthesis of sterically demanding
amino acids with even two vicinal quaternary carbon
centers. Because of the fixation of the enolate geometry
by chelation, the rearrangement proceeds in a highly
diastereoselective fashion. Further investigations, par-
ticularly into the asymmetric synthesis of quaternary
amino acids by rearrangement of chiral allylic esters and
rearrangements in the presence of chiral ligands,24 are
in progress.
Exp er im en ta l Section
Gen er a l P r oced u r e. General procedures and methods for
characterization have been described previously.19 1H and 13C
NMR spectra were recorded in CDCl3 on a Bruker AC-300
(24) Kazmaier, U.; Krebs, A. Angew. Chem. 1995, 107, 2213. Angew.
Chem., Int. Ed. Engl. 1995, 34, 2012.

Quaternary Carbon-Containing Amino Acids
J . Org. Chem., Vol. 61, No. 11, 1996 3697
spectrometer. Chemical shifts were reported in δ relative to
CHCl3 as an internal reference. Melting points were deter-
mined on a Tottoli melting point apparatus and are uncor-
rected.
P r ep a r a tion of th e Am in o Acid Allylic Ester s. The
allylic ester derivatives 4 used as substrates were synthesized
by coupling of N-protected amino acids and the corresponding
allylic alcohol using dicyclohexylcarbodiimide and 4-(dimethy-
lamino)pyridine.25
3-Met h yl-2-b u t en yl N-(Ben zyloxyca r b on yl)glycin a t e
(4a ). 4a was obtained from N-(benzyloxycarbonyl)glycine and
3-methyl-2-butenol in 86% yield (after flash chromatography,
ethyl acetate/hexanes 3/7) as a colorless oil: 1H NMR δ 7.35
(m, 5H), 5.35 (tbr, 1H), 5.29 (tq, J ) 6.0, 1.4 Hz, 1H), 5.13 (s,
2H), 4.64 (d, J ) 7.4 Hz, 2H), 3.96 (d, J ) 5.6 Hz, 2H), 1.73 (s,
3H), 1.68 (s, 3H); 13C NMR δ 170.2, 156.2, 140.6, 136.2, 128.5,
128.2, 128.1, 117.5, 66.9, 62.8, 42.8, 25.6, 17.87. Anal. Calcd
for C15H19NO4: C, 64.97; H, 6.91; N, 5.05. Found: C, 65.04;
H, 6.86; N, 5.01.
(2-Cyclop en tylid en eeth yl) N-(ter t-Bu tyloxyca r bon yl)-
glycin a te (4b). 4b was obtained from N-(tert-butyloxycar-
bonyl)glycine and 2-cyclopentylideneethanol in 76% yield (after
flash chromatography, ethyl acetate/hexanes 2/8) as a colorless
oil: 1H NMR δ 5.40 (tt, J ) 7.2, 2.3 Hz, 1H), 5.04 (sbr, 1H),
4.60 (d, J ) 7.2 Hz, 2H), 3.88 (d, J ) 5.8 Hz, 2H), 2.26 (m,
4H), 1.68 (m, 4H), 1.42 (s, 9H); 13C NMR δ 170.3, 155.6, 151.4,
113.5, 79.9, 63.6, 42.7, 33.8, 28.8, 26.1, 25.9. Anal. Calcd for
C14H23NO4: C, 62.43; H, 8.61; N, 5.20. Found: C, 62.60; H,
8.66; N, 5.11.
(2-Cycloh exylid en eeth yl) N-(ter t-Bu tyloxyca r bon yl)-
glycin a te (4c). 4c was obtained from N-(tert-butyloxycarbo-
nyl)glycine and 2-cyclohexylideneethanol in 73% yield (after
flash chromatography, ethyl acetate/hexanes 2/8) as a colorless
oil: 1H NMR δ 5.25 (t, J ) 7.3 Hz, 1H), 5.06 (tbr, 1H), 4.63 (d,
J ) 7.3 Hz, 2H), 3.87 (d, J ) 5.4 Hz, 2H), 2.17 (m, 2H), 2.09
(m, 2H), 1.53 (m, 6H), 1.42 (s, 9H); 13C NMR δ 170.3, 155.6,
147.6, 114.6, 79.9, 61.4, 42.5, 37.0, 29.0, 28.3, 27.7, 26.5. Anal.
Calcd for C15H25NO4: C, 63.58; H, 8.89; N, 4.94. Found: C,
63.23; H, 8.74; N, 4.86.
3-Met h yl-2-b u t en yl N-(ter t-Bu t yloxyca r b on yl)a la n i-
n a te (4d ). 4d was obtained from N-(tert-butyloxycarbonyl)-
alanine and 3-methyl-2-butenol in 93% yield (after flash
chromatography, ethyl acetate/hexanes 2/8) as a colorless oil:
1H NMR δ 5.31 (tq, J ) 7.2, 1.4 Hz, 1H), 5.06 (dbr, 1H), 4.69
(d, J ) 7.2 Hz, 2H), 4.27 (m, 1H), 1.73 (s, 3H), 1.68 (s, 3H),
1.42 (s, 9H), 1.35 (d, J ) 7.1 Hz, 3H); 13C NMR δ 173.3, 155.1,
139.5, 118.2, 79.7, 62.1, 49.3, 28.3, 25.7, 18.7, 18.0. Anal. Calcd
for C13H23NO4: C, 60.68; H, 9.01; N, 5.44. Found: C, 60.82;
H, 8.92; N, 5.55.
3-Meth yl-2-bu ten yl N-(Ben zyloxyca r bon yl)p h en yla la -
n in a te (4e). 4e was obtained from N-(benzyloxycarbonyl)-
phenylalanine and 3-methyl-2-butenol in 68% yield (after flash
chromatography, ethyl acetate/hexanes 2/8) as a colorless oil:
1H NMR δ 7.34 (s, 5H), 7.24 (m, 3H), 7.10 (dd, J ) 7.0, 1.6 Hz,
2H), 5.27 (m, 2H), 5.10 (s, 2H), 4.61 (m, 3H), 3.12 (m, 2H),
1.77 (s, 3H), 1.70 (s, 3H); 13C NMR δ 171.4, 155.6, 139.9, 136.4,
135.8, 129.4, 128.5, 128.1, 128.0, 127.0, 118.1, 66.9, 62.3, 54.9,
38.3, 25.7, 18.0. Anal. Calcd for C22H25NO4: C, 71.91; H, 6.86;
N, 3.81. Found: C, 72.11; H, 6.67; N, 3.84.
3-Meth yl-2-bu ten yl N-(ter t-Bu tyloxyca r bon yl)p h en y-
la la n in a te (4f). 4f was obtained from N-(tert-butyloxycar-
bonyl)phenylalanine and 3-methyl-2-butenol in 84% yield
(after flash chromatography, ethyl acetate/hexanes 2/8) as a
colorless oil: 1H NMR δ 7.24 (m, 3H), 7.12 (dd, J ) 6.3, 1.4
Hz, 2H), 5.29 (tt, J ) 7.3, 1.4 Hz, 1H), 4.93 (dbr, J ) 7.4 Hz,
1H), 4.59 (m, 3H), 3.06 (m, 2H), 1.76 (s, 3H), 1.69 (s, 3H), 1.41
(s, 9H); 13C NMR δ 171.8, 155.1, 139.6, 136.1, 129.4, 128.4,
126.9, 118.2, 62.1, 54.5, 38.4, 28.3, 25.7, 18.0. Anal. Calcd
for C19H27NO4: C, 68.44; H, 8.16; N, 4.20. Found: C, 68.17;
H, 8.11; N, 4.27.
chromatography, ethyl acetate/hexanes 2/8) as a white solid:
mp 35-36 °C: 1H NMR δ 7.27 (m, 3H), 7.08 (m, 2H), 6.83 (sbr,
1H), 5.33 (td, J ) 7.4, 1.2 Hz, 1H), 4.85 (q, J ) 6.6 Hz, 1H),
4.70 (dd, J ) 12.0, 7.4 Hz, 1H), 4.65 (dd, J ) 12.0, 7.4 Hz,
1H), 3.24 (dd, J ) 14.0, 5.7 Hz, 1H), 3.16 (dd, J ) 14.0, 5.4
Hz, 1H), 1.79 (s, 3H), 1.73 (s, 3H); 13C NMR δ 169.2, 156.5 (q,
J ) 37.5 Hz), 140.7, 134.7, 129.3, 128.7, 127.5, 117.5, 115.7,
(q, J ) 287.6 Hz), 62.9, 53.6, 37.2, 25.7, 18.0. Anal. Calcd for
C16H18NO3F3: C, 58.36; H, 5.51; N, 4.15. Found: C, 58.32; H,
5.66; N, 4.17.
3-Met h yl-2-b u t en yl N-(p -Tolylsu lfon yl)p h en yla la n i-
n a te (4h ). 4h was obtained from N-(p-tolylsulfonyl)phenyla-
lanine and 3-methyl-2-butenol in 79% yield (after flash chro-
matography, ethyl acetate/hexanes 2/8) as a colorless oil: 1H
NMR δ 7.46 (d, J ) 8.3 Hz, 2H), 7.23 (m, 5H), 7.08 (m, 2H),
5.09 (m, 2H), 4.35 (d, J ) 7.3 Hz, 2H), 4.18 (dt, J ) 9.0, 6.0
Hz, 1H), 3.02 (d, J ) 6.0 Hz, 2H), 2.39 (s, 3H), 1.73 (s, 3H),
1.61 (s, 3H); 13C NMR δ 170.7, 143.4, 140.7, 139.5, 135.0, 129.5,
128.4, 127.2, 127.1, 117.6, 62.4, 56.6, 39.5, 25.6, 21.5, 17.9.
Anal. Calcd for C21H25NO4S: C, 65.09; H, 6.50; N, 3.61.
Found: C, 64.88; H, 6.46; N, 3.66.
3-Met h yl-2-b u t en yl N-(Tr iflu or oa cet yl)p h en ylglyci-
n a t e (4i). 4i was obtained from N-(trifluoroacetyl)phenyl-
glycine and 3-methyl-2-butenol in 86% yield (after flash
chromatography, ethyl acetate/hexanes 2/8) as a white solid:
mp 80-81 °C: 1H NMR δ 7.36 (s, 6H), 5.55 (d, J ) 7.1 Hz,
1H), 5.26 (t, J ) 7.3 Hz, 1H), 4.71 (dd, J ) 12.1, 7.3 Hz, 1H),
4.59 (dd, J ) 12.1, 7.3 Hz, 1H), 1.72 (s, 3H), 1.63 (s, 3H); 13C
NMR δ 169.5, 156.3 (q, J ) 38.00 Hz), 140.8, 134.9, 129.1,
129.0, 127.2, 117.3, 115.6 (q, J ) 287.7 Hz), 63.4, 56.6, 25.6,
17.9. Anal. Calcd for C15H16NO3F3: C, 57.14; H, 5.11; N, 4.44.
Found: C, 57.27; H, 5.31; N, 4.39.
(E)-3-Meth yl-5-(4-m eth ylph en yl)pen t-2-en -4-yn yl N-(ter t-
Bu tyloxyca r bon yl)glycin a te (4k ). 4k was obtained from
N-(tert-butyloxycarbonyl)glycine and (E)-3-methyl-5-(4-meth-
ylphenyl)pent-2-en-4-ynol26 in 93% yield (after flash chroma-
tography, ethyl acetate/hexanes 3/7) as a pale yellow oil: 1H
NMR δ 7.31 (d, J ) 8.0 Hz, 2H), 7.10 (d, J ) 8.0 Hz, 2H), 5.97
(td, J ) 7.3, 1.4 Hz, 1H), 5.05 (tbr, 1H), 4.75 (d, J ) 7.3 Hz,
2H), 3.91 (d, J ) 5.4 Hz, 2H), 2.33 (s, 3H), 1.95 (d, J ) 1.5 Hz,
3H), 1.44 (s, 9H); 13C NMR δ 170.1, 155.7, 138.4, 131.5, 129.1,
128.8, 124.2, 120.0, 90.3, 88.9, 80.0, 61.3, 42.5, 28.3, 21.4, 17.8.
Anal. Calcd for C20H25NO4: C, 69.95; H, 7.34; N, 4.08.
Found: C, 69.88; H, 7.25; N, 3.97.
(E)-2-Meth yl-3-p h en yl-2-bu ten yl N-(Tr iflu or oa cetyl)-
a la n in a te (4l). 4l was obtained from N-(trifluoroacetyl)-
alanine and (E)-2-methyl-3-phenyl-2-butenol27 in 80% yield
(after flash chromatography, ethyl acetate/hexanes 15/85) as
a colorless oil: 1H NMR δ 7.38-7.31 (m, 2H), 7.25-7.22 (m,
1H), 7.16-7.09 (m, 2H), 7.08 (sbr, 1H), 4.88 (s, 2H), 4.68 (q, J
) 7.2 Hz, 1H), 2.03 (s, 3H), 1.61 (s, 3H); 1.54 (d, J ) 7.2 Hz,
3H); 13C NMR δ 171.6, 156.8 (q, J ) 37.6 Hz), 143.7, 137.9,
128.2, 127.8, 126.7, 125.9, 115.3 (q, J ) 287.4 Hz), 67.0, 48.8,
20.7, 18.0, 16.3. Anal. Calcd for C16H18NO3F3: C, 58.36; H,
5.51; N, 4.25. Found: C, 58.33; H, 5.39; N, 4.26.
Ger a n yl N-(ter t-Bu tyloxyca r bon yl)glycin a te (4m ). 4m
was obtained from N-(tert-butyloxycarbonyl)glycine and ge-
raniol in 88% yield (after flash chromatography, ethyl acetate/
hexanes 2/8) as a colorless oil: 1H NMR δ 5.32 (td, J ) 7.0,
1.1 Hz, 1H), 5.05 (m, 2H), 4.65 (d, J ) 7.0 Hz, 2H), 3.89 (d, J
) 5.5 Hz, 2H), 2.04 (m, 4H), 1.69 (s, 3H), 1.67 (d, J ) 1.1. Hz,
3H), 1.59 (s, 3H), 1.44 (s, 9H); 13C NMR δ 170.3, 155.7, 143.0,
131.9, 123.7, 117.8, 79.9, 62.1, 42.5, 39.5, 28.3, 26.3, 25.6, 17.6,
16.5. Anal. Calcd for C17H29NO4: C, 65.57; H, 9.39; N, 4.50.
Found: C, 65.49; H, 9.38; N, 4.51.
Ner yl N-(ter t-Bu tyloxyca r bon yl)glycin a te (4n ). 4n was
obtained from N-(tert-butyloxycarbonyl)glycine and nerol in
85% yield (after flash chromatography, ethyl acetate/hexanes
2/8) as a colorless oil: 1H NMR δ 5.32 (t, J ) 6.6 Hz, 1H), 5.05
(m, 2H), 4.61 (d, J ) 7.4 Hz, 2H), 3.87 (d, J ) 5.1 Hz, 2H),
2.06 (m, 4H), 1.74 (d, J ) 1.1 Hz, 3H), 1.66 (s, 3H), 1.57 (s,
3-Met h yl-2-b u t en yl N-(Tr iflu or oa cet yl)p h en yla la n i-
n a t e (4g). 4g was obtained from N-(trifluoroacetyl)phenyl
alanine and 3-methyl-2-butenol in 76% yield (after flash
(26) Obtained by Pd(II)-catalyzed coupling of pent-2-en-4-yn-1-ol and
iodotoluene.
(25) Neises, B.; Steglich, W. Angew. Chem. 1978, 90, 556-557.
Angew. Chem., Int. Ed. Engl. 1978, 17, 522-523
(27) Obtained by DIBAL-Reduction of the corresponding ethyl
ester: Gallagher, G., J r.; Webb, R. L. Synthesis 1974, 122.

3698 J . Org. Chem., Vol. 61, No. 11, 1996
Kazmaier
3H), 1.42 (s, 9H); 13C NMR δ 170.2, 155.6, 143.2, 132.2, 123.5,
118.6, 79.8, 61.9, 42.5, 32.1, 28.3, 26.6, 26.0, 23.4, 17.6. Anal.
Calcd for C17H29NO4: C, 65.57; H, 9.39; N, 4.50. Found: C,
65.63; H, 9.34; N, 4.55.
(s, 3H), 1.02 (s, 3H); 13C NMR δ 173.38, 155.19, 143.15, 114.68,
79.61, 63.97, 51.92, 42.35, 28.29, 23.03, 22.95, 21.82. Anal.
Calcd for C14H25NO4: C, 61.97; H, 9.25; N, 5.16. Found: C,
62.09; H, 9.24; N, 5.02.
(E)-3-Meth ylp en t-2-en -4-yn yl N-(ter t-Bu tyloxyca r bo-
n yl)glycin a te (4o). 4o was obtained from N-(tert-butyloxy-
carbonyl)glycine and (E)-3-methylpent-2-en-4-yn-1-ol in 85%
yield (after flash chromatography, ethyl acetate/hexanes 2/8)
as a pale yellow oil: 1H NMR δ 5.96 (td, J ) 7.1, 1.4 Hz, 1H),
5.05 (tbr, 1H), 4.69 (d, J ) 7.1 Hz, 2H), 3.89 (d, J ) 5.7 Hz,
2H), 2.87 (s, 1H), 1.85 (s, 3H), 1.42 (s, 9H); 13C NMR δ 170.2,
155.7, 131.1, 122.8, 85.2, 80.1, 76.4, 61.0, 42.4, 28.3, 17.5.
Anal. Calcd for C13H19NO4: C, 61.64; H, 7.56; N, 5.53.
Found: C, 61.68; H, 7.63; N, 5.65.
(Z)-3-Meth ylp en t-2-en -4-yn yl N-(ter t-Bu tyloxyca r bon -
yl)glycin a te (4p ). 4p was obtained from N-(tert-butyloxy-
carbonyl)glycine and (Z)-3-methylpent-2-en-4-yn-1-ol in 83%
yield (after flash chromatography, ethyl acetate/hexanes 2/8)
as colorless needles: mp 78°C: 1H NMR δ 5.81 (t, J ) 6.8 Hz,
1H), 5.10 (tbr, 1H), 4.80 (d, J ) 6.8 Hz, 2H), 3.87 (d, J ) 5.6
Hz, 2H), 3.19 (s, 1H), 1.87 (s, 3H), 1.40 (s, 9H); 13C NMR δ
170.2, 155.7, 131.3, 122.9, 83.2, 81.1, 79.9, 63.5, 42.3, 28.3, 22.9.
Anal. Calcd for C13H19NO4: C, 61.64; H, 7.56; N, 5.53.
Found: C, 61.36; H, 7.63; N, 5.47.
Gen er a l P r oced u r e for Ester En ola te Cla isen Rea r -
r a n gem en t. A 2.5 mmol amount of a freshly prepared LDA
solution in 5 mL of THF was added to a stirred mixture of 1
mmol of allylic ester and 1.1 mmol of the corresponding metal
salt in dry THF at -78 °C. The mixture was allowed to warm
up to room temperature overnight. The resulting clear solu-
tion was diluted with ether and hydrolyzed with 1 N hydro-
chloric acid. After separation of the aqueous layer the crude
N-protected amino acids were directly converted into the
methyl ester by addition of a solution of diazomethane in ether.
After evaporation of the solvent the crude product was purified
by flash chromatography (ethyl acetate/hexanes).
Meth yl 2-[N-(Ben zyloxyca r bon yl)a m in o]-2-ben zyl-3,3-
d im eth yl-4-p en ten oa te (5e). 5e was obtained from 4e
following the general rearrangement procedure in 69% yield
(after flash chromatography, ethyl acetate/hexanes 15/85) as
a colorless oil: 1H NMR δ 7.33 (m, 4H), 7.20-7.10 (m, 6H), 6.02
(dd, J ) 17.7, 10.5 HZ, 1H), 5.84 (sbr, 1H), 5.10 (d, J ) 12.5
Hz, 1H), 5.06 (d, J ) 17.7 Hz, 1H), 5.05 (d, J ) 10.5 Hz, 1H),
5.00 (d, J ) 12.5 Hz, 1H), 4.03 (d, J ) 14.1 Hz, 1H), 3.69 (s,
3H), 3.33 (d, J ) 14.1 Hz, 1H), 1.22 (s, 3H), 1.17 (s, 3H); 13C
NMR δ 172.4, 154.8, 144.1, 137.3, 137.1, 130.1, 130.0, 128.5,
128.1, 126.4, 113.1, 70.2, 66.2, 52.1, 46.0, 34.1, 24.2, 23.5.
Anal. Calcd for C23H27NO4: C, 72.43; H, 7.43; N, 3.67.
Found: C, 72.29; H, 7.31; N, 3.67.
Meth yl 2-[N-(ter t-Bu tyloxyca r bon yl)a m in o]-2-ben zyl-
3,3-d im eth yl-4-p en ten oa te (5f). 5f was obtained from 4f
following the general rearrangement procedure in 64% yield
(after flash chromatography, ethyl acetate/hexanes 15/85) as
a colorless oil: 1H NMR δ 7.20 (m, 5H), 6.03 (dd, J ) 16.6, 10.5
Hz, 1H), 5.68 (sbr, 1H), 5.04 (d, J ) 16.6 Hz, 1H), 5.02 (d, J )
10.6 Hz, 1H), 4.01 (d, J ) 14.0 Hz, 1H), 3.70 (s, 3H), 3.30 (d,
J ) 14.0 Hz, 1H), 1.40 (s, 9H), 1.21 (s, 3H), 1.15 (s, 3H); 13C
NMR δ 172.7, 154.4, 144.3, 137.5, 130.1, 127.9, 126.3, 112.8,
78.9, 70.0, 52.0, 46.0, 34.1, 28.4, 24.3, 23.5. Anal. Calcd for
C20H29NO4: C, 69.14; H, 8.41; N, 4.03. Found: C, 69.11; H,
8.34; N, 3.97.
Meth yl 2-[N-(Tr iflu or oa cetyl)a m in o]-2-ben zyl-3,3-d im -
eth yl-4-p en ten oa te (5g). 5g was obtained from 4g following
the general rearrangement procedure in 67% yield (after flash
chromatography, ethyl acetate/hexanes 15/85) as a colorless
1
oil: H NMR δ 7.44 (sbr, 1H), 7.20 (m, 3H), 7.09 (dd, J ) 7.0,
1.6 Hz, 2H), 6.00 (dd, J ) 17.2, 10.8 Hz, 1H), 5.12 (d, J ) 10.8
Hz, 1H), 5.10 (d, J ) 17.2 Hz, 1H), 4.08 (d, J ) 14.2 Hz, 1H),
3.80 (s, 3H), 3.40 (d, J ) 14.2 Hz, 1H), 1.26 (s, 3H), 1.22 (s,
3H); 13C NMR δ 172.0, 156.2 (q, J ) 36.2 Hz), 143.0, 135.7,
129.6, 128.3, 127.0, 115.7 (q, J ) 289.9 Hz), 114.1, 72.1, 52.7,
46.3, 33.8, 24.3, 23.6. MS (EI, 70 eV) m/ z (rel intensity) 344
(M+ + H, 1.2), 343 (M+, 0.2), 275 (12), 274 (18), 230 (31), 215
(13), 214 (55), 192 (11), 171 (13); HRMS m/ z (M+) calcd
343.1395, obsd 343.1376.
Meth yl 2-[N-(Ben zyloxyca r bon yl]a m in o]-3,3-d im eth yl-
4-p en ten oa te (5a ). 5a was obtained from 4a following the
general rearrangement procedure in 81% yield (after flash
chromatography, ethyl acetate/hexanes 15/85) as a colorless
1
oil: H NMR δ 7.34 (m, 5H), 5.81 (dd, J ) 17.3, 10.8 Hz, 1H),
5.27 (d, J ) 9.5 Hz, 1H), 5.08 (s, 2H), 5.08 (d, J ) 10.8 Hz,
1H), 5.03 (d, J ) 17.3 Hz, 1H), 4.22 (d, J ) 9.5 Hz, 1H), 3.71
(s, 3H), 1.09 (s, 6H); 13C NMR δ 171.6, 156.1, 142.8, 136.3,
128.5, 128.2, 128.1, 114.0, 67.1, 61.5, 51.8, 40.3, 24.3, 23.4.
Anal. Calcd for C16H21NO4: C, 65.96; H, 7.27; N, 4.81.
Found: C, 65.94; H, 7.31; N, 4.77.
Meth yl 2-[N-(p-Tolylsu lfon yl)a m in o]-2-ben zyl-3,3-d im -
eth yl-4-p en ten oa te (15h ) was obtained from 4h following the
general rearrangement procedure in 75% yield (after flash
chromatography, ethyl acetate/hexanes 2/8) as a colorless oil:
1H NMR δ 7.39 (d, J ) 8.4 Hz, 2H), 7.19-7.06 (m, 7H), 5.76
(dd, J ) 17.6, 10.5 Hz, 1H), 5.20 (s, 1H), 5.06 (dd, J ) 10.5,
1.1 Hz, 1H), 5.04 (dd, J ) 17.6, 1.1 Hz, 1H), 3.62 (d, J ) 15.4
Hz, 1H), 3.51 (d, J ) 15.4 Hz, 1H), 3.52 (s, 3H), 2.34 (s, 3H),
1.18 (s, 3H), 1.11 (s, 3H); 13C NMR δ 171.7, 143.3, 142.0, 140.6,
136.8, 129.6, 128.1, 126.6, 125.9, 114.8, 73.1, 51.9, 45.5, 37.3,
23.62, 23.58, 21.5. Anal. Calcd for C21H27NO4S: C, 64.76; H,
6.99; N, 3.60. Found: C, 64.72; H, 7.04; N, 3.57.
Meth yl 2-[N-(Tr iflu or oa cetyl)a m in o]-2-p h en yl-3,3-d im -
eth yl-4-p en ten oa te (5i). 5i was obtained from 4i following
the general rearrangement procedure in 78% yield (after flash
chromatography, ethyl acetate/hexanes 15/85) as a colorless
oil: 1H NMR δ 8.44 (d, J ) 7.3 Hz, 2H), 7.70 (m, 3H), 6.94 (sbr,
1H), 5.77 (dd, J ) 17.4, 10.8 Hz, 1H), 5.33 (d, J ) 10.8 Hz,
1H), 5.27 (d, J ) 17.4 Hz, 1H), 3.77 (s, 3h), 1.18 (s, 3H), 1.07
(s, 3H); 13C NMR δ 169.0, 156.3 (q, J ) 37.7 Hz), 142.7, 133.92,
127.9, 127.8, 127.7, 116.1, 115.8 (q, J ) 289.3 Hz), 68.7, 52.6,
44.5, 22.8, 22.7. Anal. Calcd for C16H18NO3F3: C, 58.38; H,
5.51; N, 4.25. Found: C, 58.33; H, 5.56; N, 4.19.
Meth yl (()-(2S,3S)-2-[N-(ter t-Bu tyloxycar bon yl)am in o]-
3-m eth yl-5-(4-m eth ylp h en yl)-3-vin yl-4-p en tyn oa te (5k ).
5k was obtained from 4k following the general rearrangement
procedure in 65% yield (after flash chromatography, ethyl
acetate/hexanes 15/85) as a colorless oil. The diastereomeric
ratio was determined by HPLC (ethyl acetate/hexanes 15/85;
tR(major): 6.12 min, tR(minor): 10.48 min): 1H NMR δ 7.34 (d, J )
8.1 Hz, 2H), 7.11 (d, J ) 8.0 Hz, 2H), 5.83 (dd, J ) 16.8, 10.0
Hz, 1H), 5.51 (d, J ) 16.8 Hz, 1H), 5.23 (dbr, 1H), 5.20 (d, J )
10.0 Hz, 1H), 4.38 (d, J ) 9.7 Hz, 1H), 3.76 (s, 3H), 2.34 (s,
Meth yl N-(ter t-Bu tyloxycar bon yl)(1′-vin ylcyclopen tyl)-
glycin a te (5b). 5b was obtained from 4b following the
general rearrangement procedure in 64% yield (after flash
chromatography, ethyl acetate/hexanes 15/85) as a colorless
1
oil: H NMR δ 5.67 (dd, J ) 17.3, 10.7 Hz, 1H), 5.15 (d, J )
10.7 Hz, 1H), 5.05 (d, J ) 17.3 Hz, 1H), 5.01 (d, J ) 9.4 Hz,
1H), 4.17 (d, J ) 9.4 Hz, 1H), 3.68 (s, 3H), 1.50-1.76 (m, 8H),
1.40 (s, 9H); 13C NMR δ 172.1, 155.5, 140.2, 115.3, 79.8, 60.2,
52.6, 51.7, 35.1, 33.3, 28.3, 23.4, 22.8. Anal. Calcd for C15H25
-
NO4: C, 63.58; H, 8.89; N, 4.94. Found: C, 63.44; H, 8.82; N,
4.87.
Meth yl N-(ter t-Bu tyloxyca r bon yl)(1′-vin ylcycloh exyl)-
glycin a te (5c). 5c was obtained from 4c following the general
rearrangement procedure in 64% yield (after flash chroma-
tography, ethyl acetate/hexanes 15/85) as a colorless oil: 1H
NMR δ 5.52 (dd, J ) 17.5, 11.0 Hz, 1H), 5.27 (dd, J ) 11.0,
1.5 Hz, 1H), 5.04 (dd, J ) 17.5, 1.5 Hz, 1H), 4.96 (dbr, J ) 9.8
Hz, 1H), 4.21 (d, J ) 9.8 Hz, 1H), 3.67 (s, 3H), 1.58-1.17 (m,
10 H), 1.38 (s, 9H); 13C NMR δ 172.0, 155.5, 140.5, 117.0, 79.7,
60.1, 51.6, 43.2, 34.0, 31.4, 28.8, 26.0, 21.9, 21.6. Anal. Calcd
for C16H27NO4: C, 64.62; H, 9.15; N, 4.71. Found: C, 64.63;
H, 8.99; N, 4.66.
Meth yl 2-[N-(ter t-Bu tyloxyca r bon yl)a m in o]-2,3,3-tr i-
m eth yl-4-p en ten oa te (5d ). 5d was obtained from 4d fol-
lowing the general rearrangement procedure in 68% yield
(after flash chromatography, ethyl acetate/hexanes 15/85) as
a colorless oil: 1H NMR δ 5.91 (dd, J ) 17.4, 10.9 Hz, 1H),
5.16 (dd, J ) 10.9, 1.0 Hz, 1H), 5.11 (dd, J ) 17.4, 1.0 Hz,
1H), 4.89 (sbr, 1H), 3.68 (s, 3H), 1.55 (s, 3H), 1.39 (s, 9H), 1.07

Quaternary Carbon-Containing Amino Acids
J . Org. Chem., Vol. 61, No. 11, 1996 3699
3H), 1.47 (s, 3H), 1.42 (s, 9H); 13C NMR δ 170.5, 155.2, 139.5,
138.3, 131.6, 129.0, 119.9, 115.8, 87.7, 86.5, 78.0, 60.4, 52.0,
43.5, 28.3, 25.4, 21.4. Anal. Calcd for C21H27NO4: C, 70.56;
H, 7.61; N 3.93. Found: C, 70.44; H, 7.56; N, 4.02.
Meth yl (()-(2S,3S)-2-[N-(Tr iflu or oacetyl)am in o]-3-ph en -
yl-2,3,4-tr im eth yl-4-p en ten oa te (5l). 5l was obtained from
4l following the general rearrangement procedure in 69% yield
(after flash chromatography, ethyl acetate/hexanes 15/85) as
a colorless oil. The diastereomeric ratio was determined by
(m, 2H), 4.22 (d, J ) 9.2 Hz, 1H), 3.80 (s, 3H), 1.91 (m, 2H),
1.65 (s, 3H), 1.56 (s, 3H), 1.41 (s, 9H), 1.38 (m, 2H), 1.04 (s,
3H); 13C NMR δ 172.0, 155.4, 141.9, 131.6, 124.2, 114.9, 79.8,
59.9, 51.7, 43.4, 37.2, 28.3, 25.6, 22.5, 19.4, 17.6. Anal. Calcd
for C18H31NO4: C, 66.43; H, 9.60; N 4.30. Found: C, 66.39;
H, 9.55; N, 4.17.
Meth yl (()-(2S,3S)-2-[N-(ter t-Bu tyloxycar bon yl)am in o]-
3-m eth yl-3-vin yl-4-p en tyn oa te (5o). 5o was obtained from
4o (and as the major product from 4p ) following the general
rearrangement procedure in 76% yield (after flash chroma-
tography, ethyl acetate/hexanes 2/8) as a pale yellow oil: 1H
NMR δ 5.74 (dd, J ) 16.8, 10.0 Hz, 1H), 5.45 (d, J ) 16.8 Hz,
1H), 5.18 (dbr, 1H), 5.17 (d, J ) 10.0 Hz, 1H), 4.28 (d, J ) 9.7
Hz, 1H), 3.75 (s, 3H), 2.41 (s, 1H), 1.40 (s, 9H), 1.39 (s, 3H);
13C NMR δ 170.4, 155.2, 139.0, 115.9, 83.1, 80.0, 74.4, 59.9,
52.0, 42.8, 28.3, 25.2. Anal. Calcd for C14H21NO4 (mixture 5o/
5p ): C, 62.90; H, 7.92; N 5.24. Found: C, 62.70; H, 7.89; N,
5.29.
Meth yl (()-(2S,3R)-2-[N-(ter t-Bu tyloxycar bon yl)am in o]-
3-m eth yl-3-vin yl-4-p en tin oa te (5p ). 5p was obtained as a
mixture with 5o from 4p (and as the minor product) following
the general rearrangement procedure in 79% yield (after flash
chromatography, ethyl acetate/hexanes 2/8) as a pale yellow
oil: 1H NMR δ 5.76 (dd, J ) 16.1, 9.8 Hz, 1H), 5.47 (d, J ) 16.1
Hz, 1H), 5.16 (m, 2H), 4.29 (d, J ) 8.8 Hz, 1H), 3.65 (s, 3H),
2.43 (s, 1H), 1.42 (s, 9H), 1.40 (s, 3H); 13C NMR δ 170.4, 155.1,
138.2, 115.7, 83.0, 80.1, 74.5, 59.9, 51.6, 43.3, 28.2, 26.1. Anal.
Calcd for C14H21NO4 (mixture 5o/5p ): C, 62.90; H, 7.92; N 5.24.
Found: C, 62.70; H, 7.89; N, 5.29.
HPLC (ethyl acetate/hexanes 7/93; tR(major): 3.07 min, tR(minor)
:
1
4.13 min): H NMR δ 7.38-7.21 (m, 5H), 7.11 (sbr, 1H), 5.35
(s, 1H), 5.31 (d, J ) 0.8 Hz, 1H), 3.31 (s, 3H), 1.95 (s, 3H),
1.71 (s, 3H), 1.59 (d, J ) 0.8 Hz, 3H); 13C NMR δ 170.8, 156.2
(q, J ) 36.7 Hz), 145.3, 141.0, 128.6, 128.5, 128.2, 127.6, 127.5,
117.6, 115.6 (q, J ) 288.8 Hz), 115.5, 66.7, 54.2, 52.3, 22.7,
21.7, 18.4. MS (EI, 70 eV) m/ z (rel intensity) 344 (M+ + H,
1.5), 343 (M+, 0.5), 275 (12), 284 (4), 171 (20), 156 (10), 146
(28), 145 (100), 133 (22), 117 (36) HRMS m/ z (M+) calcd
343.1395, obsd 343.1346.
Meth yl (()-(2S,3R)-2-[N-(ter t-Bu tyloxycar bon yl)am in o]-
3,7-d im eth yl-3-vin yl-6-octen oa te (5m ). 5m was obtained
from 4m following the general rearrangement procedure in
46% yield (after flash chromatography, ethyl acetate/hexanes
15/85) as a colorless oil: 1H NMR δ 5.73 (dd, J ) 17.3, 10.6
Hz, 1H), 5.19 (d, J ) 10.6 Hz, 1H), 5.04 (dbr, 1H), 5.03 (d, J )
17.3 Hz, 1H), 5.01 (t, J ) 10.4 Hz, 1H), 4.20 (d, J ) 9.6 Hz,
1H), 3.69 (s, 3H), 1.90 (m, 2H), 1.66, (s, 3H), 1.56 (s, 3H), 1.42
(s, 9H), 1.40 (m, 2H), 1.06 (s, 3H); 13C NMR δ 172.1, 155.4,
141.5, 131.6, 124.2, 115.4, 79.9, 60.3, 51.6, 43.4, 38.1, 28.7, 25.7,
22.6, 18.5, 17.6. Anal. Calcd for C18H31NO4: C, 66.43; H, 9.60;
N 4.30. Found: C, 66.28; H, 9.76; N, 4.22.
Meth yl (()-(2S,3S)-2-[N-(ter t-Bu tyloxycar bon yl)am in o]-
3,7-d im eth yl-3-vin yl-6-octen oa te (5n ). 5n was obtained
from 4n following the general rearrangement procedure in 43%
yield (after flash chromatography, ethyl acetate/hexanes 15/
85) as a colorless oil: 1H NMR δ 5.72 (dd, J ) 17.2, 9.9 Hz,
1H), 5.18 (t, J ) 9.5 Hz, 1H), 5.03 (d, J ) 17.3 Hz, 1H), 5.02
Ack n ow led gm en t. I thank Prof. Dr. G. Helmchen
as well as the Bayer AG for their generous support of
this work. Financial support by the Deutsche Fors-
chungsgemeinschaft as well as the Fonds der Chemis-
chen Industrie is gratefully acknowledged.
J O960014G