October 1998
SYNLETT
1091
Anomeric Oxygen to Carbon Rearrangements of Alkynyl Tributylstannane Derivatives of
Lactols.
Marianne F. Buffet, Darren J. Dixon, Steven V. Ley* and Edward W. Tate.
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, U.K.
Received 17 July 1998
Abstract: Treatment of alkynyl tributylstannane tetrahydropyranyl and
tetrahydrofuranyl ether derivatives with boron trifluoride etherate effects
an efficient anomeric oxygen to carbon rearrangement leading to the
corresponding carbon-linked alkynol products.
The overwhelming abundance of naturally occurring products
containing carbon-linked tetrahydropyranyl and tetrahydrofuranyl
Scheme 3
heterocycles has inspired the development of methodology for their
synthesis, especially over the past two decades.
1
In a recent communication we have described a new route to 2-alkyl
substituted pyran derivatives starting from readily prepared
tetrahydropyranyl ether derivatives of a variety of alkenols, under mild
In further studies we investigated the rearrangement of 6-substituted
tetrahydropyranyl ether derivative 11. The alkyne precursor to this
material was readily prepared as a single diastereoisomer through
alkylation of lactol 9 with propargyl bromide using potassium
bis(trimethyl)silylamide in tetrahydrofuran at room temperature.
Stannylation of 10 following the usual procedures afforded crude 11
upon work up, which was subsequently treated with boron trifluoride
etherate in dichloromethane at -10°C. Work up and purification afforded
2
conditions and in high yield. Prior to this work, a few examples of this
type of rearrangement had been reported for vinylic, phenolic4 and
3
5
allylic ether systems. However, the potential of a general anomeric
oxygen to carbon rearrangement using a wider range of more
synthetically useful nucleophiles has remained largely unexplored.
In this communication we wish to report the reaction of alkynyl
stannanes as the nucleophilic carbon component in the rearrangement
sequence. Alkynyl stannanes have been used previously in an
the desired alkynol product 12 in high yield and as a single
diastereoisomer (Scheme 4).7
6
intermolecular fashion to displace anomeric halides. Their ease of
preparation and handling, combined with their inherent reactivity
towards oxonium ion intermediates, made this group ideally suited to
the rearrangement protocol (Scheme 1).
Scheme 1
In our initial investigations commercially available tetrahydropyranyl
propargylic ether was stannylated using butyllithium and tributyltin
chloride following standard procedures to give 1. The rearrangement of
the alkynyl tributylstannane 1 was then investigated using a range of
solvents, concentrations, temperatures and Lewis acids. The optimal
conditions for the reaction required a concentrated solution of the
alkynyl stannane 1 in dichloromethane at -10°C using boron trifluoride
etherate as the mediator for the transformation. Simple aqueous work up
and purification by column chromatography afforded the carbon linked
product 2 in acceptable chemical yield (Scheme 2).
Scheme 4
In a similar fashion the tetrahydrofuranyl propargylic ether 14 was
readily prepared by alkylation of lactol 13 with propargyl bromide.
Tributylstannylation of this material and subsequent treatment of 15
with boron trifluoride etherate under the usual conditions lead to the
desired carbon linked product 16 as
diastereoisomeric products at the newly formed stereogenic centre
Scheme 5).
a
50:50 mixture of
(
We believe that the anomeric oxygen to carbon rearrangement described
above for alkynyl tributylstannanes will be of great utility in the
synthesis of naturally occurring and biologically important compounds.
In addition, due to the ready preparation of both 12 and 16 from the
requisite lactols through alkylation with propargyl bromide and
subsequent rearrangement, we feel that the sequences represented in
schemes 4 and 5 constitute a useful tool in anomeric carbon-carbon
bond formations with potential application in natural product synthesis.
Scheme 2
Application of these best conditions to a series of readily prepared
homologated alkynyl stannanes 3-5, lead in each case, to the carbon-
linked products 6-8 in moderate to good yields (Scheme 3).
Buffet, Marianne F.
