Total Syntheses of (+)- and (-)-Tetrapetalones A and C

Article abstract of DOI:10.1021/jacs.7b09358

Described herein are syntheses of the naturally occurring polyketides (-)-tetrapetalones A and C and their respective enantiomers. The employed strategy involves initial assembly of a masked N-aryl tetramic acid which is advanced via a highly selective conjugate addition/intramolecular Friedel-Crafts acylation sequence to deliver a key azepine intermediate. Application of recently developed C-H activation chemistry and subsequent Heck cyclization delivers the aglycone framework in an overall 12 steps. Resolution of the aglycone via stereospecific glycosylation with an enantiopure glycosyl donor followed by separation of the derived diastereomers enables further advancement to either (+)- or (-)-tetrapetalones A and C.

Full text of DOI:10.1021/jacs.7b09358

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Communication
Total Syntheses of (+)-and (-)-Tetrapetalones A and C
Heemal H. Dhanjee, Yutaka Kobayashi, Jonas F. Buergler, Travis C. McMahon,
Matthew W. Haley, Jennifer M. Howell, Koichi Fujiwara, and John L. Wood
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b09358 • Publication Date (Web): 09 Oct 2017
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Total Syntheses of (+)-and (-)-Tetrapetalones A and C
Heemal H. Dhanjee, Yutaka Kobayashi, Jonas F. Buergler, Travis C. McMahon, Matthew W. Haley,
Jennifer M. Howell, Koichi Fujiwara, and John L. Wood*
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Department of Chemistry and Biochemistry, Baylor University, One Bear Place 97348, Waco, Texas 76798, USA
Supporting Information Placeholder
the tetrapetalones. Despite elegant work from the
ABSTRACT: Described herein are syntheses of the natu-
groups of Sarpong (Figure 1c),4 Porco,5 Pettus,6 Hong,7
rally occurring polyketides (-)-tetrapetalones A and C
and most recently Frontier,8 a completed total synthesis
and their respective enantiomers. The employed strategy
has yet to be realized. Perhaps most significant among
these are the efforts of Frontier who prepared an O-
methyl derivative of racemic tetrapetalone A aglycone in
a 27-step sequence (Figure 1d).8 However, neither de-
methylation of this intermediate nor further advance-
ment toward the natural product were reported. Herein
we detail our efforts which culminate in complete syn-
theses of (+)- and (-)-tetrapetalones A and C in 18- and
19-steps, respectively.
involves initial assembly of a masked N-aryl tetramic
acid which is advanced via a highly selective conjugate
addition/intramolecular Friedel-Crafts acylation se-
quence to deliver a key azepine intermediate. Applica-
tion of recently developed C-H activation chemistry and
subsequent Heck cyclization delivers the aglycone
framework in an overall 12 steps. Resolution of the
aglycone via stereospecific glycosylation with an enan-
tiopure glycosyl donor followed by separation of the
derived diastereomers enables further advancement to
either (+)- or (-)-tetrapetalones A and C.
From the outset, our primary motivation for pursuing
a synthesis of the tetrapetalones was the synthetic chal-
lenge posed by the array of functional groups embedded
within the compact structure of 1. Of particular note are
the stereogenic p-quinol, four contiguous stereocenters,
and trisubstituted olefin found in the fused azepine, a
seemingly simple structural element that proved quite
challenging in the Sarpong and Frontier efforts. The
lack of C2’ functionality on the β-linked rhodinose moi-
ety presented an additional challenge as this severely
limits the number of methods one could hope to effec-
tively employ for stereoselective glycosylation.
In their pursuit of novel lipoxygenase inhibitors, Hiro-
ta and co-workers isolated tetrapetalone A (1, Figure 1a)
from Streptomyces sp. USF-4727 in 2003.1 Subsequent
studies led to the discovery of a small family of conge-
ners, tetrapetalones B-D (2-4), which differ in their oxi-
dation states at the pendant ethyl sidechain, the tetramic
acid moiety, or both, respectively.2 More recently, Hiro-
ta reported the isolation of ansaetherone (5), a presumed
biosynthetic precursor to the tetrapetalones.3
Scheme 1. Retrosynthetic analysis of tetrapetalone A
Crotylation
Glycosylation
H
H
Et
O
Et
O
O
OH
OH
HO
O
N
N
O
CO2Et
HO
OTIPS
O
Phenolic Oxidation
CꢀH Activation/Heck
tetrapetalone A (1)
6
Dieckmann Cyclization
O
FriedelꢀCrafts
Acylation
Et
O
Et
O
O
N
N
CO2Et
O
H
+
CO2Et
O
OTIPS
OTIPS
9
7
8
Taking into account the numerous synthetic challeng-
es, a strategy evolved wherein a late-stage glycosylation,
aryl-oxidation, and decarboethoxylation sequence ap-
plied to aglycone 6 would deliver the natural product
Figure 1. The tetrapetalones
In the roughly 15 years since their isolation, consider-
able effort has been focused on developing syntheses of
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Page 2 of 6
(Scheme 1). Based on recent advances in C-H function-
by Yamamoto and pre-complexed 8 with the sterically
encumbered Lewis acid aluminum tris(2,5-
1
2
3
4
5
6
7
8
alization, aglycone 6 was envisioned as arising from
enone 7, which proved to be readily accessible from
masked tetramic acid 9 via conjugate addition with
methacrolein (8) and subsequent Friedel-Crafts acyla-
tion. As was determined empirically, the ultimate suc-
cess of this sequence hinged critically on the strategy
employed for masking inherent acidity in the N-aryl
tetramic acid. To this end, methyl enolether variants
akin to those prepared by Frontier (See Figure 1d) were
initially explored, however, difficulties associated with
unmasking led to our quaternizing the central carbon
with an ethoxycarbonyl moiety (see compound 9).9
diphenylphenoxide) (ATPH).12 The resultant complex
14 was found to undergo selective 1,4-addition to give
an intermediate enolate (15) that, upon oxidation with
molecular bromine, furnishes a product (16) which is
poised for conversion to the requisite azepine via cy-
clization and base promoted elimination. 13
To set the stage for ring closure, aldehyde 16 was
converted to the corresponding carboxylic acid under
Pinnick oxidation conditions. Although a number of
strategies were found to be effective for advancing the
aforementioned acid, the Friedel-Crafts conditions of
Aubé (simple heating of the appropriate acid chloride in
HFIP, Scheme 2) were found to be most effective.14
This method allowed for simple solvent exchange prior
to the DBU promoted elimination that transforms the
intermediate α-bromoketone to key intermediate 7 (73%
yield, one-pot).15
9
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12
13
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17
18
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In implementing the synthetic strategy we began by
exploring numerous approaches to the masked tetramic
acid (9).10 The most efficient result of our efforts is il-
lustrated in Scheme 2 and begins by alkylating 3-
aminophenol (10) with butanoate 11. Protection of the
derived phenol as the TIPS-ether followed by exposure
to acid chloride 12 delivers Dieckmann cyclization pre-
cursor 13. After some experimentation it was found that
treating 13 with DBU in the presence of 4Å molecular
sieves efficiently delivers the desired lactam 9 in 83-
95% yield (65-74% over three steps from readily availa-
ble commercial materials).11
Having developed an approach capable of efficiently
delivering multigram quantities of 7 we next focused on
further aryl functionalization. To this end, we became
intrigued by reports from Rao and Dong describing ke-
tone directed C-H hydroxylation reactions.16 Prelimi-
nary studies of conditions reported by both laboratories
revealed that using 5 mol% Pd(TFA)2 and phenyl iodine
bis(trifluoroacetate) (PIFA) as reported by Dong was
very effective in converting 7 to the desired phenol 17
(88% yield). Importantly, these conditions proved ame-
nable to multigram-scale reactions and delivered materi-
al that could be advanced without purification through a
three-step sequence leading to Heck cyclization precur-
Turning toward introduction of the azepine ring we
sought to employ a 1,4-addition/intramolecular Friedel-
Crafts acylation sequence. Initial investigations into the
reaction of 9 with methacrolein (8) under standard con-
ditions resulted in predominantly 1,2-addition and only
low yields of the desired 1,4-adduct. To suppress the
1,2-addition pathway we turned to chemistry developed
Scheme 1. Preparation of the tetrapetalone A-aglycone carbocyclic framework
Ph
O
Al
O
3
(OAr)3
Et
O
O
Ph
14
1. Et
O
O
O
H
Et
H
Br
Et
11
NH2
DBU
4Å M.S.
O
60 o
C
O
then Br2
DMF,
NaHMDS
THF
N
N
CO2Et
CO2Et
2. i. TIPSCl, imid., CH2Cl2
THF, reflux
N
O
O
O
OH
CO2Et
ii. Cl
CO2Et
OTIPS
OTIPS
O
12
OTIPS
10
13
(83ꢀ95% yield)
9
15
(95% yield)
DMAP (cat.)
(79% yield, two steps)
O
Br
1. NaClO2, H2O2
NaH2PO4•H2O
CH3CN, H2O
[Pd(TFA)2], PIFA
DCE, 80 °C
then SiO2
H
1. CeCl3•7H2O, NaBH4
2. BF3•OEt2
Et
Et
O
O
O
Et
O
O
O
O
Et
TMS
O
O
HO
N
N
N
2. (COCl)2, DMF (cat.)
then HFIP, ꢁW
then DBU, TIPSCl
N
CO2Et
CO2Et
CO2Et
CO2Et
O
O
(73% yield,
two steps)
OTIPS
7 (dr = 2.8:1)
OTIPS
17
OTIPS
18
(69% yield, two steps)
OTIPS
16
(88% yield)
H
8
H
8
H
8
H
Et
O
Et
Et
O
O
O
i.
Pd(PPh3)4 (10 mol%)
Et3N (250 mol%)
Et
O
O
8
Tf2O, pyr.
ii
iii
.
.
then DMDO
then NaIO4
HO
HO
TfO
N
N
N
N
CH3CN
ꢁW, 100 °C
8 h
CO2Et
CO2Et
CO2Et
CO2Et
CH3CN:H2O, 50 °C
O
O
(93% yield)
(68% yield)
OTIPS
19a
OTIPS
C8: dr = 1:8 (19a:19b) 19b
OTIPS
OTIPS
22a/b
(C8 dr = 1:8, respectively)
[gramꢀscale]
H
21a/b
(C8 dr = 1:8, respectively)
H
H
Et
O
O
Et
O
Et
O
O
NaBH4
CeCl3•7H2O
TBAF
HO
O
HO
N
N
N
CO2Et
CO2Et
CO2Et
O
OH
20
OTIPS
(±)ꢀ6
OTIPS
23
(only observed product)
(quant. yield)
(92% yield)
entꢀ20
(12% overall yield, 12 steps
based on 2.8:1 dr in preparation of 7)
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sors 19a,b (73% yield). In the latter sequence, Luche
Scheme 2. Stereospecific glycosylation and comple-
1
2
3
4
5
6
7
8
reduction of 17 was found to selectively provide an un-
stable benzylic alcohol which, upon exposure to
BF3•OEt2 in the presence of trans-crotyl silane furnishes
a 1:8 mixture of adducts 19a:19b, respectively, presum-
ably via o-quinone methide intermediate (18). As has
proven typical, this azepine system reacts selectively on
the beta-face and thus the mixture results from differ-
ences at the homobenzylic stereocenter.17 Crystalline
derivative 20 was prepared to confirm the illustrated
relative stereochemistries. Subsequent triflation of
19a/b furnished 21 as the major component in an 8:1
mixture of diastereomers. Exposure of this mixture to
Heck conditions under standard (24 h) or microwave (8
h) heating furnished 22 which, after solvent exchange,
was then sequentially treated with DMDO and aqueous
sodium periodate to provide tetracyclic ketone 23 as the
only isolable diastereomer (65% yield from 21, >20:1
tion of (-)-tetrapetalone A
9
10
11
12
13
14
15
16
17
18
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1
To our dismay, initial H and 13C NMR data obtained
,
dr).18 19 Diastereoselective reduction, again utilizing Lu-
che conditions,20 gave the desired glycosylation sub-
for (-)-1 failed to compare satisfactorily to data in the
literature; major differences were observed in the spec-
tral regions associated with the tetramic acid moiety.
Suspicious that keto-enol tautomerism was the culprit,
subsequent spectra were collected following treatment
of the samples with dilute formic acid which, to our de-
light, resulted in data that was in complete accord with
that reported for (-)-tetrapetalone A.29
strate (±)-6 in 92% yield.
With a suitable aglycone precursor in hand (i.e. (±)-6),
attention was turned to stereoselectively installing the β-
rhodinose moiety (Scheme 3). Inspired by an Organic
Syntheses procedure from O’Doherty that had been
checked in our laboratory, we chose to attempt glycosyl-
ation with anomeric allylic carbonate 24 under condi-
tions that would proceed stereospecifically via a double
Scheme 3. Preparation of ent-tetrapetalone A
,
invertive mechanism.21 22 In practice this glycosylation
protocol proved highly effective in coupling (±)-6 with
(+)-β-D-Boc-pyranone 24 (98% ee)23 and delivered only
the β−anomers of the diastereomeric enone products (+)-
25a and (-)-25b (84% yield). Fortunately this 1:1 mix-
ture of diastereomers proved readily separable thus ena-
bling resolution of the aglycone and eventual completion
of both natural and enantiomeric tetrapetalone A, (-)-
and (+)-1, respectively. 24
To complete introduction of the β-rhodinose in the
natural series, conditions were needed for the diastere-
oselective reduction of (+)-25a. Fortunately an efficient
solution was found in a protocol developed by Deng,
wherein simple substitution of Ru with Rh in a typical
Noyori transfer hydrogenation allows for catalyst con-
trolled reduction of enones to their respective saturated
alcohols.25 Applying the latter conditions to (+)-25a
resulted in smooth conversion to (+)-26 which, upon
deprotection and oxidation furnishes p-quinol (-)-27
Our ability to readily access (±)-6 (12 steps, 12%
overall yield) coupled with the availability of both (+)-
and (-)-24 prompted investigations into the preparation
of enantiomeric tetrapetalone A (i.e. (+)-1). As illustrat-
ed in Scheme 4 simple hydrolysis of (-)-25b followed by
glycosylation of the derived aglycone ((-)-6) with (-)-24
set the stage for catalyst controlled diasteroselective re-
duction to (-)-26 (not depicted). Advancement of (-)-26
in a manner identical to that employed for (+)-26
(Scheme 3) then furnished (+)-1.
,
(10% yield, three steps).26 27 At this stage all that re-
mained to complete the synthesis of (-)-1 was unmask-
ing of the tetramic acid moiety, a maneuver that was
readily achieved by exposure of (-)-27 to LiOMe (86%
yield).28
With the hope of eventually preparing the entire fami-
ly of tetrapetalones, we next turned to the preparation of
tetrapetalone C. To this end, our ability to cleave the
exo-methylene in 20, without affecting the trisubstituted
azepine olefin, by using DMDO as an oxidant (Scheme
2) prompted us to consider this reagent in the conversion
of tetrapetalone A to C. In the event we were pleased to
observe that brief exposure of (+)- or (-)-1 to DMDO
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followed by evaporation of the solvent furnished (+)- or
Page 4 of 6
1
2
3
4
5
6
7
8
(-)-tetrapetalone C (3), respectively, in excellent yield
and characterizable purity.30
Scheme 4. Oxidation of tetrapetalone A to
tetrapetalone C
N.; Sugiyama, Y.; Imachi, M.; Hirota, H.; Koshino, H.; Hirota, A.
Biosci. Biotechnol. Biochem. 2004, 68, 104-111.
2 (a) Komoda, T.; Kishi, M.; Abe, N.; Sugiyama, Y.; Hirota, A. Bi-
osci. Biotechnol. Biochem. 2004, 68, 903-908; (b) Komoda, T.;
Sugiyama, Y.; Hirota, A. Org. Biomol. Chem. 2007, 5, 1615-1620.
H
H
Et
Et
OH
O
OH
N
OH
N
DMDO
OH
O
O
O
O
3
Komoda, T.; Akasaka, K.; Hirota, A. Biosci. Biotechnol. Bio-
O
O
HO
HO
9
chem. 2008, 72, 2392-2397.
O
O
4 For Sarpong’s original report, see: (a) Marcus, A. P.; Sarpong, R.
Org. Lett. 2010, 12, 4560-4563; A later stereochemical revision found
that the prepared advanced intermediate indeed possessed the correct
stereochemical configuration about the 5-carbon ring, see: (b) Mar-
cus, A. P.; Sarpong, R. Org. Lett., 2014, 16, 3420; Earlier studies in
utilizing a Nazarov reaction to build the AB ring system were detailed
in earlier work, see: (c) Marcus, A. P.; Lee, A. S.; Davis, R. L.; Tan-
tillo, D. J.; Sarpong, R. Angew. Chem. Int. Ed. 2008, 47, 6379-6383.
10
11
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(+)- or (-)-tetrapetalone A (1)
(>90% yield)
(+)- or (-)-tetrapetalone C (3)
In conclusion, we have herein outlined an efficient
stereocontrolled preparation of a tetrapetalone aglycone
scaffold (6) that upon further manipulation provides ac-
cess to synthetic (-)- and (+)- tetrapetalones A and C in
18- and 19-steps, respectively. Current efforts are being
directed toward preparing tetrapetalones B/D and studies
into alternative methods for accessing the p-quinol
moiety. The results of these efforts will be described in
due course.
5
For Porco’s original report, see: (a) Wang, X.; Porco, J. A. An-
gew. Chem. Int. Ed. 2005, 44, 3067-3071; The assignment of a late
stage intermediate in this report has since been reassigned. For correc-
tion, see: (b) Wang, X.; Porco, J. A. Angew. Chem. Int. Ed. 2006, 45,
6607.
6
David, J. G.; Bai,W.-J.; Weaver, M. G.; Pettus, T. R. R. Org.
Lett., 2014, 16, 4384-4387.
ASSOCIATED CONTENT
7 Li, C.; Li, X.; Hong, R. Org. Lett., 2009, 11, 4036-4039.
8
Supporting Information.
The Supporting Information is available free of charge on
the ACS Publications website.
For completion of the synthesis of tetrapetalone A-Me aglycone
see: (a) Carlsen, P. N.; Mann, T. J.; Hoveyda, A. H.; Frontier, A. J.
Angew. Chem. Int. Ed. 2014, 53, 9334-9338; For studies toward the
AB ring system of tetrapetalone A, see: (b) Carlsen, P. N.; Jiang, C.;
Herrick, I. R.; Frontier, A. J. Tetrahedron 2015, 71, 5886-5896.
Experimental procedures, spectroscopic data and copies of
NMR spectra (PDF)
X-Ray structure for ent-20 (CIF)
9
(a) Howell, J. M., Ph.D. Dissertation, Colorado State University,
Fort Collins, CO, 2012; (b) McMahon, T. C., Ph.D. Dissertation,
Colorado State University, Fort Collins, CO, 2013.
10 Dhanjee, H. H.; Haley, M. W.; McMahon, T. C.; Buergler, J. F.;
Howell, J. M.; Kobayashi, Y.; Fujiwara, K.; Wood, J. L. Tetrahedron
Lett. 2016, 72, 3673-3677.
AUTHOR INFORMATION
Corresponding Author
11 It was found that 4 Å M.S. are a crucial additive to prevent dele-
terious side reactions with the methanol byproduct.
*john_l_wood@baylor.edu
12
Maruoka, K.; Imoto, H.; Saito, S.; Yamamoto, H. J. Am. Chem.
Funding Sources
Soc. 1994, 116, 4131-4132.
13
CPRIT (R1309)
Welch Foundation (Chair AA-006)
Notes
Attempts to promote an enantioselective conjugate addition of
the silyl-enol ether derived from 9 utilizing pyrrolidine derived or-
ganocatalysts failed to provide any of the desired conjugate addition
product.
No competing financial interests have been declared.
14
(a) Motiwala, H. F.; Vekariya, R. H.; Aubé, J. Org. Lett. 2015,
17, 5484-5487; (b) Corby, B. W.; Smyth, T. P. J. Org. Chem. 1998,
63, 8946-8951. (c) On multigram scale standard Lewis Acid promot-
ed conditions were employed and effected ring closure in 60-70%
yields. On these scales, the subsequent elimination (DBU) proceeds
in 89% yield (see supporting information).
ACKNOWLEDGMENTS
The authors thank Prof. Kevin Klausmeyer and Ms. Sam
Yruegas for obtaining and analyzing X-ray crystallographic
data. We also gratefully acknowledge financial support
from Baylor University, the Welch Foundation (Chair, AA-
006), and the Cancer Prevention and Research Institute of
Texas (CPRIT, R1309).
15
It should be noted that intermediates 13, 9, 16 and 7 are pro-
duced as inconsequential mixtures of diastereomers. For ease of
analysis, the major diastereomer of 7 (illustrated) was separated and
employed in developing the synthesis.
16
(a) Shan, G.; Yang, X.; Ma, L.; Rao, Y. Angew. Chem. Int. Ed.
2012, 51, 13070-13074; (b) Mo, F.; Trzepkowski, L. J.; Dong, G.
Angew. Chem. Int. Ed. 2012, 51, 13075-13079; (c) Mo, F.; Trzepkow-
ski, L. J.; Dong, G. Angew. Chem. Int. Ed. 2013, 52, 5425.
REFERENCES
17
The mechanism of this reaction has yet to be fully delineated.
Evidence of a cylcoadditon pathway was revealed by the isolation of
SI-2 in 10% yield (see supporting information).
H
Et
1(a) Komoda, T.; Sugiyama, Y.; Abe, N.; Imachi, M.; Hirota, H.;
Hirota, A. Tetrahedron Lett. 2003, 44, 1659-1661; (b) Komoda, T.;
Sugiyama, Y.; Abe, N.; Imachi, M.; Hirota, H.; Hirota, A. Tetrahe-
dron Lett. 2003, 44, 7417-7419; (c) Komoda, T.; Yoshida, K.; Abe,
TMS
O
O
N
CO2Et
O
OTIPS
SIꢀ2
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2
3
4
5
6
7
8
9
18
rivatives see: (b) Song, W.; Zhao, Y.; Lunch, J. C.; Kim, H.; Tang, W.
For a simple preparation of DMDO, see: Taber, D.; DeMatteo,
Chem. Commun. 2015, 51, 17475-17478.
P. W.; Hassan, R. A. Org. Synth. 2013, 90, 350-357.
26
19
To our knowledge, the use of hypervalent iodine and t-BuOOH
For in situ epoxide hydrolysis and cleavage to produce benzylic
in oxidative dearomatizations was first reported by Pettus, see (a)
Feng, Z.-G.; Bai, W.-J.; Pettus, T. R. R. Angew. Chem. Int. Ed. 2015,
54, 1864-1867; For the development of the conditions employed by
Frontier, see: (b) Ratnikov, M. O.; Farkas, L. E.; McLaughlin, E. C.;
Chiou, G.; Choi, H.; El-Khalafy, S. H.; Doyle, M. P. J. Org. Chem.
2011, 76, 2585-2593; For Frontier’s original report see Reference 8a;
The hypervalent iodine procedure proved to be comparable to its
metal catalyzed counterpart but was employed here due to shorter
reactions times (~15 minutes verus 3 h).
ketones, see: Binder, C. M.; Dixon, D. D.; Almaraz, E.; Tius, M.;
Singaram, B. Tetrahedron Lett. 2008, 49, 2764-2767.
20
The use of Luche conditions was prompted by observations
made during the reduction of enone 7 which, when performed in the
abscence of cerium additives, proceeds via competing reduction of
both ketones.
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26
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21
Attempts to glycosylate 6, using BF3•OEt2 in combination with a
fully functionalized glycosyl donor containing an anomeric acetate,
furnished exslusiely the α-anomer as evidenced by 1H-NMR analysis.
22 (a) Babu, R. S.; O’Doherty, G. A. J. Am. Chem. Soc. 2003, 125,
12406-12407; For an example and preparation of β-D-Boc-pyranone
specifically, see: (b) Zhou, M.; O’Doherty, G. A. Org. Lett. 2006, 8,
4339-4342.
27
Although NMR data on crude reaction mixtures prior to Pb/Cd
reduction indicated the presence of diastereomers, (-)-27 was the sole
isomer isolated from the reaction mixture. In addition, a 25% yield of
phenol (e.g. desilylated (+)-26) was recovered along with side prod-
ucts attributable to o-quinone formation (see supporting information).
23
Bajaj, S. O.; Farnsworth, J. R.; O’Doherty, G. A. Org. Synth.
28
Exploration of saponification conditions employing LiOH on
2014, 91, 338-355.
24
substrates lacking the rhodinose revealed the tendency of these condi-
tions to promote a retro-Dieckmann reaction.
In an attempt to effect the kinetic resolution of (±)-6 the glyco-
sylation was performed with 0.5 equivalents of donor (+)-24. Unfor-
tunately, NMR and LCMS analysis showed a 1:1.7 d.r. of 25a:25b
thus favoring the undesired diastereomer.
29
To the best of our knowledge, no optical rotation data is availa-
ble for any member of the tetrapetalone family. The absolute stereo-
chemistry of the synthetic material was assigned based upon Mosher
ester analysis of (-)-6 and known absolute configuration of 24 (see
Ref. 21).
25 (a) Li, X.; Li, L.; Tang, Y.; Zhong, L.; Cun, L.; Zhu, J.; Liao, J.;
Deng, J. J. Org. Chem. 2010, 75, 2981-2988; For the applications of
Deng’s protocol (ref 25a) in the preparation of simple rhodinose de-
30
For hydroxylation reactions employing DMDO, see: Adam, W.;
Smerz, A. K. Tetrahedron 1996, 52, 5799-5804.
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