Angewandte
Communications
Chemie
moiety after sp3-hybridation of the boron (syn pentane type
interaction). This interaction is not present in boronate
complex VI. The relief of steric strain[22] in V could explain
a faster 1,2-shift than in VI, leading to the selective amination
of Bax.
Once we controlled the monofunctionalization of dibor-
onates 2, selective difunctionalizations could be designed
[Scheme 3, Eq. (c)]. Starting from spirocyclo 2b, sequential
cross-coupling/oxidation provided spirocyclobutanol 7 as
single product in good overall yield. Moreover, amination
followed by oxidation of 2b afforded spirocyclic amino-
alcohol 6. These transformations represent formal diastereo-
selective hydroxy-arylation and amino-hydroxylation reac-
tions of the cyclobutene. Finally, compounds 8 and 9 were
prepared in high yields by double oxidation and Zweifel
olefination, respectively.[23]
Schemes 2 and 3 show that the diboration of spirocyclo-
butenes 1 is a powerful tool for the assembly of spirocycles
libraries with controlled vectorization. Since the reactions
shown in Scheme 2 and 3 are stereospecific, the development
of an enantioselective diboration of spirocyclobutenes would
provide access to a broad variety of enantioenriched novel
spirocyclic building blocks. To accomplish this goal, we turned
our attention to the use of platinum complexes.[8] The Pt-
catalyzed enantioselective 1,2-diboration of alkenes has been
only reported for terminal olefins.[8] It has been shown that
disubstituted alkenes prevent the diboration. Interestingly,
this lack of reactivity has been observed even in strained
alkenes such as norbornene.[8c] Therefore, at the outset of the
project, we were skeptical about the development of a plat-
inum catalyzed enantioselective diboration of cyclobutenes 1.
We chose spirocyclobutene 1a as a model substrate and
taddol-derived phosphoramidites and phosphonites as ligands
(Scheme 4), due to their success in the diboration of terminal
alkenes. Phosphoramidite (R,R)-L1 provided the desired
compound with moderate yield and low enantiomeric ratio.
Switching to phosphonite (R,R)-L2 improved the yield and
the enantioselectivity. After a fine tuning of the R group on
the aromatic rings of the ligand (L2–L7), and the groups on the
diol back-bond ((R,R)-L8) we found the best results using
(R,R)-L3 (R = Et). Heating a solution of 1a, Pt(dba)3
(3 mol%), (R,R)-L3 (6 mol%), B2pin2 (1 equiv) in toluene
at 558C smoothly afforded (S,S)-2a in excellent yield and
good levels of enantiocontrol. We were pleased to find that
a single recrystallization increased the enantiomeric ratio up
to 98:2.
Scheme 4. Preliminary validation of the enantioselective diboration.
[a] Reaction conditions: 1 (0.1 mmol), B2pin2 (0.1 mmol), Pt(dba)3
(3 mol%), (R,R)-Ligand (6 mol%), toluene (0.2 M), 558C, 16 h. Yield
of isolated (S,S)-2a. e.r. determined by chiral-phase HPLC. [b] e.r. after
a single recrystallization.
Compounds (S,S)-2e, (S,S)-2g and (S,S)-2j were prepared
as representative examples of spirocycles with different
connectors and different ring sizes, with enantiomeric ratios
comparable to that observed for (S,S)-2a (Scheme 5). The
enantiomeric ratio of compound (S,S)-2e was increased to
93:7 through a single recrystallization. Selective Suzuki–
Miyaura cross-coupling reaction of (S,S)-2e provided enan-
tiomerically enriched (S,R)-3d with perfect chirality trans-
fer.[24]
In summary, we have disclosed the ability of spirocyclo-
butenes to provide a platform for the preparation of chiral
spirocycles, through the diastereo- and enantioselective
diboration of the double bond. Selective manipulation of
Scheme 5. Enantioselective diboration. [a] Reaction conditions:
1 (0.1 mmol), B2pin2 (0.1 mmol), Pt(dba)3 (3 mol%), (R,R)-L3
(6 mol%), toluene (0.2 M), 558C, 16 h. Yield of isolated 2. e.r.
determined by chiral-phase HPLC. [b] e.r. after a single recrystalliza-
tion.
the boryl moieties in the products allows unique control on
the directionality and nature of the substituents on the
spirocycle framework. This approach provides facile access to
a wide variety of novel building blocks from a common
intermediate. Further catalytic transformations of the spiro-
cyclobutenes are ongoing and will be reported in due course.
ꢀ 2021 Wiley-VCH GmbH
Angew. Chem. Int. Ed. 2021, 60, 11763 –11768