Straightforward stereoselective access to cyclic peptidomimetics

Article abstract of DOI:10.1021/jo900679c

(Chemical Equation Presented) The preparation of cyclic dipeptide mimetics from chiral imino lactones derived from (R)-phenylglycinol is described. Key steps of the synthetic route included the fully stereoselective construction of a quaternary center, th

Full text of DOI:10.1021/jo900679c

Straightforward Stereoselective Access to Cyclic
Peptidomimetics
Santos Fustero,*,†,‡ Natalia Mateu,†,‡ Laia Albert,†,‡ and
Jose´ Luis Acen˜a‡
Departamento de Qu´ımica Orga´nica, UniVersidad de
Valencia, E-46100 Burjassot, Spain, and Laboratorio de
Mole´culas Orga´nicas, Centro de InVestigacio´n Pr´ıncipe
Felipe, E-46012 Valencia, Spain
FIGURE 1. Structure of a ꢀ-turn.
evidence of this hydrogen bond typically serves to verify the
ꢀ-turn pattern.4 A large number of cyclic or bicyclic ꢀ-turn
mimics have been described,5 some of which exhibit biological
activities.6 Among them, Freidinger lactams are the most
emblematic example.7
santos.fustero@uV.es
ReceiVed March 31, 2009
We report herein a new synthetic route for preparing potential
ꢀ-turn mimics. The target compounds would consist of a cyclic
dipeptide framework 1 of varying ring sizes, also containing a
quaternary center that infers an additional element of constraint8
(Scheme 1). This scaffold would be constructed with the aid of
a ring-closing metathesis (RCM) reaction9 from a suitable diene
precursor 2 followed by the stereoselective introduction of a
new amino group within the ring. We used chiral imino lactones
3 as starting materials, which can be easily prepared from the
The preparation of cyclic dipeptide mimetics from chiral
imino lactones derived from (R)-phenylglycinol is described.
Key steps of the synthetic route included the fully stereo-
selective construction of a quaternary center, the formation
of six-, seven-, or eight-membered lactams by means of an
RCM cyclization, and the introduction of a new amino group
within the lactam ring. The synthesis of a tripeptide mimetic
is also reported.
(4) (a) Belvisi, L.; Gennari, C.; Mielgo, A.; Potenza, D.; Scolastico, C. Eur.
J. Org. Chem. 1999, 389–400. (b) Vass, E.; Hollo´si, M.; Besson, F.; Buchet, R.
Chem. ReV. 2003, 103, 1917–1954.
(5) For recent examples, see: (a) San˜udo, M.; Garc´ıa-Valverde, M.; Mar-
caccini, S.; Delgado, J. J.; Rojo, J.; Torroba, T. J. Org. Chem. 2009, 74, 2189–
2192. (b) Li, Y.; Yu, Y.; Giulianotti, M.; Houghten, R. A. J. Org. Chem. 2009,
74, 2183–2185. (c) Scheffelaar, R.; Nijenhuis, R. A. K.; Paravidino, M.; Lutz,
M.; Spek, A. L.; Ehlers, A. W.; de Kanter, F. J. J.; Groen, M. B.; Orru, R. V. A.;
Ruijter, E. J. Org. Chem. 2009, 74, 660–668. (d) Deaudelin, P.; Lubell, W. D.
Org. Lett. 2008, 10, 2841–2844. (e) Angell, Y.; Chen, D.; Saragovi, H. U.;
Burgess, K. J. Am. Chem. Soc. 2008, 130, 556–565. (f) Lomlin, L.; Einsiedel,
J.; Heinemann, F. W.; Meyer, K.; Gmeiner, P. J. Org. Chem. 2008, 73, 3608–
3611. (g) Verdie´, P.; Subra, G.; Averland-Petit, M.-C.; Amblard, M.; Martinez,
J. J. Comb. Chem. 2008, 10, 869–874. (h) Lesma, G.; Colombo, A.; Sacchetti,
A.; Silvani, A. Tetrahedron Lett. 2008, 49, 7423–7425. (i) Palomo, C.; Aizpurua,
J. M.; Balentova´, E.; Jime´nez, A.; Oyarbide, J.; Fratila, R. M.; Miranda, J. I.
Org. Lett. 2007, 9, 101–104. For reviews, see: (j) Souers, A. J.; Ellman, J. A.
Tetrahedron 2001, 57, 7431–7448. (k) MacDonald, M.; Aube´, J. Curr. Org.
Chem. 2001, 5, 417–438. (l) Burgess, K. Acc. Chem. Res. 2001, 34, 826–835.
(m) Pe´rez de Vega, M. J.; Mart´ın-Mart´ınez, M.; Gonza´lez-Mun˜iz, R. Curr. Top.
Med. Chem. 2007, 7, 33–62.
The search for new peptidomimetic structures is a common
approach to obtain drug-like compounds derived from biologi-
cally active peptides.1 One of the most pursued strategies
consists of the preparation of cyclic analogues in order to reduce
the conformational freedom of the parent peptides.2 In this
context, many conformationally constrained mimics of reverse
turns have been designed and synthesized, considering that turns
are ubiquitous structural motifs in peptides and proteins and
are also essential for folding and molecular recognition events.3
Among all types of reverse turns, ꢀ-turns are the most
frequent and extensively studied. They involve four amino acid
residues and are usually stabilized by an intramolecular hydro-
gen bond that forms a 10-membered ring (Figure 1). In fact,
(6) (a) To¨mbo¨ly, C.; Ballet, S.; Feytens, D.; Ko¨ve´r, K. E.; Borics, A.; Lovas,
S.; Al-Khrasani, M.; Fu¨rst, Z.; To´th, G.; Benhye, S.; Tourwe´, D. J. Med. Chem.
2008, 51, 173–177. (b) Vartak, A. P.; Skoblenick, K.; Thomas, N.; Mishra, R. K.;
Johnson, R. L. J. Med. Chem. 2007, 50, 6725–6729. (c) Cai, M.; Cai, C.;
Mayorov, A. V.; Xiong, C.; Cabello, C. M.; Soloshonok, V. A.; Swift, J. R.;
Trivedi, D.; Hruby, V. J. J. Peptide Res. 2004, 63, 116–131. (d) Qiu, W.; Gu,
X.; Soloshonok, V. A.; Carducci, M. D.; Hruby, V. J. Tetrahedron Lett. 2001,
42, 145–148.
(7) (a) Freidinger, R. M.; Veber, D. F.; Perlow, D. S.; Brooks, J. R.;
Saperstein, R. Science 1980, 210, 656–658. (b) Freidinger, R. M. J. Med. Chem.
2003, 46, 5553–5566.
(8) For previous synthetic approaches to molecules related to 1, see:(a)
Westermann, B.; Diedrichs, N.; Krelaus, R.; Walter, A.; Gedrath, I. Tetrahedron
Lett. 2004, 45, 5983–5986. (b) Cordero, F. M.; Pisaneschi, F.; Meschini Batista,
K.; Valenza, S.; Machetti, F.; Brandi, A. J. Org. Chem. 2005, 70, 856–867. (c)
Verbist, B. M. P.; De Borggraeve, W. M.; Toppet, S.; Compernolle, F.; Hoornaert,
G. J. Eur. J. Org. Chem. 2005, 2941–2950.
(9) The use of metathesis reactions in peptidomimetic synthesis has been
recently reviewed; see: (a) Brik, A. AdV. Synth. Catal. 2008, 350, 1661–1675.
For selected examples, see: (b) Fink, B. E.; Kym, P. R.; Katzenellenbogen, J. A.
J. Am. Chem. Soc. 1998, 120, 4334–4344. (c) Hoffmann, T.; Lanig, H.; Waibel,
R.; Gmeiner, P. Angew. Chem., Int. Ed. 2001, 40, 3361–3364. (d) Creighton,
C. J.; Leo, G. C.; Du, Y.; Reitz, A. B. Bioorg. Med. Chem. 2004, 12, 4375–
4385.
† Universidad de Valencia.
‡ Centro de Investigacio´n Pr´ıncipe Felipe.
(1) (a) Adessi, C.; Soto, C. Curr. Med. Chem. 2002, 9, 963–978. (b) Hummel,
G.; Reineke, U.; Reimer, U. Mol. BioSyst. 2006, 2, 499–508. (c) Che, Y.; Brooks,
B. R.; Marshall, G. R. J. Comput. Aided Mol. Des. 2006, 20, 109–130. (d) Vagner,
J.; Qu, H.; Hruby, V. J. Curr. Opin. Chem. Biol. 2008, 12, 292–296.
(2) For reviews, see: (a) Hanessian, S.; McNaughton-Smith, G.; Lombart,
H.-G.; Lubell, W. D. Tetrahedron 1997, 53, 12789–12854. (b) Soloshonok, V. A.
Curr. Org. Chem. 2002, 6, 341–364. (c) Belvisi, L.; Colombo, L.; Manzoni, L.;
Potenza, D.; Scolastico, C. Synlett 2004, 1449–1471. (d) Cluzeau, J.; Lubell,
W. D. Biopolymers 2005, 80, 98–150. (e) Maison, W.; Prenzel, A. H. G. P.
Synthesis 2005, 1031–1048. (f) Hanessian, S.; Auzzas, L. Acc. Chem. Res. 2008,
41, 1241–1251.
(3) Rotondi, K. S.; Gierasch, L. M. Biopolymers 2006, 84, 13–22.
10.1021/jo900679c CCC: $40.75
Published on Web 05/13/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 4429–4432 4429

SCHEME 1. Synthetic Plan
SCHEME 3. Synthesis of Bicyclic Lactams 5c-e
SCHEME 2. Synthesis of Bicyclic Lactam 5a
SCHEME 4. Synthesis of Eight-Membered Lactam 9
condensation of the corresponding R-keto esters with (R)-phenyl-
glycinol.10-12 These dipeptide mimetics 1 are suitable for further
elongations at both C- and N-termini in order to complete the
ꢀ-turn arrangement.
To test the feasibility of our strategy, we first employed
unsaturated imine 3a, available from ethyl 2-oxohex-5-enoate13
and (R)-phenylglycinol (Scheme 2). Thus, chemo- and stereo-
selective addition10 of MeMgBr mediated by BF3 ·OEt2 afforded
morpholinone 4a as a single isomer, having the phenyl and
methyl groups in trans relationship.14,15 Next, reaction of 4a
with acryloyl chloride led to diene 2a, which in turn easily
cyclized in the presence of second generation Grubbs catalyst
to produce the corresponding RCM compound 5a.
We next explored the possibility of accessing other ring sizes
and stereochemical arrangements. Since imino lactones related
to 3a containing allyl or vinyl groups are difficult to obtain, we
decided to develop a common synthetic route starting from the
previously reported methyl imine 3b10 (Scheme 3). Thus,
addition of vinyl-, allyl-, but-3-enyl-, and pent-4-enylmagnesium
bromides afforded compounds 4b-e,16 which were then con-
verted into acrylamides 2b-e. However, the subsequent RCM
reaction (second generation Grubbs catalyst, refluxing CH2Cl2)
only proceeded satisfactorily in the case of six- and seven-
membered rings to give compounds 5c and 5d, respectively.
The corresponding five-membered compound 5b was not
detected,17 most probably due to the highly congested structure
of the diene precursor18 and the presence of the quaternary
center, whereas eight-membered product 5e was obtained in low
yield using refluxing toluene.
An alternative approach to the five- and eight-membered rings
would be the prior opening of the lactone before the RCM
process in order to eliminate any element of constraint that might
preclude the cyclization step. Thus, reduction of lactone 4e with
LiBH4 followed by TBS protection of the resulting diol 6
afforded bis-silyl ether 7 (Scheme 4). In this case, the derived
acrylamide 8 smoothly cyclized to produce eight-membered
lactam 9. In contrast, the preparation of the corresponding five-
membered compound using a similar sequence was yet again
ineffective.
(10) Harwood, L. M.; Vines, K. J.; Drew, M. G. B. Synlett 1996, 1051–
1053.
(11) We have recently used imines 3 in the preparation of optically pure
ꢀ-amino-R-trifluoromethyl alcohols by means of the addition of TMSCF3 to the
lactone moiety. See: Fustero, S.; Albert, L.; Acen˜a, J. L.; Sanz-Cervera, J. F.;
Asensio, A. Org. Lett. 2008, 10, 605–608.
(12) Related chiral templates such as Williams’ diphenyloxazinones have
also been used in the synthesis of quaternary amino acids; see: Williams, R. M.;
Zhai, W. Tetrahedron 1988, 44, 5425–5430.
(13) Macritchie, J. A.; Silcock, A.; Willis, C. L. Tetrahedron: Asymmetry
1997, 8, 3895–3902.
(14) The configuration of the new stereogenic center was assumed as depicted
according to previous results (see ref 10) and confirmed in subsequent
transformations carried out. Moreover, the stereochemical integrity was preserved
in the Grignard addition step as determined by chiral HPLC analysis of
compounds 4.
(15) A diastereoselective radical addition of alkyl groups to iminolactones 3
was also reported; see: Miyabe, H.; Yamaoka, Y.; Takemoto, Y. J. Org. Chem.
2005, 70, 3324–3327.
(17) Other conditions tested included the use of Grubbs second generation
catalyst in the presence of Ti(O-i-Pr)4, Grubbs-Hoveyda catalyst, or heating
under microwave irradiation. In all cases the starting material was recovered
unchanged.
(18) Preparation of five-membered lactams fused with other rings by means
of RCM are very scarce in the literature; see: (a) Lim, S. H.; Ma, S.; Beak, P.
J. Org. Chem. 2001, 66, 9056–9062. (b) Muroni, D.; Mucedda, M.; Saba, A.
Tetrahedron Lett. 2008, 49, 2373–2376.
(16) For the synthesis of a trifluoromethyl analogue of 4c, see: Chaume, G.;
Van Severen, M.-C.; Marinkovic, S.; Brigaud, T. Org. Lett. 2006, 8, 6123–
6126.
4430 J. Org. Chem. Vol. 74, No. 11, 2009

SCHEME 5. Functionalizations of Lactams 5a and 5c
SCHEME 6. Synthesis of Tripeptide 20
out in both 12 and 13 (see Supporting Information). A similar
sequence or reactions from six-membered lactam 5c led to
N-Boc-protected amines 15 and 16, also with good selectivity.
In this case, the configuration of the amino group was deduced
by coupling constant measurements.
The observed selectivity in the hydrogenation of lactams 11 and
14 may be rationalized by the blocking effect of the methyl group,
which hinders one of the faces of the double bond. Thus, the methyl
and BocNH groups are displayed in cis relationship in the resulting
major diastereoisomers 12 and 15, respectively. Conversely, the
different behavior toward hydrogenation of vinyl azide 10 and
N-Boc amine 11 could possibly originate from the much larger
steric size of the BocNH group in the latter compound.
Finally, we carried out the removal of the chiral auxiliary by
reduction of bicyclic lactam 12 to diol 17,20 followed by
hydrogenation to monocyclic lactam 18 and reoxidation to obtain
carboxylic acid 19 (Scheme 6). This compound constitutes a
cyclic analogue of dipeptide Boc-Gly-Ala-OH, and the Boc
protecting group may act as a surrogate of the amino acid i of
a ꢀ-turn structure. To complete the ꢀ-turn pattern, the introduc-
tion of a new amino acid residue (i + 3) took place through the
condensation of 19 with glycine methyl ester to finally obtain
tripeptide mimetic 20.21
The following step was to locate an amino group next to the
lactam carbonyl in compounds 5 or 9.19 After much experi-
mentation, functionalization of the double bond in compound
5a was most efficiently carried out by reaction with Br2, thus
producing a mixture of diastereoisomeric dibromides that were
then converted into vinyl azide 10 (Scheme 5). At this point,
hydrogenation of the double bond and the azide functionality
in the presence of Boc2O furnished an equimolecular mixture
of epimers 12 and 13, regardless of the different reaction
conditions examined (catalyst, solvent, and hydrogen pressure).
However, a much more selective result was achieved in a two-
step process through the partial reduction of the azide to the
corresponding N-Boc-amine 11 (5 mol % Pd(OH)2, 5 min)
followed by the further hydrogenation of the double bond at
high pressure to give 12 as the major product with 90:10
selectivity. Both epimers were easily separated by column
chromatography, and the configuration of the newly created
stereogenic center was deduced by NOE correlations carried
In summary, an efficient access to cyclic dipeptide structures
from simple, chiral templates derived from (R)-phenylglycinol
has been developed. These compounds could represent the
central segment of prospective cyclic ꢀ-turn scaffolds. Further
synthetic work and conformational analysis of the target
peptidomimetics are in progress.
Experimental Section
(4R,10aS)-10a-Methyl-4-phenyl-3,4,10,10a-tetrahydro-1H-[1,4]ox-
azino[4,3-a]azepine-1,6(9H)-dione (5a). Grubbs second generation
(19) Direct coupling of amine 4a with a N-Boc-protected dehydroalanine
failed to provide a RCM precursor of compound 11.
(20) Base-mediated transesterification or hydrogenolysis at high pressure of
the lactone ring in 12 failed to give the corresponding hydroxy ester or hydroxy
acid.
(21) Related seven-membered lactams were prepared by Holmes and co-
workers, although lacking the quaternary center. In their work, the cis
diastereoisomer had an extended conformation, whereas the trans isomer formed
a ꢀ-turn structure. See: Nadin, A.; Derrer, S.; McGeary, R. P.; Goodman, J. M.;
Raithby, P. R.; Holmes, A. B.; O’Hanlon, P. J.; Pearson, N. D. J. Am. Chem.
Soc. 1995, 117, 9768–9769.
J. Org. Chem. Vol. 74, No. 11, 2009 4431

catalyst (107 mg, 0.13 mmol) was added to a solution of 2a (754
mg, 2.52 mmol) in CH2Cl2 (60 mL). The mixture was heated at
reflux for 2 h, allowed to cool to room temperature, and concen-
trated at reduced pressure. The product was purified by column
chromatography on silica to afford 648 mg of 5a as a white solid
63.5, 68.2, 79.6, 127.2, 128.2, 129.0, 135.9, 155.2, 171.4, 172.7.
HRMS (EI) calcd for C21H28N2O5 [M]+ 388.1998; found 388.2003.
Methyl 2-((2S,6R)-6-(tert-Butoxycarbonylamino)-2-methyl-7-
oxoazepane-2-carboxamido)acetate (20). NaIO4 (706 mg, 3.30
mmol) and RuCl3 ·2H2O (2 mg, 0.01 mmol) were added to a
solution of 18 (90 mg, 0.33 mmol) in 2:1:1.5 MeCN/CH2Cl2/H2O
(3.3 mL) at 0 °C. The mixture was stirred at 0 °C for 3 h, and then
H2O was added. The aqueous layer was extracted with CH2Cl2,
and the combined organic layers were dried over Na2SO4, filtered,
and concentrated at reduced pressure. The crude acid 19 was
dissolved in DMF (2.4 mL) and DIC (0.07 mL, 0.48 mmol), HOBt
(65 mg, 0.48 mmol), H-Gly-OMe ·HCl (60 mg, 0.48 mmol), and
DMAP (15 mg, 0.12 mmol) were added. The mixture was stirred
at room temperature for 12 h and then H2O was added. The aqueous
layer was extracted with EtOAc, and the combined organic layers
were dried over Na2SO4, filtered, and concentrated at reduced
pressure. The product was purified by column chromatography on
silica to afford 54 mg of 20 as a white solid (45% yield). Rf 0.23
(95% yield). Rf 0.16 (hexane/EtOAc, 2:1). Mp: 208-209 °C. [R]25
D
-30.7 (c 0.9, CHCl3). 1H NMR (300 MHz, CDCl3) δ 1.70 (s, 3H),
2.07 (ddd, J ) 15.5, 11.3, 5.9 Hz, 1H), 2.44-2.69 (m, 2H), 3.11
(dddd, J ) 14.9, 6.0, 3.2, 1.2 Hz, 1H), 4.84 (dd, J ) 12.0, 2.6 Hz,
1H),4.89 (dd, J ) 12.0, 2.6 Hz, 1H), 5.93 (br, 1H), 6.13 (dq, J )
12.5, 1.3 Hz, 1H), 6.34 (dtd, J ) 12.5, 3.9, 0.9 Hz,1H), 7.24-7.37
(m, 5H). 13C NMR (75 MHz, CDCl3) δ 22.5, 27.2, 34.7, 53.7, 61.5,
69.3, 126.7, 126.7, 128.0, 128.9, 136.9, 140.9, 165.9, 171.5. HRMS
(FAB) calcd for C16H18NO3 [M + 1]+ 272.1287; found 272.1292.
(4R,7R,10aS)-7-(tert-Butoxycarbonylamino)-10a-methyl-4-phe-
nylhexahydro-1H-[1,4]oxazino[4,3-a]azepine-1,6(7H)-dione (12) and
(4R,7S,10aS)-7-(tert-Butoxycarbonylamino)-10a-methyl-4-phenyl-
hexahydro-1H-[1,4]oxazino[4,3-a]azepine-1,6(7H)-dione (13). Pd-C
(10 wt %, 68 mg, 0.64 mmol) was added to a solution of 11 (200
mg, 0.64 mmol) in MeOH (12.8 mL). The mixture was stirred under
H2 atmosphere (40 atm) for 18 h, filtered, and concentrated at
reduced pressure. The product was purified by column chromatog-
raphy on silica to afford 157 mg of 12 (63% yield) and 17 mg of
(hexane/EtOAc, 1:10). Mp: 151-152 °C. [R]25 -13.7 (c 1.0,
D
1
CHCl3). H NMR (300 MHz, CDCl3) δ 1.39 (s, 9H), 1.33-1.46
(m, 2H), 1.50 (s, 3H), 1.72-2.09 (m, 3H), 2.46 (dt, J ) 14.3, 3.3
Hz, 1H), 3.69 (s, 3H), 3.92-4.19 (m, 3H), 5.62 (d, J ) 5.8 Hz,
1H), 6.75 (s, 1H), 7.23 (t, J ) 5.5 Hz, 1H). 13C NMR (75 MHz,
CDCl3) δ 23.7, 28.3, 30.3, 30.5, 37.9, 41.4, 52.2, 54.5, 60.2, 79.4,
154.8, 170.2, 173.1, 175.8. HRMS (FAB) calcd for C16H28N3O6
[M + 1]+ 358.1978; found 358.1961.
13 (7% yield), both as white solids. Data for 12: Rf 0.22 (hexane/
1
EtOAc, 2:1). Mp: 106-107 °C. [R]25 -77.2 (c 1.2, CHCl3). H
D
NMR (300 MHz, CDCl3) δ 1.41 (s, 9H), 1.82 (s, 3H), 1.87-2.04
(m, 2H), 2.05-2.22 (m, 1H), 2.22-2.46 (m, 2H), 3.07 (dd, J )
16.3, 5.2 Hz, 1H), 4.19 (d, J ) 9.0 Hz, 1H), 4.49 (dd, J ) 12.0,
1.3 Hz, 1H), 5.08 (dd, J ) 12.4, 3.4 Hz, 1H), 5.54 (d, J ) 2.0 Hz,
1H), 5.83 (br, 1H), 7.08 (d, J ) 6.9 Hz, 2H), 7.26-7.42 (m, 3H).
13C NMR (75 MHz, CDCl3) δ 18.6, 25.1, 28.0, 28.3, 32.2, 54.1,
57.2, 63.4, 68.9, 79.6, 125.2, 127.8, 129.0, 139.8, 155.4, 170.7,
172.0. HRMS (EI) calcd for C21H28N2O5 [M]+ 388.1998; found
Acknowledgment. We thank the Ministerio de Educacio´n y
Ciencia (CTQ2007-61462) and Generalitat Valenciana (GVPRE/
2008/013) for their financial support. N.M. and L.A. thank the
Universidad de Valencia for predoctoral fellowships, and J.L.A.
thanks the MEC for a Ramo´n y Cajal research contract.
388.1990. Data for 13: Rf 0.34 (hexane/EtOAc, 2:1). Mp: 123-124
1
°C. [R]25 -86.5 (c 1.1, CHCl3). H NMR (300 MHz, CDCl3) δ
Supporting Information Available: Experimental proce-
dures and characterization data and NMR spectra for all new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
D
1.34-1.60 (m, 1H), 1.44 (s, 9H), 1.64-2.19 (m, 4H), 1.86 (s, 3H),
2.55 (d, J ) 13.9 Hz, 1H), 4.60 (ddd, J ) 12.1, 6.8, 2.6 Hz, 1H),
4.80 (dd, J ) 12.1, 2.7 Hz, 1H), 4.89 (dd, J ) 12.1, 1.8 Hz, 1H),
5.88 (d, J ) 6.8 Hz, 1H), 6.02 (br, 1H), 7.22-7.40 (m, 5H). 13C
NMR (75 MHz, CDCl3) δ 21.5, 24.8, 28.3, 31.9, 36.0, 53.0, 54.6,
JO900679C
4432 J. Org. Chem. Vol. 74, No. 11, 2009