Total synthesis of spirastrellolide A methyl ester - Part 1: Synthesis of an advanced C17-C40 bis-spiroacetal subunit

Article abstract of DOI:10.1002/anie.200705565

Out of the blue: The marine macrolide spirastrellolide A is a potent and selective inhibitor of protein phosphatase 2A and a lead for anticancer therapies. A flexible and modular synthetic strategy has been developed with two routes for the construction o

Full text of DOI:10.1002/anie.200705565

Communications
DOI: 10.1002/anie.200705565
Natural Product Synthesis
Total Synthesis of Spirastrellolide A Methyl Ester—Part 1: Synthesis of
an Advanced C17–C40 Bis-spiroacetal Subunit**
Ian Paterson,* Edward A. Anderson, Stephen M. Dalby, Jong Ho Lim, Julien Genovino,
Philip Maltas, and Christian Moessner
Spirastrellolide A (1, Scheme 1) and its methyl ester deriva-
tive 2 were isolated in 2003 by Andersen and co-workers from
the Caribbean marine sponge Spirastrella coccinea.[1] The
spirastrellolides are potent, highly selective inhibitors of
protein phosphatase 2A (IC50 = 1 nm for 1), causingprema-
ture cell entry into mitosis.[1b] Protein phosphatases play a
vital role in the regulation of many cellular processes,
interference of which has been implicated in the onset of
[2]
several diseases includingcancer and Alzheimerꢀs.
There-
fore, the identification of selective inhibitors of protein
phosphatases may afford both valuable molecular probes
for cell biology, as well as promising lead compounds for the
development of novel therapeutic agents.[3]
From a structural perspective, spirastrellolide A consists
of a 47-carbon backbone with 21 stereocenters, of which 20
are included within a 38-membered macrocycle that also
comprises three cyclic ether subunits (A, BC, and DEF rings).
The intriguing structure (Scheme 1), coupled with the potent
biological profile, has inspired us[4] and other research
groups[5] to initiate studies towards a total synthesis. Herein
we report the stereocontrolled synthesis of the advanced C17–
C40 bis-spiroacetal subunit 3, by followingtwo complemen-
tary routes that are based on different fragment-coupling
strategies. In the accompanying communication, we report its
elaboration to incorporate the BC spiroacetal domain, and
the subsequent macrocyclization and attachment of the side
chain, which has culminated in the first total synthesis of
spirastrellolide A methyl ester.
At the outset of our work, the relative and absolute
configuration of spirastrellolide A was undefined.[1a] Despite
extensive NMR studies,[1b] the relative stereochemistry
between four principle regions of the molecule (C3–C7, C9–
C24, C27–C38, and the remote C46 stereocenter) remained
unknown. Only in 2007 was the structural ambiguity resolved,
with the isolation of spirastrellolide B (lackingboth the
chlorine substituent at C28 and the C15–C16 alkene), and the
X-ray crystal structure of a derivative,[1c] followed by the
assignment at C46 through chemical degradation studies.[1d]
As outlined in Scheme 2, we envisaged a late-stage
attachment of the side chain by employingstannane 4 (or
its enantiomer), after macrolactonization of an appropriate
seco acid 5. The next key disconnection involves unraveling
the BC ringspiroacetal, and implementation of an alkyne
addition/Lindlar reduction sequence usingthe alkyne 6, a
tactic that had proven robust in earlier studies.[4b,c,e] In
contrast, the scission of the pivotal C17–C40 fragment into
two stereochemically discrete subunits was uncharted terri-
tory, and led us to explore two alternative strategies. In
Strategy A, a disconnection between C25 and C26 in 7 was
envisaged by using a modified Julia olefination[6] between
sulfone 8 and aldehyde 9, the latter beingdirectly available
from our previous work.[4d] This strategy benefits from the
installation of the required C20–C24 stereopentad before
olefination, and provides a fully functionalized C17–C40
subunit 7. The choice of a C40 benzyl ether in 7 would enable
rapid assessment of the validity of this approach, as this
Scheme 1. Spirastrellolide A (1), its methyl ester (2), and the advanced
C17–C40 subunit 3. PMB=para-methoxybenzyl, TBS=tert-butyldime-
thylsilyl, TES=triethylsilyl.
[*] Prof. Dr. I. Paterson, Dr. E. A. Anderson, S. M. Dalby, J. H. Lim,
J. Genovino, P. Maltas, Dr. C. Moessner
University Chemical Laboratory
University of Cambridge
Lensfield Road, Cambridge, CB2 1EW (UK)
Fax: (+44)1223-336-362
E-mail: ip100@cam.ac.uk
Homepage: http://www-paterson.ch.cam.ac.uk
[**] This work was supported by the EPSRC (GR/C541677/1), Merck
Research Laboratories, Homerton College, Cambridge (E.A.A.), SK
Corporation (J.H.L.), and the German Academic Exchange Service
(C.M.). We thank Prof. R. J. Andersen (University of British
Columbia) for helpful discussions.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
3016
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2008, 47, 3016 –3020

Angewandte
Chemie
Scheme 2. Retrosynthetic analysis of spirastrellolide A methyl ester (2) based on Julia (Strategy A) and Suzuki (Strategy B) fragment coupling
reactions to construct the pivotal C17–C40 subunit. Bn=benzyl, BT=benzothiazole, PG=protecting group.
protectinggroup is already present in aldehyde 9. Never-
theless, in anticipation of the challenges we might face with
such a hindered olefination, we also contemplated Strategy B,
d.r. 95:5). Followingformation of the methyl ether ( 20), a
sequence involvingacetal cleavaeg, persilylation of the
resultingtriol with TESOTf, and selective desilylation gave
the primary alcohol 21 (71%). Completion of the targeted
sulfone 8 required introduction of the benzothiazolylsulfone
functionality, which was achieved from 21 by sulfide forma-
tion under Mitsunobu conditions and oxidation with
[(NH4)6Mo7O24] (69%, over 2 steps). Overall, the C17–C25
sulfone 8 was prepared in 16 steps and 6.4% yield from ester
12.
The C26–C40 DEF bis-spiroacetal aldehyde 9 could be
readily prepared from the acyclic diene 22 by usingour
tandem double-Sharpless asymmetric dihydroxylation/spiro-
cyclization tactic (Scheme 4).[4d] Takinginto consideration the
need for scale-up, we improved the route towards diene 22.
This commenced with the Oehlschlager–Brown chloroallyl-
ation[12] of aldehyde 23[13] (with in situ acetal cleavage), and
subsequent methyl ether formation, to give the ketone 24
(d.r. > 95:5, 92% ee) with installation of the C28 and C29
stereocenters. Addition of the dicyclohexylboron enolate of
24 (cHex2BCl, Et3N) to aldehyde 25[4d] gave a mixture of
epimeric aldol adducts which underwent clean elimination
(MsCl, Et3N). This robust sequence enabled the rapid and
facile preparation of triene 26 on a 10-gscale. The elaboration
of 26 to the targeted tricyclic DEF subunit was accomplished
by a four-step sequence of enone/ketone reduction,[14] silyl
ether cleavage, and Swern oxidation of the resulting diol to
afford diene 22 (68%).[15] By followingour previous route, [4d]
22 underwent efficient double Sharpless asymmetric dihy-
droxylation[16]/cyclization to afford the C26–C40 DEF bis-
À
in which the C24 C25 bond would be forged using an
[7]
ambitious sp2–sp3 Suzuki cross-couplingreaction involving
the C17–C24 iodide subunit 10 and alkene 11. A subsequent
double hydroboration of the resultingdiene might then install
the requisite stereocenters at C23 and C24 as well as
oxygenation at C17 and C23, thus enabling conversion into
the required aldehyde functionality in 3. In practice, we
elected to pursue both these strategies, mindful also of the
potential benefits of structural correlation of advanced
intermediates common to both routes.
Strategy A commenced with synthesis of the C17–C25
sulfone 8 (Scheme 3). Based on the work of Seebach and
Warmuth[8a] and others[8b,9] the chelated lithium enolate of the
methyl ester 12 of (S)-malic acid was methylated to afford 13
(d.r. 90:10),[8] followed by transformation into the aldehyde
14[9] in readiness for an Evans glycolate aldol coupling
reaction. As our BC-spiroacetalization strategy called for a
PMB ether at C21, this required the use of the imide 15.[10]
Pleasingly, reaction of the (Z)-dibutylboron enolate of 15 with
aldehyde 14 in toluene provided the syn-aldol adduct 16, thus
installingthe C21 and C22 stereocenters (76%, d.r. 95:5).
Assembly of the full C20–C24 stereopentad was completed
followingthe stepwise conversion of 16 into the ketone 17
through addition of allylmagnesium bromide to the inter-
mediate Weinreb amide 18.[11] Treatment of 17 with zinc
borohydride (diethyl ether, À108C) effected a chelation-
controlled reduction to afford the C20 alcohol 19 (78%,
Angew. Chem. Int. Ed. 2008, 47, 3016 –3020
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3017

Communications
=
Scheme 4. Improved route to form the C26–C40 aldehyde 9. a) CH2
CHCH2Cl, cHex2NLi, (À)-Ipc2BOMe, THF, Et2O, À958C; BF3·Et2O; 23,
À958C to À788C; 30% H2O2, pH 7 buffer; b) Me3OBF4, proton
sponge, CH2Cl2, 08C, 39% (over 2 steps); c) cHex2BCl, Me2NEt, Et2O,
08C; 25, À788C, 88%; d) MsCl, Et3N, 08C to RT, 83%;
e) [{(Ph3P)CuH}6], PhSiH3, toluene, 90%; f) DIBALH, CH2Cl2, À788C;
g) 1n HCl, MeCN, RT; h) DMSO, (COCl)2, Et3N, CH2Cl2, À788C to
08C, 75% (over 3 steps); i) see Ref. [4d], 65%; j) PPTS, CH2Cl2/
MeOH (6:1), 08C; DMP, NaHCO3, CH2Cl2, 78%. cHex=cyclohexyl,
DIBALH=diisobutylaluminum hydride, DMSO=dimethyl sulfoxide,
Ipc=isopinocampheyl, Ms=methanesulfonyl, PPTS=pyridinium para-
toluenesulfonate.
Scheme 3. Preparation of the C17–C25 sulfone 8. a) LDA, THF, HMPA,
À788C to RT, 61%; b) LiAlH4, THF, RT; PhCH(OMe)2, TsOH, CH2Cl2,
Et3N, RT; DMP, CH2Cl2, RT, 53% (over 3 steps); c) 15, nBu2BOTf,
Et3N, toluene, À508C; 14, À508C to À308C, 76% (d.r. 95:5);
d) AlMe3, MeNH(OMe)·HCl, THF, À208C to RT; TESOTf, 2,6-lutidine,
=
CH2Cl2, 72%; e) CH2 CHCH2MgBr, THF, À208C, 95%; f) Zn(BH4)2,
Et2O, À108C, 78%; g) Me3OBF4, proton sponge, CH2Cl2, 94%;
h) TsOH, MeOH, 94%; i) TESOTf, 2,6-lutidine, CH2Cl2, 08C, 100%;
j) HF·Py/Py (1:3), THF, 08C to RT, 80%; k) BTSH, PPh3, DEAD, THF,
99%; l) [(NH4)6Mo7O24], 30% H2O2, EtOH, RT, 70%. BTSH=2-
mercaptobenzothiazole, DEAD=diethylazodicarboxylate, DMP=Dess–
Martin periodinane, LDA=lithium diisopropylamide, HMPA=hexa-
methyl phosphoramide, PMB=para-methoxybenzyl, proton
sponge=1,8-bis(dimethylamino)naphthalene, Py=pyridine, Tf=tri-
fluoromethanesulfonyl, Ts=para-toluenesulfonyl.
clear that Strategy A had not performed to our expectations,
not least because of the rather lengthy synthesis of the sulfone
8 and the disappointingyield of the key fragment coupling
step, presumably as a result of steric hindrance imposed by
the bis-spiroacetal for reaction at the C26 position of
aldehyde 9.
We next turned to Strategy B (Scheme 2), involving an
ambitious sp2–sp3 Suzuki couplingreaction to assemble the
C17–C40 aldehyde 3. This alternative route would benefit
spiroacetal 27 (65%). After selective cleavage of the C26 TES
ether, 27 was converted into the aldehyde 9[5i] by usingDess–
Martin periodinane.
À
À
from movingthe key bond scission from C25 C26 to C24
C25, thus potentially counteractingthe perceived steric
encumbrance that had plagued the Julia coupling approach.
At this point, the protectinggroup at C40 was switched to a
TBS ether, which should be more easily cleaved in the
With a scalable route to the aldehyde 9 established, the
feasibility of the Julia-type couplingin Strategy A could now
be explored (Scheme 5). After extensive experimentation, we
found that generation of the lithium anion of sulfone 8
(LHMDS, À788C, THF) followed by the addition of aldehyde
9 and warmingthe reaction to ambient temperature afforded
the C17–C40 alkene 28 in 32% yield. Despite the modest
yield, Strategy A was validated by selective hydroboration of
the terminal olefin to give the primary alcohol, followed by
reduction of the internal double bond with diimide to afford
29 (81%, over 2 steps). Finally, Dess–Martin oxidation of 29
delivered the C17–C40 aldehyde 7 (84%), which was primed
to undergo coupling with the C1–C16 alkyne 6 and complete
the assembly of the C1–C40 framework. Nevertheless, it was
À
presence of the C15 C16 dpuble bond compared to cleavage
of a benzyl ether. Preparation of the C25–C40 alkene 11
(Scheme 6) began from the C26–C40 intermediate 27[4d] by
debenzylation, formation of the TBS ether, and selective
manipulations at C26 (cleavage of the TES ether, oxidation to
the aldehyde, and Wittigmethylenation). This sequence
provided the alkene 11, destined for a Suzuki cross-coupling
reaction, on a multigram scale (46% from 27). Similar
quantities of the vinyl iodide partner 10 could be prepared
startingfrom the aldehyde 30[17] by usingan Evans glycolate
aldol reaction analogous to that employed for sulfone 8.[10]
3018
www.angewandte.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2008, 47, 3016 –3020

Angewandte
Chemie
Weinreb amide[11] yielded ketone 32 (80%). The remaining
C20 stereocenter was established as before by usinga
chelation-controlled reduction of 32 with zinc borohydride
(d.r. > 95:5), and two further steps provided the desired vinyl
iodide 10 (83%). Notably, this sequence represents a
substantial improvement over the earlier synthesis of sulfone
8, as it is accomplished in just six steps from aldehyde 30 (52%
yield).
We were now faced with the challenging union of the
complex subunits 10 and 11 (Scheme 7). Gratifyingly, hydro-
boration of the alkene 11 by using9-BBN, followed by
addition of the iodide 10 and a catalytic amount of [PdCl2-
(dppf)], led to a smooth sp2–sp3 Suzuki couplingreaction and
formation of the trisubstituted (23E)-alkene 33 in 83%
yield.[18] The completion of the targeted C17–C40 subunit 3
required the installation of stereocenters at C23 and C24, for
which we planned to use a substrate-controlled hydrobora-
tion. Although such hydroborations have good precedence
[19]
for delivering1,3-diols from other allylic alcohol systems,
this particular alkene substitution pattern has not been used
to afford 1,2-diols, and therefore the stereochemical outcome
Scheme 5. Modified Julia olefination to form the C17–C40 subunit 7.
a) 8, LHMDS, THF, À788C; 9, À788C to RT, 32%; b) BH3·SMe2, THF,
08C; 30% H2O2, pH 7 buffer; c) (NCO2K)2, AcOH, Py, MeOH, 81%
(over 2 steps); d) DMP, NaHCO3, CH2Cl2, 84%. LHMDS=lithium
hexamethyldisilazide.
Scheme 6. Preparation of the C25–C40 alkene 11 and the C17–C24
vinyl iodide 10. a) H2, Raney-Ni, EtOH; TBSCl, imidazole, CH2Cl2,
86%; b) PPTS, CH2Cl2/MeOH (7:1), 08C; c) DMP, NaHCO3, CH2Cl2;
=
d) Ph3P CH2, THF, À788C to RT, 53% (over 3 steps); e) nBu2BOTf,
Et3N, toluene, À508C; 30, À508C to À308C, 79% (d.r. 95:5); f) AlMe3,
MeNH(OMe)·HCl, THF, À208C to RT; TESOTf, 2,6-lutidine, CH2Cl2,
=
À788C, 86%; g) CH2 CHCH2MgBr, THF, À788C to 08C, 93%; h) Zn-
Scheme 7. Suzuki coupling reaction of alkene 11 and iodide 10:
formation of the fully functionalized C17–C40 aldehyde 3. a) 9-BBN,
THF; H2O; 10, [PdCl2(dppf)], Ph3As, Cs2CO3, THF/DMF (1:1), 83%;
b) BH3·SMe2, THF; MeOH, 30% H2O2, 1m NaOH, 08C to RT;
c) TESOTf, 2,6-lutidine, CH2Cl2, À788C, 67% (over 2 steps, d.r. 75:25);
d) PPTS, CH2Cl2/MeOH (12:1), 08C, 98%; e) DMP, NaHCO3, CH2Cl2,
80%. 9-BBN=9-borabicyclo[3.3.1]nonane, DMF=N,N-dimethylform-
amide, dppf=1,1’-bis(diphenylphosphanyl)ferrocene.
(BH4)2, Et2O, À508C, 90% (d.r. >95:5); i) Me3OBF4, proton sponge,
CH2Cl2, 93%; j) PPTS, MeOH, 99%.
Once again, this reaction selectively installed the required
C21 and C22 stereocenters (79%, d.r. 95:5). Subsequent
cleavage of the auxiliary, and allylation of the intermediate
Angew. Chem. Int. Ed. 2008, 47, 3016 –3020
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3019

Communications
g) A. B. Smith III, D.-S. Kim, Org. Lett. 2007, 9, 3311; h) C.
Wang, C. J. Forsyth, Heterocycles 2007, 72, 621; i) A. Fꢁrstner, B.
Fasching, G. W. OꢀNeil, M. D. B. Fenster, D. Godbout, L.
Ceccon, Chem. Commun. 2007, 3045.
was uncertain. In the event, we found the double hydro-
boration reaction required an unprotected alcohol at C22, and
that this substrate 33 gave a 3:1 ratio of diastereomers (which
proved difficult to separate) in favor of the desired C22,C23-
anti isomer 34. Configurational assignment was performed on
a closely related system[20] by chemical correlation with
intermediate 29 (Scheme 5), NOE studies of a derivative,[21]
and was confirmed by an X-ray crystal structure of a more
advanced intermediate.[22] Finally, aldehyde 3 was attained by
silylation of the crude triol 34 to give 35, followed by selective
cleavage of the TES ether at C17 to generate the alcohol 36
and Dess–Martin oxidation (44%, over 4 steps from 11).
Overall, this expedient Suzuki/hydroboration route is clearly
superior to the alternative Julia olefination sequence
(Scheme 5) and, importantly, proved readily amenable to
providinggram quantities of aldehyde 3.[23]
In conclusion, we have completed the stereocontrolled
preparation of the fully functionalized C17–C40 DEF bis-
spiroacetal subunits 7 and 3, by usingindependent Julia and
Suzuki couplingstrateiges, respectively. The scalable and
efficient synthesis of aldehyde 3 forms the cornerstone of our
campaign towards the total synthesis of spirastrellolide A
methyl ester, which is reported in the followingcommunica-
tion.[22]
[6] a) P. R. Blakemore, J. Chem. Soc. Perkin Trans. 1 2002, 2563;
b) J. B. Baudin, G. Hareau, S. A. Julia, O. Ruel, Tetrahedron Lett.
1991, 32, 1175.
[7] a) N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457; b) S. R.
Chemler, D. Trauner, S. J. Danishefsky, Angew. Chem. 2001, 113,
4676; Angew. Chem. Int. Ed. 2001, 40, 4544; c) K. C. Nicolaou,
P. G. Bulger, D. Sarlah, Angew. Chem. 2005, 117, 4516; Angew.
Chem. Int. Ed. 2005, 44, 4442.
[8] a) D. Seebach, D. Wasmuth, Helv. Chim. Acta 1980, 63, 197;
b) G. Frꢂter, Helv. Chim. Acta 1979, 62, 2825; c) A. J. F.
Edmunds, W. Trueb, W. Oppolzer, P. Cowley, Tetrahedron
1997, 53, 2785.
[9] R. W. Hoffmann, G. Mas, T. Brandl, Eur. J. Org. Chem. 2002,
3455.
[10] a) T. K. Jones, S. G. Mills, R. A. Reamer, D. Askin, R. Desmond,
R. P. Volante, I. Shinkai, J. Am. Chem. Soc. 1989, 111, 1157;
b) D. A. Evans, J. R. Gage, J. L. Leighton, A. S. Kim, J. Org.
Chem. 1992, 57, 1961.
[11] J. I. Levin, E. Turos, S. M. Weinreb, Synth. Commun. 1982, 12,
989.
[12] S. Hu, S. Jayaraman, A. C. Oehlschlager, J. Org. Chem. 1996, 61,
7513.
[13] I. Paterson, M. E. Di Francesco, T. Kꢁhn, Org. Lett. 2003, 5, 599.
[14] B. H. Lipshutz, J. Keith, P. Papa, R. Vivian, Tetrahedron Lett.
1998, 39, 4627.
[15] Direct deprotection/oxidation of the C35 silyl ether of the
ketone resulting from conjugate reduction led to significant
quantities of a dihydropyran by-product, which resulted from
dehydration of an intermediate hemiacetal.
[16] H. C. Kolb, M. S. VanNieuwenhze, K. B. Sharpless, Chem. Rev.
1994, 94, 2483.
[17] Aldehyde 31 was prepared by Dess–Martin oxidation (84%) of
the correspondingalcohol, itself available throuhg titanium-
catalyzed hydromagnesiation/iodination of butyn-2-ol, see F.
Sato, Y. Kobayashi, Org. Synth. 1990, 690, 106.
[18] C. R. Harris, S. D. Kuduk, A. Balog, K. Savin, P. W. Glunz, S. J.
Danishefsky, J. Am. Chem. Soc. 1999, 121, 7050.
[19] a) W. C. Still, J. C. Barrish, J. Am. Chem. Soc. 1983, 105, 2487 –
2489. For a recent example, see b) I. Paterson, A. D. Findlay,
E. A. Anderson, Angew. Chem. 2007, 119, 6819; Angew. Chem.
Int. Ed. 2007, 46, 6699.
[20] The C40 benzyl ether analogue of diene 33 gave a similar
mixture of triols upon hydroboration, the 1H NMR spectra of
which correlated closely with that of 34. The triols were
converted into intermediate 29 (Scheme 5) by persilylation
(TESOTf) and selective C17 deprotection, thus confirmingthe
configurations at C23 and C24.
Received: December 5, 2007
Published online: February 28, 2008
Keywords: antitumor agents · enzyme inhibitors · macrolides ·
.
spiroacetals · total synthesis
[1] a) D. E. Williams, M. Roberge, R. Van Soest, R. J. Andersen, J.
Am. Chem. Soc. 2003, 125, 5296; b) D. E. Williams, M. Lapawa,
X. Feng, T. Tarling, M. Roberge, R. J. Andersen, Org. Lett. 2004,
6, 2607; c) K. Warabi, D. E. Williams, B. O. Patrick, M. Roberge,
R. J. Andersen, J. Am. Chem. Soc. 2007, 129, 508; d) D. E.
Williams, R. A. Keyzers, K. Warabi, K. Desjardine, J. L. Riffell,
M. Roberge, R. J. Andersen, J. Org. Chem. 2007, 72, 9842.
[2] a) R. E. Honkane, T. Golden, Curr. Med. Chem. 2002, 9, 2055;
b) V. Janssens, J. Goris, Biochem. J. 2001, 353, 417.
[3] a) D. J. Newmann, G. M. Cragg, J. Nat. Prod. 2007, 70, 461; b) I.
Paterson, E. A. Anderson, Science 2005, 310, 451; c) F. E.
Koehn, G. T. Carter, Nat. Rev. Drug Discovery 2005, 4, 206;
d) I. Paterson, K.-S. Yeung, Chem. Rev. 2005, 105, 4237.
[4] a) I. Paterson, E. A. Anderson, S. M. Dalby, O. Loiseleur, Org.
Lett. 2005, 7, 4121; b) I. Paterson, E. A. Anderson, S. M. Dalby,
O. Loiseleur, Org. Lett. 2005, 7, 4125; c) I. Paterson, E. A.
Anderson, S. M. Dalby, Synthesis 2005, 3225; d) I. Paterson,
E. A. Anderson, S. M. Dalby, J. H. Lim, P. Maltas, C. Moessner,
Chem. Commun. 2006, 4186; e) I. Paterson, E. A. Anderson,
S. M. Dalby, J. Genovino, J. H. Lim, C. Moessner, Chem.
Commun. 2007, 1852; f) I. Paterson, E. A. Anderson, S. M.
Dalby, J. H. Lim, O. Loiseleur, P. Maltas, C. Moessner, Pure
Appl. Chem. 2007, 79, 667.
[21] The major triol formed in the correspondingbenzyl ether series
was also converted into the cis-carbonate 37.
[5] a) J. Liu, R. P. Hsung, Org. Lett. 2005, 7, 2273; b) Y. Pan, J. K.
De Brabander, Synlett 2006, 853; c) C. Wang, C. J. Forsyth, Org.
Lett. 2006, 8, 2997; d) A. Fꢁrstner, M. D. B. Fenster, B. Fasching,
C. Godbout, K. Radkowski, Angew. Chem. 2006, 118, 5632;
Angew. Chem. Int. Ed. 2006, 45, 5506; e) A. Fꢁrstner, M. D. B.
Fenster, B. Fasching, C. Godbout, K. Radkowski, Angew. Chem.
2006, 118, 5636; Angew. Chem. Int. Ed. 2006, 45, 5510; f) J. Liu,
J. H. Yang, C. Ko, R. P. Hsung, Tetrahedron Lett. 2006, 47, 6121;
[22] I. Paterson, E. A. Anderson, S. M. Dalby, J. H. Lim, J. Genovino,
P. Maltas, C. Moessner, Angew. Chem. 2008, DOI: 10.1002/
ange.200705566; Angew. Chem. Int. Ed. 2008, DOI: 10.1002/
anie.200705566.
[23] See the SupportingInformation.
3020 www.angewandte.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2008, 47, 3016 –3020