Bi(cyclopentyl)diol-Derived Boronates in Highly Enantioselective Chiral Phosphoric Acid-Catalyzed Allylation, Propargylation, and Crotylation of Aldehydes

Article abstract of DOI:10.1021/acs.joc.0c01646

In this study, we disclose the catalytic addition of bi(cyclopentyl)diol-derived boronates to aldehydes promoted by chiral phosphoric acids, allowing for the formation of enantioenriched homoallylic, propargylic, and crotylic alcohols (up to >99% enantiom

Full text of DOI:10.1021/acs.joc.0c01646

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Article
Bi(cyclopentyl)diol-Derived Boronates in Highly Enantioselective
Chiral Phosphoric Acid-Catalyzed Allylation, Propargylation, and
Crotylation of Aldehydes
Jinping Yuan, Pankaj Jain, and Jon C. Antilla*
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ABSTRACT: In this study, we disclose the catalytic addition of bi(cyclopentyl)diol-derived boronates to aldehydes promoted by
chiral phosphoric acids, allowing for the formation of enantioenriched homoallylic, propargylic, and crotylic alcohols (up to >99%
enantiomeric excess (ee), diastereomeric ratio (dr) >20:1). These boronate substrates provided superior enantioselectivities,
allowing for the reactions to proceed with low catalyst loading (0.5−5 mol %) and reduced reaction time (15 min at room
temperature for aldehyde allylboration). A wide substrate scope was exhibited, and the novel boronates provided high
enantiocontrol. Reactions with substituted allylboronates and aldehydes yielded vicinal stereogenic alcohols bearing β-tertiary or
quaternary carbon centers. High enantio- and diastereoselectivities were found due to the closed six-membered chair-like transition
state, with backbone modifications of the boronate and its interactions with the chiral phosphoric acid being the most likely
contributing factor.
ruthenium-catalyzed asymmetric allyl-/crotyl-/propargylations
via alcohol-mediated hydrogen autotransfer, which exploits
nonmetallic allyl acetate, butadiene, and enyne pronucleo-
philes.7 Despite enantioselectivities being high in some cases,
the highly efficient route to produce enantiopure and vicinal
stereogenic homoallyl/propargylic alcohols with a broad
substrate scope under organocatalytic conditions is still
attractive to many.
In 2010, triisopropylphenyl-substituted BINOL phosphoric
acid, TRIP-PA8 (PA1), was applied as a robust chiral catalyst
in the allylboration of aldehydes by our group.9 This method
has resulted in significant use in synthesis10 and has spurred
the development of new methods by others.11,12 Most of these
aldehyde allylation and allenylation reactions utilize TRIP-PA
1. INTRODUCTION
Asymmetric carbonyl allylation, propargylation, and crotylation
represent important and powerful processes in stereoselective
synthesis.1 Optically active β-substituted alkanols with terminal
alkynes/alkenes are found with high frequency in enantiospe-
cific polyketide-derived natural product construction2 (Scheme
1a), with methods development in this area therefore of great
interest. Generally, methods for preparing chiral homoallyl/
propargyl or crotylic alcohol systems rely on the addition of
the nucleophilic allyl/allenyl reagent to achiral aldehydes for
new carbon−carbon bond formation (Scheme 1b).3,4
Hoffmann published the first enantioselective aldehyde
allylation employing a camphor-derived allylboronic ester
(1978).4a Subsequently, the labs of Brown,4b Roush,4c
Cory,4d Leighton,4e Yamamoto,4f Aggarwal,4g Singaram,4h
Denmark,5a−c and others5d,4i reported allyl-, propargyl-, and
crotylations mediated by Lewis acids, modified chiral ligand/
metal catalysts, or even chiral auxiliaries in the last 2 decades.
Additionally, Hoveyda reported an efficient pathway for the
asymmetric synthesis of homoallylic alcohols using chiral
aminophenol-based reagents or the N-heterocyclic carbene
(NHC)−Cu complex as catalysts.6 Krische reported iridium or
Received: July 10, 2020
Published: September 22, 2020
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© XXXX American Chemical Society
J. Org. Chem. XXXX, XXX, XXX−XXX
A

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Scheme 1. Background of Enantioselective Allylation of Aldehydes
Scheme 2. Chiral Phosphoric Acid (CPA)-Catalyzed Allyl-/Propargylations with Boronates and Aldehydes
as the catalyst, along with boronates derived from pinacol to
attain high enantiocontrol (Scheme 2a). However, a relatively
high catalyst loading (20 mol %)11a or long reaction time (96 h
for propargylation)11a was required in some cases.
catalyzed allyl/propargylation of pinacol boronates and
benzaldehyde have been reported by Goodman and Houk
independently.13 Density functional theory (DFT) calculations
suggested that the homoallyl/propargylic product’s major
isomer was generated by the bifunctional activation, which
involves hydrogen bonding between boronate oxygen and the
hydroxyl group of the catalyst with additional stabilization of
the phosphoryl oxygen atom to the formyl hydrogen on the
aldehyde. The enantioselectivity is believed to arise from steric
interactions between bulky triisopropylphenyl groups on (R)-
TRIP-PA and methyl groups on pinacol boronate for CPA-
catalyzed allylation. Consequently, the enantioselectivity would
be affected by the hindrance of the catalyst or boronate.
Herein, we report a novel method of using CPA-catalyzed
In catalytic synthesis, it has always been challenging to
reduce catalyst quantity while retaining high enantio- and
diastereoselectivity. In our initial insight into the allylation
reaction mechanism, we proposed the aldehyde allylation with
pinacol-derived boronate via (R)-TRIP-PA catalysis involving a
closed six-membered chair-like transition state (TS), while the
Lewis acid-catalyzed asymmetric allylation with allylsilanes and
stannanes of aldehydes proceeded with an open-chain
transition model (Scheme 1b).5 In subsequent years after
our initial paper, computational studies on (R)-TRIP-PA-
B
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a
Table 1. Enantioselectivity with Modified Boronates
a
Reaction conditions: all reactions were performed with 1 (0.10 mmol), B1 or B2 (0.12 mmol), 5 mol % catalyst, 50 mg 4 Å molecular sieve (MS),
b
c
d
and 1 mL solvent. Complete conversion was found in all cases. PA1 (2 mol %) was used, and the reaction was completed in 15 min. PA1 (2 mol
%) was used.
bi(cyclopentyl)diol-derived boronates for allylation, propargy-
lation, and crotylation of aldehydes based on mechanistic
speculation. The use of backbone-modified boronates in the
reaction not only reduces chiral catalyst loading under room
temperature conditions but also high stereocontrol is retained.
We also report additional examples of chiral homoallylic
alcohols with β-tertiary or quaternary carbon centers in this
study (Scheme 2b).
Information for more details on catalyst rescreening). We then
chose 5 mol % 2,4,6-cyclohexylphenyl-substituted BINOL
phosphoric acid PA2 as a bulkier catalyst than PA1, and the
reaction achieved 93% ee at room temperature in toluene
(entry 2). This enantioselectivity was equal to that attained by
PA1 with toluene as the solvent. Additionally, the
enantioselectivity was 94% in cyclohexane at room temperature
with 5 mol % PA2 (entry 3).
Since the use of bulkier catalyst PA2 did not have a
significant influence on the enantioselectivity, we concentrated
on modifying the backbone on the allylboronate. The reaction
of bi(cyclopentyl)diol-derived allylic boronate B2 and
benzaldehyde successfully afforded 2 with 99% enantioselec-
tivity at room temperature in cyclohexane in the presence of 5
mol % PA1 catalysis (entry 4). Boronate B2 was synthesized
by reacting bi(cyclopentyl)diol with allylboronic acid. When
boronate B2 was used along with 5 mol % catalyst PA2 at
room temperature, 94% ee was obtained (entry 5). The
reaction catalyzed by 5 mol % PA3 gave only 77% ee in
cyclohexane (entry 6). We further reduced PA1 loading to 2
mol %, the reaction with B2 at room temperature gave >99%
ee with 100% conversion in less than 15 min (entry 7, method
2. RESULTS AND DISCUSSION
The initial studies followed allylboration with benzaldehyde
(Table 1). In our earlier report, allylation between pinacol-
derived allylboronate B1 and benzaldehyde catalyzed by 5 mol
% PA1 in toluene could achieve 93% enantiomeric excess (ee)
at room temperature (entry 1).8 In this investigation, we have
rescreened different catalysts for allylboration, as some results
published previously could be impacted by some metal
impurities from silica gel. The results were different as all of
the catalysts screened in the previous paper were not washed
with HCl after purification by column chromatography on
silica gel.8 With 5 mol % acidified PA1, we found that the ee
was 94%, which was similar to the 93% ee (see the Supporting
C
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Scheme 3. Substrate Scope of Asymmetric-Substituted Allylboration of Aldehydes
a
b
Isolated yields. The configurations were determined by chiral high-performance liquid chromatography (HPLC) analysis and optical rotation
c
d
e
data in the literature. 0.5 mol % PA1 employed at −30 °C. PA3 was used in part B for aliphatic aldehyde examples. Determined by 1H NMR
analysis of crude products.
A). To test the efficiency of this aldehyde allylation method
with B2, we attempted the reduced catalyst loading at lower
temperatures. We found that >99% ee was obtained with only
2 mol % PA1 at −30 °C in toluene (entry 8, method B).
Usually, catalytic or noncatalytic asymmetric allylborations of
aldehydes are carried out at −78 °C. To our knowledge, this
study is the first report furnishing high selectivity’s up to >99%
ee at room temperature with only 2 mol % catalyst loading for
enantioselective allylation of aldehydes.
mol % PA1 at room temperature in cyclohexane, the reaction
of a large range of aldehydes with electron-withdrawing and
electron-donating groups at different positions on the aromatic
ring with B2 provided excellent yields and enantioselectivities
(examples 2−9). Excellent enantioselectivities of 97 and 99%
were also presented with heteroaromatic, and α, β-unsaturated
aldehydes (examples 10 and 11, respectively). In addition, we
synthesized homoallylic propargylic alcohol in 92% yield and
with 99% ee (example 12). Surprisingly, we found that in the
presence of only 0.5 mol % PA1, the reaction of B2 and
We then explored the substrate scope of the aldehyde
allylboration (Scheme 3A). With method A, which utilized 2
D
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a
Table 2. Asymmetric Propargylation
a
Reaction conditions: all propargylations were performed with 1 (0.10 mmol), B9 or B10 (0.12 mmol), 5 mol % catalyst, 50 mg 4 Å MS, and 1 mL
b
c
solvent. Complete conversion seen in all cases. 20 mol % PA1.
benzaldehyde at −30 °C in toluene proceeded with >99% ee
(example 2, method B).
anti-products during C−C bond formation. When reacted with
trans-crotyl boronate B3, a wide range of aldehydes with
electron-rich and electron-poor groups on the aromatic ring
was investigated for diastereo- and enantioselectivity with only
2 mol % PA1 as the catalyst at −30 °C (Scheme 3C, method
B). The products were major anti-homocrotylic alcohols with
>90% yields, 95−99% enantioselectivities, and up to
diastereomeric ratio (dr) >20:1 (examples 17−22). Addition-
ally, we used heteroaryl, polycyclic aromatic, α,β-unsaturated,
and aliphatic aldehydes to react with B3, providing excellent
yields (90−94%) and enantio-/diastereoselectivities (91−99%
ee, up to dr > 20:1, examples 23−29) for the anti-products.
Furthermore, γ-substituted boronates B4−B7 of both trans-
and cis-isomers were well transformed into good yields (87−
97%) and with high enantio- and diastereoselectivities (ee >
90%, see examples 31−34) into the corresponding anti/syn-
alcohols with β-quaternary chiral carbon centers (Scheme 3D).
Cyclohexene-derived boronate B8 could be tolerated to give
alcohol products with 94% yield and 23% ee (example 35).
These enantioenriched homoallylic alcohols with extended
carbon chains on the β-position could be used as asymmetric
intermediates in synthesis, with this as a potential practical
application. Notably, the absolute configuration of 29 was
determined by its ester derivative 30, and X-ray analysis
Subsequently, the scope of aliphatic aldehydes was
investigated (Scheme 3B). As reported in our previous
allylations, only moderate enantioselectivities with aliphatic
aldehydes could be found even with larger catalyst quantities
(S)-TRIP-PA (73−87% ee).8 In this study, we found that
when catalyzed by (R)-H8-TRIP-PA (PA3), the enantiose-
lectivity of the reaction of hydrocinnamyl aldehyde and
bi(cyclopentyl)diol-derived allylboronate B2 was improved to
95% ee with method B (example 13) (see the Supporting
Information for rescreening details on aliphatic aldehydes).
Additional aliphatic-substituted aldehydes were also evaluated.
Allylation with phenylacetaldehyde was shown to provide 93%
yield with 95% ee (example 14). The reaction of benzylox-
yacetaldehyde and B2 gave 96% yield and 93% enantiose-
lectivity, while pinacol boronate B1 showed only 79% ee in our
earlier report under similar conditions (example 15).8 The
reaction with cyclohexanecarboxaldehyde and B2 gave 92%
yield with 87% ee in the presence of 2 mol % PA3 (example
16).
The crotylboration with aldehydes is a powerful strategy for
β-methyl alkanol construction with two newly formed
stereocenters. The crotylation process translates the geometry
of the double bond on the crotylic reagent into relative syn/
E
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Scheme 4. Substrate Scope of Asymmetric Propargylation of Aldehydes with B10
a
b
Isolated yields. The configurations were determined by chiral HPLC analysis and optical rotation data in the literature.
provided the absolute stereochemistry of this anti-ester with
two adjacent chiral centers.14
To demonstrate the potential application of these
asymmetric transformations, we applied the chiral homocro-
tylic alcohol to the synthesis of pharmaceutical intermediates
(Scheme 5). Homocrotylic alcohol 19 was reacted with N-Boc-
protected L-valine 46 to produce 47 with an identical 99% ee
via Mitsunobu reaction. The furnished chiral amino acid 47
was a crucial chiral intermediate for the synthesis of
nannocystin analogue 48, which is a potent factor 1 inhibitor
(Scheme 5a).15 Moreover, diene-derived intermediate 49 was
accessed by treatment with acryloyl chloride with little ee
degradation from the starting alcohol. With Grubbs second-
generation ruthenium catalyst under ring-closing metathesis
conditions, pyranone 50 (83% ee, dr > 20:1) was obtained
with a slight loss in ee (Scheme 5b). This procedure could be
used for the synthesis of cyclic olefins of various ring sizes with
the enantioenriched alcohols developed in our study as the
starting material. Gram-scale reactions were carried out for
practical utility tests. Excellent yields and enantio-/diaster-
eoselectivities were realized for allylation (97 and 99% ee),
crotylation (97 and 93% ee, dr > 20:1), and propargylation (97
and 98% ee) when conducted at the 10 mmol scale with
benzaldehyde (Scheme 5c). The catalyst could be isolated in
an 84% recovery rate from silica gel column chromatography
with 5% methanol in dichloromethane (DCM) and then
reacidified with 6 M HCl.
We investigated the propargylboration of aldehydes, which
has a slower reaction rate than that of aldehyde allylboration
(Table 2). Previously, we reported that propargylation with
allenyl pinacol boronate B9 and benzaldehyde gave 91% ee in
toluene at −20 °C with 20 mol % PA1 catalysis (entry 1).11a In
this optimization, our examination started by employing 5 mol
% PA1 in toluene with B9 at room temperature, and 77% ee
was achieved (entry 2). When cyclohexane was used as the
solvent and the reaction catalyzed by 5 mol % PA1 at room
temperature with B9, the enantioselectivity was 88% (entry 3).
This improvement in enantioselectivity indicated that cyclo-
hexane was a superior solvent at room temperature. The
reaction with B9 and benzaldehyde catalyzed by 5 mol % PA1
in cyclohexane gave 92% ee at 10 °C (entry 4).11b With the use
of cyclohexane, propargylation of B9 and benzaldehyde
catalyzed by the relatively bulky substituted 5 mol % PA2
gave 87% ee (entry 5). When bi(cyclopentyl)diol-derived
allenyl ester B10 and benzaldehyde reacted at room temper-
ature along with cyclohexane under 5 mol % PA1 catalysis,
98% ee was obtained (entry 6). The reaction of allenylbor-
onate B10 with the bulkier catalyst PA2 gave 95% ee in
cyclohexane (entry 7). The reaction of B10 with PA3 gave
74% enantioselectivity at room temperature (entry 8).
The substrate scope for the propargylation of B10 and
aldehydes was then examined with 5 mol % PA1 at room
temperature in cyclohexane (Scheme 4). Compared to earlier
propargylation with B9 and benzaldehyde,10a,b we found that
with B10, the reaction times were shorter and superior
enantioselectivities were achieved at room temperature. A
broad range of homopropargylic alcohols was produced in high
yields (91−96%) and with high enantioselectivities (91−99%
ee) from different substituted aryl, heteroaromatic, and α,β-
unsaturated aldehydes (examples 36−45).
A general catalytic mechanism with the importance of steric
interactions of the bicyclopentyl boronate and Brønsted acid
catalyst was assumed (Scheme 6a). We believe that the
reaction occurred through a bifunctional activation mode and
underwent a chair-like six-membered ring cyclic TS that
involved interaction of the pseudoaxial oxygen of boronate
with the (R)-TRIP-PA hydroxyl hydrogen and stabilization of
the formyl hydrogen on an aldehyde with the phosphoryl
oxygen on the catalyst. This distortion of the “catalyst−
boronate complex” indicated that a bulkier boronate ester
F
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Scheme 5. Synthetic Application Studies
group was consistent with increased stereoscopic repulsion. In
this re-face favored attack model, bicyclopentyl boronate ester
groups were directed toward the empty pocket of (R)-TRIP-
PA, accounting for gauche interactions with the isopropyl-
phenyls on the catalyst. The homoallylic intermediate 54
would easily hydrolyze to the corresponding alcohol (Scheme
6a). We conducted some benzaldehyde allylborations with 1,3-
propanediol and ethylene glycol-derived allylboronates, in
which the boronate ester group was relatively small (B11 and
B12). Lower enantioselectivities were observed and are shown
in Scheme 6b (entries 1−4). Less than 50% ee was achieved at
−78 °C, and even racemic products were formed at room
temperature. The isopropanol-derived allylboronate (B13) was
tested with benzaldehyde; enantioselectivity was 20% at room
temperature and 32% at −78 °C (entries 5 and 6).
3. CONCLUSIONS
In this study, we identified bi(cyclopentyl)diol-derived allyl/
allenyl boronates as superior nucleophiles for (R)-TRIP-PA-
catalyzed allylation, propargylation, and crotylation of
aldehydes. The reactions could proceed at room temperature
or −30 °C with 0.5−5 mol % catalyst loading. Wide ranges of
G
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Scheme 6. Catalyst Backbone: Impact on Selectivity
a
Reaction conditions: all reactions were performed with 1 (0.10 mmol), B11−B13 (0.12 mmol), 5 mol % catalyst, 50 mg 4 Å MS, and 1 mL
b
c
d
1
solvent. Determined by H NMR analysis. The ee was determined by chiral HPLC analysis. The configurations were determined by chiral
HPLC and optical rotation data in the literature.
substrates were evaluated, and the reactions gave excellent
yields and enantio- and diastereoselectivities (up to >99% ee,
dr > 20:1). A bifunctional activation mode was assumed, and
X-ray crystallography of a fully characterized anti-homoallylic
alcohol confirmed the stereochemistry. These methods could
be used in the preparations of relevant enantiopure
pharmaceutical and natural product intermediates. Further
expansion of substituted allylboration and propargylboration of
aliphatic aldehydes are currently under investigation and will
be reported in due course.
4. EXPERIMENTAL SECTION
4.1. General. All reactions were carried out in flame-dried screw-
cap test tubes and were allowed to proceed under a dry argon
atmosphere with magnetic stirring. Toluene was purified by passing
through a column of activated alumina under a dry argon atmosphere.
H
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Anhydrous cyclohexane was purchased from Acros and directly used.
Aldehydes were purchased from Adamas-β and were distilled prior to
use if required. Thin-layer chromatography (TLC) was performed on
Yantai TLC plates (silica gel 60 F254). Visualization was accomplished
by UV light (256 nm), with the combination of ceric ammonium
molybdate or potassium permanganate as the indicator. Flash column
chromatography was performed using Yantai silica gel (200−300
mesh). Enantiomeric excess (ee) was determined using a Varian
Prostar HPLC system with a 210 binary pump and a 335 diode array
detector; Agilent HPLC 1260 and Shimadzu HPLC LC-20AT.
Optical rotations were performed on a Rudolph Research Analytical
Autopol IV polarimeter (λ 589) using a 700 μL cell with a path length
of 1 dm. 1H NMR and 13C NMR were recorded on a Bruker
AVANCE IIITM HD NanoBAY (400 MHz) and Bruker AVANCE
III (600 MHz) spectrometer with chemical shifts reported relative to
tetramethylsilane (TMS). The high-resolution mass spectrometry
(HRMS) data were measured on Thermo Fisher Q Exactive HF
Orbitrap.
4.2. Preparation for the Bi(cyclopentyl)diol-Derived Boro-
nate Substrates. 4.2.1. Synthesis of Diboron [1,1′-Bi-
(cyclopentane)]-1,1′-diol Ester. In a flame-dried, two neck round-
bottom flask, equipped with a magnetic stir bar, were placed 1.0 equiv
tetrahydroxydiboron and 2.0 equiv [1,1′-bicyclopentyl]-1,1′-diol. Dry
toluene was added, and the solution was stirred under argon at 110
°C for 24 h. Then, the reaction mixture was cooled to room
temperature, the solvent was evaporated, and then concentrated in
vacuo to produce a white solid in 91% yield. mp = 107−108 °C.
Diboron [1,1′-bi(cyclopentane)]-1,1′-diol ester: 1H NMR (600 MHz,
CDCl3) δ 1.87−1.51 (m, 32H). 13C{1H} NMR (151 MHz, CDCl3) δ
92.0, 34.8, 22.1. HRMS (electrospray ionization (ESI)) calcd for
C20H32B2O4 ([M + H]+) m/z 359.2559, found 359.2555.
23.8, 20.3, 17.8. HRMS (ESI) calcd for C8H12O2 ([M + Na]+) m/z
163.0729, found 163.0728.
4.2.3.4. (E)-Hex-2-en-1-yl Acetate (AC4). The product was
obtained by distillation (59−60 °C, 3 mmHg) to give a colorless
1
oil. 92% yield. H NMR (600 MHz, CDCl3) δ 5.75−5.64 (m, 1H),
5.56−5.42 (m, 1H), 4.43 (d, J = 6.6 Hz, 2H), 2.00−1.91 (m, 5H),
1.39−1.27 (m, 2H), 0.83 (td, J = 7.4, 1.4 Hz, 3H). 13C{1H} NMR
(151 MHz, CDCl3) δ 169.8, 135.3, 122.9, 64.2, 33.3, 21.0, 19.9, 12.6.
HRMS (ESI) calcd for C8H14O2 ([M + H]+) m/z 143.1066, found
143.1066.
4.2.3.5. (E)-12-(But-2-en-1-yl)-11,13-dioxa-12-oradispiro-
[4.0.46.35]tridecane (B3). The product was obtained by flash column
chromatography (pentane/ether, 50:1) as a colorless oil. 81% yield.
1H NMR (600 MHz, CDCl3) δ 5.47−5.25 (m, 2H), 1.79−1.77 (m,
2H), 1.70−1.48 (m, 19H). 13C{1H} NMR (151 MHz, CDCl3) δ
126.2, 125.0, 93.1, 35.7, 23.0, 18.0. HRMS (ESI) calcd for C14H23BO2
([M + H]+) m/z 235.1860, found 235.1860.
4.2.3.6. 12-(3-Methylbut-2-en-1-yl)-11,13-dioxa-12-boradispiro-
[4.0.46.35]tridecane (B4). The product was obtained by flash column
chromatography (pentane/ether, 50:1) as a colorless oil. 86% yield.
1H NMR (600 MHz, CDCl3) δ 5.15 (ddd, J = 7.6, 4.6, 1.4 Hz, 1H),
1.78 (dd, J = 4.5, 2.4 Hz, 2H), 1.70−1.47 (m, 22H). 13C{1H} NMR
(151 MHz, CDCl3) δ 130.3, 117.7, 92.0, 34.6, 24.6, 22.0, 16.6. HRMS
(ESI) calcd for C15H25BO2 ([M + Na]+) m/z 271.1839, found
271.1837.
4.2.3.7. (E)-12-(3,7-Dimethylocta-2,6-dien-1-yl)-11,13-dioxa-12-
boradispiro[4.0.46.35]tridecane (B5). The product was obtained by
flash column chromatography (pentane/ether, 50:1) and then
distillation (176−177 °C, 3 mmHg) as a colorless oil. 81% yield.
1H NMR (600 MHz, CDCl3) δ 5.61−4.93 (m, 2H), 2.05−1.88 (m,
4H), 1.84−1.38 (m, 27H). 13C{1H} NMR (151 MHz, CDCl3) δ
134.9, 131.1, 124.5, 118.8, 93.0, 39.7, 35.6, 26.8, 25.7, 23.1, 17.7, 15.9.
HRMS (ESI) calcd for C20H33BO2 ([M + H]+) m/z 317.2646, found
317.2642.
4.2.2. Synthesis of Allylboronate B2 from [1,1′-Bicyclopentyl]-
1,1′-diol. The allylboronate B2 was synthesized from [1,1′-
bicyclopentyl]-1,1′-diol (CAS 5181-75-9) following the literature
procedure16 for the synthesis of B-allyl-1,3,2-dioxaborinane. The
boronate B2 was obtained as a colorless oil in 83% yield. 12-Allyl-
4.2.3.8. (Z)-12-(3,7-Dimethylocta-2,6-dien-1-yl)-11,13-dioxa-12-
boradispiro[4.0.46.35]tridecane (B6). The product was obtained by
flash column chromatography (pentane/ether, 50:1) and then
distillation (174−175 °C, 3 mmHg) as a colorless oil. 78% yield.
1H NMR (400 MHz, CDCl3) δ 5.68−4.90 (m, 2H), 2.15−1.84 (m,
1
11,13-dioxa-12-boradispiro[4.0.46.35]tridecane (B2): H NMR (600
MHz, CDCl3) δ 5.88−5.68 (m, 1H), 4.95−4.72 (m, 2H), 1.78 (d, J =
5.0 Hz, 2H), 1.73−1.41 (m, 16H). 13C{1H} NMR (151 MHz,
CDCl3) δ 133.3, 113.5, 92.1, 34.6, 21.9. HRMS (ESI) calcd for
C13H21BO2 ([M + Na]+) m/z 243.1527, found 243.1520.
4.2.3. Synthesis of Substituted Allylic Reagents B3−B8. The
noncommercially available allylic acetate substrates were generally
prepared by the acetylation of the corresponding allylic alcohols or
allylic chlorides. Following Morken’s literature,17 procedures were a
little modified for the synthesis of B3−B8.
4.2.3.1. (Z)-3,7-Dimethylocta-2,6-dien-1-yl Acetate (AC1). The
product was obtained by distillation (108−110 °C, 3 mmHg) to give
a colorless oil. 85% yield. 1H NMR (400 MHz, CDCl3) δ 5.29 (t, J =
7.2 Hz, 1H), 5.02 (t, J = 5.6 Hz, 1H), 4.48 (d, J = 7.3 Hz, 2H), 2.03
(t, J = 5.6 Hz, 4H), 1.97 (d, J = 2.2 Hz, 3H), 1.69 (s, 3H), 1.61 (s,
3H), 1.53 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 170.0, 141.6,
131.1, 122.5, 118.1, 60.0, 31.1, 25.6, 24.6, 22.4, 20.0, 16.6. HRMS
(ESI) calcd for C12H20O2 ([M + Na]+) m/z 219.1356, found
219.1357.
4H), 1.81−1.34 (m, 27H). 13C{1H} NMR (101 MHz, CDCl3) δ
135.0, 131.3, 124.6, 119.3, 92.9, 35.6, 31.8, 26.4, 25.7, 23.5, 23.0, 17.6.
HRMS (ESI) calcd for C20H33BO2 ([M + H]+) m/z 317.2646, found
317.2642.
4.2.3.9. (E)-12-(Hex-2-en-1-yl)-11,13-dioxa-12-boradispiro-
[4.0.46.35]tridecane (B7). The product was obtained by flash column
chromatography (pentane/ether, 50:1) and then distillation (155−
157 °C, 3 mmHg) as a colorless oil. 81% yield. 1H NMR (400 MHz,
CDCl3) δ 5.56−5.11 (m, 2H), 1.89 (dt, J = 14.2, 7.1 Hz, 2H), 1.79−
1.76 (m, 2H), 1.68−1.48 (m, 16H), 1.29 (dt, J = 14.6, 7.4 Hz, 2H),
0.80 (t, J = 7.4 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 130.5,
125.2, 93.1, 35.6, 34.8, 23.0, 22.7, 13.5. HRMS (ESI) calcd for
C16H27BO2 ([M + H]+) m/z 263.2176, found 263.2170.
4.2.3.10. 12-(Cyclohex-2-en-1-yl)-11,13-dioxa-12-boradispiro-
[4.0.46.35]tridecane (B8). The product was obtained by flash column
chromatography (pentane/ether, 50:1) and then distillation (90−91
1
°C, 3 mmHg) as a colorless oil. 72% yield. H NMR (600 MHz,
4.2.3.2. (E)-3,7-Dimethylocta-2,6-dien-1-yl Acetate (AC2). The
product was obtained by distillation (109−111 °C, 3 mmHg) to give
a colorless oil. 83% yield. 1H NMR (600 MHz, CDCl3) δ 5.27 (t, J =
7.6 Hz, 1H), 5.01 (t, J = 6.8 Hz, 1H), 4.52 (d, J = 7.1 Hz, 2H), 2.07−
1.98 (m, 4H), 1.98 (s, 3H), 1.63 (s, 3H), 1.61 (s, 3H), 1.53 (s, 3H).
13C{1H} NMR (151 MHz, CDCl3) δ 170.1, 141.2, 130.8, 122.7,
117.2, 60.3, 38.5, 25.2, 24.6, 20.0, 16.6, 15.4. HRMS (ESI) calcd for
C12H20O2 ([M + H]+) m/z 197.1534, found 197.1535.
4.2.3.3. Cyclohex-2-en-1-yl Acetate (AC3). The product was
obtained by distillation (49−50 °C, 3 mmHg) to give a colorless oil.
89% yield. 1H NMR (600 MHz, CDCl3) δ 5.88 (d, J = 17.3 Hz, 1H),
5.63 (d, J = 11.9 Hz, 1H), 5.18 (s, 1H), 2.04−1.88 (m, 5H), 1.80 (t, J
= 15.3 Hz, 1H), 1.66 (d, J = 11.5 Hz, 2H), 1.59−1.53 (m, 1H).
13C{1H} NMR (151 MHz, CDCl3) δ 169.6, 131.5, 124.7, 67.0, 27.3,
CDCl3) δ 5.71−5.44 (m, 2H), 2.05−1.85 (m, 2H), 1.83−1.69 (m,
5H), 1.66−1.45 (m, 16H). 13C{1H} NMR (151 MHz, CDCl3) δ
127.9, 125.8, 93.0, 35.7, 35.5, 25.0, 24.1, 23.1, 22.5. HRMS (ESI)
calcd for C16H25BO2 ([M + H]+) m/z 261.2020, found 261.2019.
4.2.4. Synthesis of Allenylboronate B10. The boronate B10 was
synthesized from allenylboronic acid pinacol ester following the
literature procedure18 for the synthesis of propanediolboronates (see
the Supporting Information, a representative procedure for propane-
diolboronates (13, 16, 17): Pei, W.; Krauss, I. J. J. Am. Chem. Soc.
2011, 133, 18514). The boronate B10 was obtained in 82% yield as a
colorless oil. 12-(Propa-1,2-dien-1-yl)-11,13-dioxa-12-boradispiro-
1
[4.0.46.35]tridecane (B10). H NMR (400 MHz, CDCl3) δ 4.91 (t,
J = 7.0 Hz, 1H), 4.61 (d, J = 7.0 Hz, 2H), 1.94−1.54 (m, 16H).
13C{1H} NMR (101 MHz, CDCl3) δ 217.8, 92.6, 68.8, 34.6, 22.0.
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HRMS (ESI) calcd for C13H19BO2 ([M + Na]+) m/z 241.1370, found
241.1362.
4.4.5. (R)-1-(3-Methoxy-phenyl)-but-3-en-1-ol (6). Colorless oil in
98% yield. Enantiomeric excess was determined by HPLC with a
Chiralpak AD-H column (hexane/iPrOH = 98/2, 1.0 mL/min), tminor
= 23.81 min, tmajor = 25.75 min; ee = 99%. [α]D24 = +55.09 (c = 1.12,
benzene). The absolute configuration was determined by analogy. 1H
NMR (600 MHz, CDCl3) δ 7.19 (dd, J = 9.7, 6.4 Hz, 1H), 6.86 (dd, J
= 4.5, 2.3 Hz, 2H), 6.75 (ddd, J = 8.3, 2.5, 0.8 Hz, 1H), 5.80−5.66
(m, 1H), 5.15−5.03 (m, 2H), 4.65 (dd, J = 7.9, 4.9 Hz, 1H), 3.75 (s,
3H), 2.44 (qt, J = 14.2, 7.1 Hz, 2H), 1.99 (s, 1H). 13C{1H} NMR
(151 MHz, CDCl3) δ 158.7, 144.6, 133.4, 128.4, 117.4, 117.1, 112.0,
110.3, 72.2, 54.2, 42.7. HRMS (ESI) calcd for C11H14O2 ([M + H]+)
m/z 179.1066, found 179.1065.
4.3. General Procedure for the Allylation of Aldehydes,
Method A. A screw-cap reaction tube with a stir bar and 4 Å MS (50
mg) was evacuated, flame-dried, and back-filled with argon. To this
tube were added the (R)-TRIP-PA catalyst PA1 (2 mol %), freshly
distilled aldehyde (0.1 mmol), and 1.0 mL of dry cyclohexane. Then,
allylboronate B2 (0.12 mmol) was added to the reaction mixture
dropwise over 30 s. The reaction mixture was stirred for 15 min at
room temperature (TLC shows complete conversion of the aldehyde)
and then directly loaded on a silica gel column, and the crude product
was purified by flash chromatography using ethyl acetate (EA) and
hexane (1:9).
4.4. General Procedure for the Allylation of Aldehydes,
Method B. A screw-cap reaction tube with a stir bar and 4 Å MS (50
mg) was evacuated, flame-dried, and back-filled with argon. To this
tube were added the (R)-TRIP-PA catalyst PA1 (2 mol %), freshly
distilled aldehyde (0.1 mmol), and 1.0 mL of dry toluene. Then, the
reaction mixture was then cooled to −30 °C, followed by the addition
of allylboronate B2 (0.12 mmol), dropwise over 30 s. The reaction
mixture was stirred for 6 h at this temperature (TLC shows complete
conversion of the aldehyde) and then directly loaded on a silica gel
column, and the crude product was purified by flash chromatography
using ethyl acetate and hexane (1:9).
4.4.6. (R)-1-o-Tolyl-but-3-en-1-ol (7). Colorless oil in 94% yield.
Enantiomeric excess was determined by HPLC with a Chiralcel AD-H
column (hexane/iPrOH = 95/5, 1.0 mL/min), tmajor = 6.56 min,
24
t
minor= 7.43min; ee = 99%. [α]D = +70.77 (c = 1.2, benzene). The
reported value19 for the R-enantiomer (97% ee) is [α]D = +75.5 (c =
1.0, benzene). H NMR (400 MHz, CDCl3) δ 7.40 (d, J = 7.5 Hz,
1
1H), 7.17−7.03 (m, 3H), 5.84−5.69 (m, 1H), 5.15−5.04 (m, 2H),
4.89 (dd, J = 8.2, 4.5 Hz, 1H), 2.41 (dddd, J = 26.1, 22.2, 10.2, 5.5 Hz,
2H), 2.26 (s, 3H), 1.90 (s, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ
140.9, 133.7, 133.3, 129.3, 126.2, 125.2, 124.1, 117.2, 68.6, 41.6, 18.0.
HRMS (ESI) calcd for C11H14O ([M + H]+) m/z 163.1117, found
163.1116.
4.4.7. (R)-Methyl 4-(1-hydroxybut-3enyl)benzoate (8). Colorless
oil in 93% yield. Enantiomeric excess was determined by HPLC with a
Chiralpak AD-H column (hexane/iPrOH = 95/5, 1.0 mL/min), tmajor
4.4.1. (R)-1-Phenyl-but-3-en-1-ol (2). Colorless oil in 95% yield.
Enantiomeric excess was determined by HPLC with a Chiralcel OD-
H column (hexane/iPrOH = 99/1, 0.7 mL/min), tmajor = 28.61 min,
24
24
= 13.17 min, tminor = 14.99 min; ee = 97%. [α]D = 28.08 (c = 1.07,
tminor = 33.53 min; ee = 99%. [α]D = +57.23 (c = 1.07, benzene).
benzene). The absolute configuration was determined by analogy. 1H
NMR (600 MHz, CDCl3) δ 7.94 (d, J = 8.3 Hz, 2H), 7.36 (d, J = 8.2
Hz, 2H), 5.72 (dddd, J = 11.4, 9.4, 7.7, 6.7 Hz, 1H), 5.10 (dd, J =
10.8, 6.4 Hz, 2H), 4.73 (dd, J = 8.0, 4.8 Hz, 1H), 3.84 (s, 3H), 2.51−
2.36 (m, 2H), 2.16 (s, 1H). 13C{1H} NMR (151 MHz, CDCl3) δ
165.9, 147.9, 132.8, 128.7, 128.2, 124.7, 118.0, 71.7, 51.0, 42.8.
HRMS (ESI) calcd for C12H14O3 ([M + H]+) m/z 207.1016, found
207.1016.
The reported value19 for the R-enantiomer (95% ee) is [α]D = +56.5
1
(c = 1.0, benzene). H NMR (400 MHz, CDCl3) δ 7.31−7.18 (m,
5H), 5.82−5.64 (m, 1H), 5.15−5.02 (m, 2H), 4.67 (dd, J = 7.7, 5.3
Hz, 1H), 2.52−2.40 (m, 2H), 1.81 (s, 1H). 13C{1H} NMR (101
MHz, CDCl3) δ 142.8, 133.4, 127.4, 126.5, 124.7, 117.4, 72.2, 42.8.
HRMS (ESI) calcd for C10H12O ([M + Na]+) m/z 171.0780, found
171.0780.
4.4.2. (R)-1-(4-Bromo-phenyl)-but-3-en-1-ol (3). Colorless oil in
96% yield. Enantiomeric excess was determined by HPLC with a
Chiralpak AD-H column (hexane/iPrOH = 98/2, 1.0 mL/min), tminor
= 13.29 min, tmajor= 14.36 min; ee = 99%. [α]D24 = +25.79 (c = 1.02,
benzene). The reported value19 for the R-enantiomer (96% ee) is
4.4.8. (R)-1-(Benzo[d][1,3]dioxol-5-yl)but-3-en-1-ol (9). Colorless
oil in 97% yield. Enantiomeric excess was determined by HPLC with a
Chiralcel OD-H column (hexane/iPrOH = 98/2, 1.0 mL/min), tmajor
24
= 21.55 min, tminor = 26.97 min; ee = 99%. [α]D = +35.79 c = 1.22,
1
CHCl3). The absolute configuration was determined by analogy. H
1
[α]D = +23.2 (c = 1.17, benzene). H NMR (600 MHz, CDCl3) δ
NMR (600 MHz, CDCl3) δ 6.74 (ddd, J = 29.4, 19.3, 4.7 Hz, 3H),
5.88 (s, 2H), 5.72 (ddt, J = 17.1, 10.2, 7.1 Hz, 1H), 5.12−5.03 (m,
2H), 4.58 (dd, J = 7.1, 5.9 Hz, 1H), 2.40 (td, J = 7.3, 2.2 Hz, 2H),
1.83 (s, 1H). 13C{1H} NMR (151 MHz, CDCl3) δ 146.7, 145.9,
136.9, 133.3, 118.2, 117.3, 107.0, 105.3, 99.9, 72.1, 42.8. HRMS (ESI)
calcd for C11H12O3 ([M + Na]+) m/z 215.0679, found 215.0678.
4.4.9. (R)-1-Thiophen-2-yl-but-3-en-1-ol (10). Colorless oil in 91%
yield. Enantiomeric excess was determined by HPLC with a Chiralcel
OJ-H column (hexane/iPrOH = 99/1, 1.0 mL/min), tminor = 26.12
min, tmajor = 30.45 min; ee = 97%. [α]D24 = +15.78 (c = 0.96, EtOH).
The absolute configuration was determined by analogy. 1H NMR
(600 MHz, CDCl3) δ 7.19−7.15 (m, 1H), 6.92−6.86 (m, 2H), 5.75
(ddt, J = 17.2, 10.2, 7.1 Hz, 1H), 5.17−5.04 (m, 2H), 4.94−4.86 (m,
1H), 2.58−2.51 (m, 2H), 2.22 (s, 1H). 13C{1H} NMR (151 MHz,
CDCl3) δ 146.8, 132.8, 125.6, 123.5, 122.6, 117.7, 68.3, 42.7. HRMS
(ESI) calcd for C8H10OS ([M + Na]+) m/z 177.0345, found
177.0344.
7.40 (d, J = 8.4 Hz, 2H), 7.16 (d, J = 8.4 Hz, 2H), 5.76−5.59 (m,
1H), 5.12−5.05 (m, 2H), 4.63 (dd, J = 7.9, 5.0 Hz, 1H), 2.46−2.35
(m, 2H), 2.00 (s, 1H). 13C{1H} NMR (151 MHz, CDCl3) δ 141.8,
132.9, 130.4, 126.5, 120.2, 117.8, 71.5, 42.8. HRMS (ESI) calcd for
C10H11BrO ([M + Na]+) m/z 248.9885, found 248.9885.
4.4.3. (R)-1-(4-Nitro-phenyl)-but-3-en-1-ol (4). Colorless oil in
96% yield. Enantiomeric excess was determined by HPLC with a
Chiralpak AD-H column (hexane/iPrOH = 98/2, 1.0 mL/min), tmajor
= 34.00 min, tminor = 36.32 min; ee = 99%. [α]D24 = +65.73 (c = 0.91,
1
CHCl3). The absolute configuration was determined by analogy. H
NMR (600 MHz, CDCl3) δ 8.13 (d, J = 8.7 Hz, 2H), 7.46 (d, J = 8.7
Hz, 2H), 5.72 (ddd, J = 17.0, 10.3, 7.2 Hz, 1H), 5.12 (dd, J = 13.2, 9.9
Hz, 2H), 4.80 (dd, J = 8.0, 4.6 Hz, 1H), 2.53−2.35 (m, 2H), 2.20 (s,
1H). 13C{1H} NMR (151 MHz, CDCl3) δ 150.0, 146.2, 132.1, 125.5,
122.6, 118.6, 71.1, 42.9. HRMS (ESI) calcd for C10H11NO3 ([M +
H]+) m/z 194.0811, found 194.0814.
4.4.4. (R)-1-(4-Methoxy-phenyl)-but-3-en-1-ol (5). Colorless oil in
97% yield. Enantiomeric excess was determined by HPLC with a
Chiralcel OD-H column (hexane/iPrOH = 98/2, 1.0 mL/min), tmajor
= 18.04 min, tminor= 23.75 min; ee = 99%. [α]D24 = +30.75 (c = 1.09,
benzene). The reported value20 for the R-enantiomer (95% ee) is
[α]D = +30.5 (c = 1.0, benzene). 1H NMR (600 MHz, CDCl3) δ 7.21
(d, J = 8.6 Hz, 2H), 6.86−6.75 (m, 2H), 5.72 (ddt, J = 17.2, 10.2, 7.1
Hz, 1H), 5.17−4.96 (m, 2H), 4.61 (t, J = 6.5 Hz, 1H), 3.73 (s, 3H),
2.42 (t, J = 6.8 Hz, 2H), 1.95 (s, 1H). 13C{1H} NMR (151 MHz,
CDCl3) δ 158.0, 135.0, 133.6, 126.0, 117.1, 112.7, 71.9, 54.2, 42.7.
HRMS (ESI) calcd for C11H14O2 ([M + Na]+) m/z 201.0886, found
201.0886.
4.4.10. (R,E)-1-Phenylhexa-1,5-dien-3-ol (11). Colorless oil in 94%
yield. Enantiomeric excess was determined by HPLC with a Chiralcel
OD-H column (hexane/iPrOH = 95/5, 1.0 mL/min), tmajor = 13.13
min, tminor = 22.64 min; ee = 99%. [α]D24 = −11.83 (c = 1.03, Et2O).
The reported value19 for the R-enantiomer (97% ee) is [α]D = −12.3
1
(c = 1.0, Et2O). H NMR (600 MHz, CDCl3) δ 7.38 (d, J = 7.6 Hz,
2H), 7.31 (t, J = 7.6 Hz, 2H), 7.26−7.22 (m, 1H), 6.60 (d, J = 15.9
Hz, 1H), 6.24 (dd, J = 15.9, 6.3 Hz, 1H), 5.86 (ddt, J = 17.2, 10.2, 7.1
Hz, 1H), 5.22−5.14 (m, 2H), 4.36 (q, J = 5.7 Hz, 1H), 2.47−2.35 (m,
2H), 1.78 (s, 1H). 13C{1H} NMR (151 MHz, CDCl3) δ 135.6, 133.0,
130.5, 129.3, 127.5, 126.6, 125.4, 117.5, 70.6, 41.0. HRMS (ESI)
calcd for C12H14O ([M + H]+) m/z 175.1117, found 175.1118.
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4.4.11. (R)-1-Phenylhex-5-en-1-yn-3-ol (12). Colorless oil in 92%
yield. Enantiomeric excess was determined by HPLC with a Chiralcel
OD-H column (hexane/iPrOH = 95/5, 1.0 mL/min), tmajor = 9.21
min, tminor = 26.06 min; ee = 99%. [α]D24 = 23.46 (c = 0.21, CHCl3).
The absolute configuration was determined by analogy. 1H NMR
(600 MHz, CDCl3) δ 7.39−7.33 (m, 2H), 7.27−7.20 (m, 3H), 5.89
(ddt, J = 17.3, 10.2, 7.1 Hz, 1H), 5.20−5.12 (m, 2H), 4.59 (t, J = 6.0
Hz, 1H), 2.53−2.47 (m, 2H), 2.02 (s, 1H). 13C{1H} NMR (151
MHz, CDCl3) δ 132.0, 130.6, 127.4, 127.2, 121.5, 118.1, 88.3, 84.2,
61.0, 41.2. HRMS (ESI) calcd for C12H12O ([M + H]+) m/z
173.0960, found 173.0961.
4.5.1. (1R,2R)-2-Methyl-1-phenylbut-3-en-1-ol (17). Colorless oil
in 97% yield. Enantiomeric excess was determined by HPLC with a
Chiralcel OD-H column (hexane/iPrOH = 90/10, 1.0 mL/min),
t
minor = 5.297 min, tmajor = 6.192 min; ee = 95%. [α]D25 = +92.57 (c =
1.05, CHCl3). The reported value12b for the R,R-enantiomer (99% ee)
is [α]D26 = +93.18 (c = 1.09, CHCl3). 1H NMR (600 MHz, CDCl3) δ
7.34−7.19 (m, 5H), 5.80−5.68 (m, 1H), 5.13 (t, J = 13.2 Hz, 2H),
4.29 (d, J = 7.9 Hz, 1H), 2.46−2.37 (m, 1H), 2.09 (s, 1H), 0.80 (d, J
= 6.8 Hz, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 141.4, 139.6,
127.2, 126.6, 125.8, 115.8, 76.8, 45.3, 15.5. HRMS (ESI) calcd for
C11H14O ([M + Na]+) m/z 185.0937, found 185.0943.
4.4.12. (R)-1-Phenylhex-5-en-3-ol (13). Colorless oil in 95% yield.
Enantiomeric excess was determined by HPLC with a Chiralcel OD-
H column (hexane/iPrOH = 95/5, 1.0 mL/min), tmajor = 8.77 min,
4.5.2. (1R,2R)-1-(4-Chlorophenyl)-2-methylbut-3-en-1-ol (18).
Colorless oil in 98% yield. Enantiomeric excess was determined by
HPLC with a Chiralcel OD-H column (hexane/iPrOH = 90/10, 1.0
minor = 13.95 min; ee = 95%. [α]D24 = +25.9 (c = 0.89, benzene). The
25
t
mL/min), tminor = 5.166 min, tmajor = 5.455 min; ee = 99%. [α]D
=
1
absolute configuration was determined by analogy. H NMR (600
MHz, CDCl3) δ 7.21 (t, J = 7.6 Hz, 2H), 7.12 (dd, J = 15.7, 7.4 Hz,
3H), 5.84−5.66 (m, 1H), 5.13−5.01 (m, 2H), 3.61 (ddd, J = 12.2,
7.8, 4.6 Hz, 1H), 2.78−2.58 (m, 2H), 2.29−2.07 (m, 2H), 1.75−1.65
(m, 2H), 1.58 (s, 1H). 13C{1H} NMR (151 MHz, CDCl3) δ 141.0,
133.5, 127.4, 127.3, 124.8, 117.3, 68.9, 41.0, 37.4, 31.0. HRMS (ESI)
calcd for C12H16O ([M + H]+) m/z 177.1274, found 177.1274.
4.4.13. (R)-1-Phenylpent-4-en-2-ol (14). Colorless oil in 93% yield.
Enantiomeric excess was determined by HPLC with a Chiralcel OD-
H column (hexane/iPrOH = 97/3, 0.5 mL/min), tminor = 16.77 min,
+22.01 (c = 0.15, MeOH). The absolute configuration was
1
determined by analogy. H NMR (600 MHz, CDCl3) δ 7.30 (dd, J
= 28.5, 8.5 Hz, 4H), 5.77 (ddd, J = 17.0, 10.7, 8.4 Hz, 1H), 5.25−5.16
(m, 2H), 4.34 (d, J = 7.8 Hz, 1H), 2.49−2.37 (m, 1H), 2.17 (s, 1H),
0.87 (d, J = 6.8 Hz, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 140.9,
140.1, 133.3, 128.3, 128.2, 117.2, 77.1, 46.3, 16.4. HRMS (ESI) calcd
for C11H13ClO ([M + Na]+) m/z 219.0547, found 219.0548.
4.5.3. (1R,2R)-1-(4-Bromophenyl)-2-methylbut-3-en-1-ol (19).
Colorless oil in 93% yield. Enantiomeric excess was determined by
HPLC with a Chiralcel OD-H column (hexane/iPrOH = 99/1, 1.0
t
major = 22.07 min; ee = 95%. [α]D24 = −14.03 (c = 1.0, CHCl3). The
25
mL/min), tminor = 20.299 min, tmajor = 20.823 min; ee = 99%. [α]D
=
reported value21 for the R-enantiomer (97% ee) is [α]D= −14.24 (c =
+39.78 (c = 0.85, MeOH). The absolute configuration was
1
0.65, CHCl3). H NMR (600 MHz, CDCl3) δ 7.32−7.26 (m, 2H),
1
determined by analogy. H NMR (400 MHz, CDCl3) δ 7.40 (d, J
7.23−7.18 (m, 3H), 5.92−5.75 (m, 1H), 5.20−5.05 (m, 2H), 3.85 (tt,
J = 7.7, 4.8 Hz, 1H), 2.75 (ddd, J = 21.6, 13.6, 6.4 Hz, 2H), 2.35−2.13
(m, 2H), 1.81 (s, 1H). 13C{1H} NMR (151 MHz, CDCl3) δ 137.3,
133.6, 128.4, 127.5, 125.4, 117.1, 70.6, 42.2, 40.1. HRMS (ESI) calcd
for C11H14O ([M + Na]+) m/z 185.0937, found 185.0936.
= 8.4 Hz, 2H), 7.14 (d, J = 8.3 Hz, 2H), 5.76−5.61 (m, 1H), 5.17−
5.07 (m, 2H), 4.25 (d, J = 7.7 Hz, 1H), 2.40−2.29 (m, 1H), 2.12 (s,
1H), 0.80 (d, J = 6.8 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ
140.3, 139.1, 130.3, 127.5, 120.4, 116.3, 76.1, 45.3, 15.3. HRMS (ESI)
calcd for C11H13BrO ([M + Na]+) m/z 263.0042, found 263.0043.
4.5.4. 4-((1R,2R)-1-Hydroxy-2-methylbut-3-en-1-yl)benzonitrile
(20). Colorless oil in 97% yield. Enantiomeric excess was determined
4.4.14. (R)-1-Benzyloxy-pent-4-en-2-ol (15). Colorless oil in 96%
yield. Enantiomeric excess was determined by HPLC with a Chiralpak
AS-H column (hexane/iPrOH = 97/3, 0.5 mL/min), tminor = 20.67
min, tmajor = 23.57 min; ee = 93%. [α]D24 = −2.76 (c = 1.15, CHCl3).
The reported value22 for the S-enantiomer (53% ee) is [α]D = +0.9 (c
by HPLC with a Chiralpak AD-H column (hexane/iPrOH = 95/5, 1.0
25
mL/min), tmajor = 14.132 min, tminor = 20.221 min; ee = 99%. [α]D
=
+15.39 (c = 1.50, MeOH). The absolute configuration was
1
= 2.5, CHCl3). H NMR (600 MHz, CDCl3) δ 7.34−7.19 (m, 5H),
1
determined by analogy. H NMR (400 MHz, CDCl3) δ 7.59−7.54
5.76 (ddt, J = 17.2, 10.2, 7.1 Hz, 1H), 5.05 (dd, J = 23.1, 5.9 Hz, 2H),
4.49 (s, 2H), 3.82 (ddd, J = 13.5, 6.7, 3.4 Hz, 1H), 3.45 (dd, J = 9.5,
3.4 Hz, 1H), 3.31 (dd, J = 9.5, 7.5 Hz, 1H), 2.20 (t, J = 6.8 Hz, 2H).
13C{1H} NMR (151 MHz, CDCl3) δ 138.0, 134.2, 128.4, 127.8,
127.7, 117.7, 73.9, 73.4, 69.7, 37.9. HRMS (ESI) calcd for C12H16O2
([M + H]+) m/z 193.1223, found 193.1223.
(m, 2H), 7.38 (d, J = 8.1 Hz, 2H), 5.66 (ddd, J = 17.1, 10.4, 8.2 Hz,
1H), 5.16−5.07 (m, 2H), 4.38 (d, J = 7.1 Hz, 1H), 2.36 (dt, J = 14.2,
7.1 Hz, 1H), 2.27 (d, J = 2.4 Hz, 1H), 0.84 (d, J = 6.8 Hz, 3H).
13C{1H} NMR (101 MHz, CDCl3) δ 146.7, 138.3, 131.0, 126.5,
117.8, 116.8, 110.3, 75.9, 45.3, 15.2. HRMS (ESI) calcd for
C12H13NO ([M + Na]+) m/z 210.0889, found 210.0880.
4.4.15. (R)-1-Cyclohexyl-but-3-en-1-ol (16). Colorless oil in 92%
yield. Enantiomeric excess was determined by the formation of 3,5-
dinitrobenzoate ester of the title compound followed by HLPC with a
Chiralcel OD-H column (hexane/iPrOH = 95/5, 1.0 mL/min), tmajor
4.5.5. (1R,2R)-1-(4-Methoxyphenyl)-2-methylbut-3-en-1-ol (21).
Colorless oil in 91% yield. Enantiomeric excess was determined by
HPLC with a Chiralcel OJ-H column (hexane/iPrOH = 95/5, 1.0
25
24
mL/min), tmajor = 17.316 min, tminor = 20.829 min; ee = 99%. [α]D
=
= 9.970 min, tminor = 10.666 min; ee = 87%. [α]D = +3.9 (c = 1.0,
1
+42.4 (c = 1.5, CDCl3). The absolute configuration was determined
by analogy. 1H NMR (600 MHz, CDCl3) δ 7.26−7.24 (m, 2H),
6.90−6.85 (m, 2H), 5.81 (ddd, J = 17.2, 10.3, 8.2 Hz, 1H), 5.25−5.09
(m, 2H), 4.30 (d, J = 8.0 Hz, 1H), 3.80 (s, 3H), 2.46 (dt, J = 14.3, 7.1
Hz, 1H), 1.92 (s, 1H), 0.85 (d, J = 6.8 Hz, 3H). 13C{1H} NMR (151
MHz, CDCl3) δ 159.1, 140.9, 134.6, 127.9, 116.5, 113.6, 77.5, 55.2,
46.3, 16.5. HRMS (ESI) calcd for C12H16O2 ([M + Na]+) m/z
215.11033, found 215.1035.
CH2Cl2). The absolute configuration was determined by analogy. H
NMR (600 MHz, CDCl3) δ 5.84−5.68 (m, 1H), 5.12−4.99 (m, 2H),
3.33 (ddd, J = 9.1, 5.8, 3.5 Hz, 1H), 2.33−2.19 (m, 1H), 2.06 (dt, J =
14.0, 8.5 Hz, 1H), 1.79 (d, J = 12.8 Hz, 1H), 1.65 (dd, J = 53.1, 2.6
Hz, 4H), 1.50 (s, 1H), 1.20−0.92 (m, 6H). 13C{1H} NMR (151
MHz, CDCl3) δ 134.4, 116.9, 73.7, 42.0, 37.8, 28.0, 27.1, 25.5, 25.2,
25.1. HRMS (ESI) calcd for C10H18O ([M + Na]+) m/z 177.1250,
found 177.1250.
4.5. General Procedure for the Substituted Allylation of
Benzaldehyde with B3−B8. A screw-cap reaction tube with a stir
bar and 4 Å MS (50 mg) was evacuated, flame-dried, and back-filled
with argon. To this tube were added the (R)-TRIP-PA catalyst PA1
(2 mol %), freshly distilled benzaldehyde (0.10 mmol), and 1.0 mL of
dry toluene as a solvent. The reaction mixture was then cooled to −30
°C, followed by the addition of boronate B3−B8 (0.12 mmol),
dropwise over 30 s. The mixture was stirred 6 h at this temperature.
Then, 1 mL of 1 M HCl was added and the reaction mixture was
stirred for 15 min. Proton NMR of the crude mixture was collected
for dr analysis, and then the product was purified by flash
chromatography using ethyl acetate and hexanes (1:9).
4.5.6. Methyl 4-((1R,2R)-1-Hydroxy-2-methylbut-3-en-1-yl)-
benzoate (22). Colorless oil in 94% yield. Enantiomeric excess was
determined by HPLC with a Chiralcel OD-H column (hexane/iPrOH
= 95/5, 1.0 mL/min), tmajor = 13.187 min, tminor = 18.128 min; ee =
25
99%. [α]D = +25.2 (c = 0.95, MeOH). The absolute configuration
1
was determined by analogy. H NMR (400 MHz, CDCl3) δ 7.96−
7.92 (m, 2H), 7.33 (d, J = 8.2 Hz, 2H), 5.69 (ddd, J = 17.8, 9.7, 8.2
Hz, 1H), 5.19−5.03 (m, 2H), 4.37 (dd, J = 7.5, 2.5 Hz, 1H), 3.84 (s,
3H), 2.41 (dt, J = 14.6, 7.2 Hz, 1H), 2.21 (d, J = 1.4 Hz, 1H), 0.82 (d,
J = 6.8 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 165.8, 146.5,
138.9, 128.5, 128.4, 125.8, 116.3, 51.1, 45.3, 15.3. HRMS (ESI) calcd
for C13H16O3 ([M + Na]+) m/z 243.0992, found 243.0990.
K
https://dx.doi.org/10.1021/acs.joc.0c01646
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
4.5.7. (1R,2R)-2-Methyl-1-(naphthalen-2-yl)but-3-en-1-ol (23).
Colorless oil in 94% yield. Enantiomeric excess was determined by
2H), 4.37 (t, J = 5.7 Hz, 1H), 2.56−2.43 (m, 1H), 1.96 (d, J = 5.4 Hz,
1H), 1.13 (d, J = 6.8 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ
138.2, 130.7, 127.4, 127.2, 121.5, 115.8, 87.4, 84.7, 65.6, 43.5, 14.3.
HRMS (ESI) calcd for C13H14O ([M + Na]+) m/z 209.0937, found
209.0932.
HPLC with a Chiralcel OD-H column (hexane/iPrOH = 90/10, 1.0
25
mL/min), tminor = 11.641 min, tmajor = 12.893 min; ee = 99%. [α]D
=
+19.04 (c = 1.14, MeOH). The absolute configuration was
1
determined by analogy. H NMR (400 MHz, CDCl3) δ 7.75 (dd, J
4.5.13. (1S,2R)-1-Cyclohexyl-2-methylbut-3-en-1-ol (29). Color-
= 16.0, 13.9 Hz, 4H), 7.45−7.35 (m, 3H), 5.78 (ddd, J = 17.3, 10.2,
8.2 Hz, 1H), 5.21−5.11 (m, 2H), 4.46 (d, J =7.8 Hz, 1H), 2.60−2.47
(m, 1H), 2.19 (s, 1H), 0.83 (d, J = 6.8 Hz, 3H). 13C{1H} NMR (101
MHz, CDCl3) δ 139.5, 138.8, 132.1, 132.0, 127.0, 126.9, 126.6, 125.0,
124.9, 124.7, 123.6, 116.0, 76.9, 45.2, 15.6. HRMS (ESI) calcd for
C15H16O ([M + Na]+) m/z 235.1093, found 235.1088.
less oil in 90% yield. Enantiomeric excess was determined according
25
to its ester derivative 30. ee = 91%. [α]D = +19.48 (c = 0.55,
CHCl3). The reported value23 for the S,R-enantiomer (98% ee) is
24
1
[α]D = +18.4 (c = 1.29, CHCl3). H NMR (600 MHz, CDCl3) δ
5.84−5.71 (m, 1H), 5.17−5.02 (m, 2H), 3.10 (t, J = 5.8 Hz, 1H),
2.44−2.32 (m, 1H), 1.84−1.73 (m, 3H), 1.68−1.60 (m, 2H), 1.48 (s,
1H), 1.40 (dddd, J = 11.7, 8.9, 6.0, 2.7 Hz, 1H), 1.27−1.06 (m, 5H),
1.03 (d, J = 6.9 Hz, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 139.3,
115.1, 77.8, 39.5, 39.2, 29.0, 25.9, 25.4, 25.4, 25.1, 15.9. HRMS (ESI)
calcd for C11H20O ([M + Na]+) m/z 191.1406, found 191.1399.
4.5.14. (1S,2R)-1-Cyclohexyl-2-methylbut-3-en-1-yl 3,5-dinitro-
benzoate (30). White solid in 71% yield. mp = 68−69 °C.
Enantiomeric excess was determined by HPLC with a Chiralcel IB
N-5 column (hexane/iPrOH = 99/1, 1.0 mL/min), tmajor = 14.145
min, tminor = 15.182 min; ee = 91%. [α]D25 = +6.41 (c = 0.45, MeOH).
1H NMR (600 MHz, CDCl3) δ 9.16 (t, J = 2.1 Hz, 1H), 9.07 (d, J =
4.5.8. (1R,2R)-2-Methyl-1-(naphthalen-1-yl)but-3-en-1-ol (24).
Colorless oil in 93% yield. Enantiomeric excess was determined by
HPLC with a Chiralcel OD-H column (hexane/iPrOH = 90/10, 1.0
25
mL/min), tminor = 8.326 min, tmajor = 17.596 min; ee = 97%. [α]D
=
+25.38 (c = 0.84, MeOH). The absolute configuration was
1
determined by analogy. H NMR (600 MHz, CDCl3) δ 8.15 (d, J
= 8.4 Hz, 1H), 7.86−7.83 (m, 1H), 7.75 (t, J = 7.9 Hz, 1H), 7.54 (d, J
= 7.1 Hz, 1H), 7.50−7.41 (m, 3H), 5.86 (ddd, J = 16.9, 10.7, 7.8 Hz,
1H), 5.18−5.12 (m, 3H), 2.80 (h, J = 6.9 Hz, 1H), 2.28 (s, 1H), 0.94
(d, J = 6.9 Hz, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 140.2,
138.4, 133.9, 131.0, 128.9, 128.1, 125.8, 125.4, 125.2, 124.5, 123.6,
116.7, 74.8, 45.2, 17.1. HRMS (ESI) calcd for C15H16O ([M + Na]+)
m/z 235.1093, found 235.1084.
2.1 Hz, 2H), 5.73 (ddd, J = 17.1, 10.2, 8.6 Hz, 1H), 5.03−4.95 (m,
3H), 2.72−2.53 (m, 1H), 1.72−1.59 (m, 6H), 1.23−1.08 (m, 5H),
0.99 (d, J = 6.9 Hz, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 161.3,
147.7, 137.9, 133.2, 128.3, 121.2, 115.2, 98.9, 82.7, 38.4, 38.0, 28.6,
26.7, 25.1, 24.9, 24.7, 16.3. HRMS (ESI) calcd for C18H22N2O6 ([M +
Na]+) m/z 385.1370, found 385.1362.
4.5.9. (1R,2R)-1-(Anthracen-9-yl)-2-methylbut-3-en-1-ol (25).
Yellow solid in 92% yield. mp = 121−122 °C. Enantiomeric excess
was determined by HPLC with a Chiralpak AD-H column (hexane/
iPrOH = 95/5, 1.0 mL/min), tminor = 20.571 min, tmajor = 23.962 min;
4.5.15. (R)-2,2-Dimethyl-1-phenylbut-3-en-1-ol (31). Colorless oil
in 97% yield. Enantiomeric excess was determined by HPLC with a
Chiralcel OD-H column (hexane/iPrOH = 90/10, 1.0 mL/min),
25
ee = 93%. [α]D = +12.59 (c = 2.25, MeOH). The absolute
configuration was determined by analogy. 1H NMR (600 MHz,
CDCl3) δ 8.57 (s, 1H), 8.31 (d, J = 13.5 Hz, 2H), 7.91 (d, J = 8.2 Hz,
2H), 7.52−7.26 (m, 4H), 6.04 (ddd, J = 17.4, 10.1, 8.3 Hz, 1H), 5.85
(d, J = 10.0 Hz, 1H), 5.34 (d, J = 17.2 Hz, 1H), 5.24 (dd, J = 10.2, 1.2
Hz, 1H), 3.36−3.24 (m, 1H), 2.41 (s, 1H), 0.56 (d, J = 6.8 Hz, 3H).
13C{1H} NMR (151 MHz, CDCl3) δ 141.0, 131.7, 130.6, 129.2,
128.3, 127.3, 124.5, 123.7, 115.6, 72.6, 44.4, 16.3. HRMS (ESI) calcd
for C19H18O ([M + Na]+) m/z 285.1250, found 285.1249.
t
minor = 5.150 min, tmajor = 6.786 min; ee = 99%. [α]D25 = +7.096 (c =
1.55, MeOH). The absolute configuration was determined by analogy.
1H NMR (600 MHz, CDCl3) δ 7.25−7.16 (m, 5H), 5.84 (dd, J =
17.5, 10.8 Hz, 1H), 5.04 (dd, J = 38.2, 14.1 Hz, 2H), 4.35 (s, 1H),
1.91 (s, 1H), 0.94 (s, 3H), 0.89 (s, 3H). 13C{1H} NMR (151 MHz,
CDCl3) δ 144.0, 139.6, 126.7, 126.4, 126.3, 112.8, 79.5, 41.2, 23.4,
19.9. HRMS (ESI) calcd for C12H16O ([M + H]+) m/z 177.1274,
found 177.1274.
4.5.10. (1R,2R)-2-Methyl-1-(thiophen-2-yl)but-3-en-1-ol (26).
Colorless oil in 93% yield. Enantiomeric excess was determined by
4.5.16. (1R,2R)-2,6-Dimethyl-1-phenyl-2-vinylhept-5-en-1-ol
(32). Colorless oil in 92% yield. Enantiomeric excess was determined
HPLC with a Chiralcel OJ-H column (hexane/iPrOH = 96/4, 1.0
25
mL/min), tminor = 10.043 min, tmajor = 10.569 min; ee = 99%. [α]D
=
by HPLC with a Chiralpak AD-H column (hexane/iPrOH = 98/2, 1.0
25
+11.23 (c = 0.77, MeOH). The absolute configuration was
mL/min), tminor = 9.570 min, tmajor = 10.661 min; ee = 77%. [α]D
=
+13.83 (c = 1.50, EtOH). The reported value24 for the S,S-enantiomer
(94% ee) is [α]D24 = −12.32 (c = 1.16, EtOH). 1H NMR (600 MHz,
CDCl3) δ 7.29−7.23 (m, 5H), 5.84 (dd, J = 17.6, 10.8 Hz, 1H), 5.25
(dd, J = 10.8, 1.3 Hz, 1H), 5.11−5.00 (m, 2H), 4.39 (d, J = 5.8 Hz,
1H), 2.09 (s, 1H), 1.85 (dd, J = 16.2, 7.9 Hz, 2H), 1.65 (s, 3H), 1.54
(s, 3H), 1.44−1.22 (m, 2H), 0.91 (s, 3H). 13C{1H} NMR (151 MHz,
CDCl3) δ 143.9, 140.5, 131.2, 128.1, 127.5, 127.4, 124.7, 115.8, 80.0,
45.9, 37.5, 25.6, 22.8, 17.6, 16.2. HRMS (ESI) calcd for C17H24O ([M
+ Na]+) m/z 267.1713, found 267.1719.
1
determined by analogy. H NMR (600 MHz, CDCl3) δ 7.27−7.26
(m, 1H), 6.99−6.95 (m, 2H), 5.83 (ddd, J = 17.3, 10.3, 8.1 Hz, 1H),
5.26−5.18 (m, 2H), 4.66 (d, J = 7.7 Hz, 1H), 2.55 (dt, J = 14.6, 7.3
Hz, 1H), 2.25 (s, 1H), 0.96 (d, J = 6.8 Hz, 3H). 13C{1H} NMR (151
MHz, CDCl3) δ 146.3, 140.0, 126.4, 124.7, 117.2, 73.9, 46.6, 16.5.
HRMS (ESI) calcd for C9H12OS ([M + Na]+) m/z 191.0501, found
191.0498.
4.5.11. (3S,4R,E)-4-Methyl-1-phenylhexa-1,5-dien-3-ol (27). Col-
orless oil in 92% yield. Enantiomeric excess was determined by HPLC
with a Chiralcel OD-H column (hexane/iPrOH = 90/10, 1.0 mL/
min), tmajor = 7.074 min, tminor = 9.823 min; ee = 95%. [α]D25 = +13.90
(c = 1.09, MeOH). The absolute configuration was determined by
4.5.17. (1R,2S)-2,6-Dimethyl-1-phenyl-2-vinylhept-5-en-1-ol
(33). Colorless oil in 87% yield. Enantiomeric excess was determined
by HPLC with a Chiralpak AD-H column (hexane/iPrOH = 98/2, 1.0
25
1
mL/min), tminor = 9.793 min, tmajor= 11.241 min; ee = 95%. [α]D
=
analogy. H NMR (400 MHz, CDCl3) δ 7.39 (dd, J = 9.3, 2.2 Hz,
−5.58 (c = 1.15, EtOH). The reported value24 for the S,R-enantiomer
2H), 7.32 (dd, J = 10.2, 4.8 Hz, 2H), 7.24 (dd, J = 5.8, 3.6 Hz, 1H),
6.65−6.53 (m, 1H), 6.21 (dd, J = 15.9, 7.0 Hz, 1H), 5.87−5.75 (m,
1H), 5.23−5.17 (m, 1H), 5.16 (d, J = 0.8 Hz, 1H), 4.05 (t, J = 6.5 Hz,
1H), 2.37 (dd, J = 13.9, 7.7 Hz, 1H), 1.68 (s, 1H), 1.07 (t, J = 4.9 Hz,
3H). 13C{1H} NMR (101 MHz, CDCl3) δ 140.1, 136.7, 131.7, 130.2,
128.5, 127.6, 126.5, 116.6, 76.1, 44.6, 16.0. HRMS (ESI) calcd for
C13H16O ([M + Na]+) m/z 211.1093, found 211.1086.
24
1
(98% ee) is [α]D = +4.33 (c = 1.05, EtOH). H NMR (600 MHz,
CDCl3) δ 7.25−7.19 (m, 5H), 5.72 (dd, J = 17.6, 10.9 Hz, 1H), 5.13
(d, J = 10.8 Hz, 1H), 4.95 (d, J = 17.5 Hz, 2H), 4.37 (d, J = 10.0 Hz,
1H), 1.80 (ddd, J = 28.6, 14.5, 7.1 Hz, 3H), 1.58 (s, 3H), 1.48 (s,
3H), 1.31−1.26 (m, 2H), 1.01 (s, 3H). 13C{1H} NMR (151 MHz,
CDCl3) δ 141.6, 140.1, 130.1, 126.8, 126.4, 126.3, 123.7, 114.2, 79.7,
44.2, 35.3, 24.6, 21.7, 17.9, 16.6. HRMS (ESI) calcd for C17H24O ([M
+ Na]+) m/z 267.1719, found 267.1713.
4.5.12. (3R,4R)-4-Methyl-1-phenylhex-5-en-1-yn-3-ol (28). Color-
less oil in 91% yield. Enantiomeric excess was determined by HPLC
with a Chiralpak AS-H column (hexane/iPrOH = 98/2, 1.0 mL/min),
4.5.18. (1R,2R)-1-Phenyl-2-vinylpentan-1-ol (34). Colorless oil in
97% yield. Enantiomeric excess was determined by HPLC with a
Chiralpak AD-H column (hexane/iPrOH = 98/2, 1.0 mL/min), tminor
t
major = 12.498 min, tminor = 15.472 min; ee = 99%. [α]D25 = +15.26 (c
= 0.55, MeOH). The absolute configuration was determined by
1
25
analogy. H NMR (400 MHz, CDCl3) δ 7.46−7.33 (m, 2H), 7.31−
= 10.884 min, tmajor = 11.443 min; ee = 91%. [α]D = +21.45 (c =
7.19 (m, 3H), 5.91−5.72 (m, 1H), 5.13 (ddt, J = 6.4, 2.5, 1.6 Hz,
0.85, MeOH). The absolute configuration was determined by analogy.
L
https://dx.doi.org/10.1021/acs.joc.0c01646
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
1H NMR (600 MHz, CDCl3) δ 7.28−7.19 (m, 5H), 5.62−5.55 (m,
1H), 5.20−5.08 (m, 2H), 4.31 (d, J = 7.8 Hz, 1H), 2.23 (dt, J = 13.6,
6.2 Hz, 1H), 2.11 (s, 1H), 1.27−1.05 (m, 4H), 0.71 (t, J = 7.2 Hz,
3H). 13C{1H} NMR (151 MHz, CDCl3) δ 142.5, 139.4, 128.2, 127.6,
127.0, 118.7, 52.5, 32.5, 20.3, 13.9. HRMS (ESI) calcd for C13H18O
([M + Na]+) m/z 213.1250, found 213.1241.
4.6.5. (R)-1-(3-Methoxy-phenyl)-but-3-yn-1-ol (40). Colorless oil
in 96% yield. Enantiomeric excess was determined by HPLC with a
Chiralcel OD-H column (hexane/iPrOH = 98/2, 1.0 mL/min), tmajor
25
= 36.16 min, tminor = 41.49 min; ee = 96%. [α]D = +7.39 (c = 0.59,
1
CHCl3). The absolute configuration was determined by analogy. H
NMR (600 MHz, CDCl3) δ 7.21 (d, J = 7.9 Hz, 1H), 6.92−6.86 (m,
2H), 6.77 (d, J = 7.2 Hz, 1H), 4.78 (t, J = 6.3 Hz, 1H), 3.74 (s, 3H),
2.57 (dd, J = 6.7, 2.7 Hz, 2H), 2.32 (s, 1H), 2.01 (t, J = 2.6 Hz, 1H).
13C{1H} NMR (151 MHz, CDCl3) δ 158.7, 143.1, 128.5, 117.0,
112.4, 110.2, 79.6, 71.2, 69.9, 54.2, 28.4. HRMS (ESI) calcd for
C11H12O2 ([M + H]+) m/z 177.0910, found 177.0909.
4.5.19. (R)-((R)-Cyclohex-2-en-1-yl)(phenyl)methanol (35). Color-
less oil in 94% yield. Enantiomeric excess was determined by HPLC
with a Chiralpak AD-H column (hexane/iPrOH = 90/10, 1.0 mL/
min), tmajor = 6.273 min, tminor = 6.518 min; ee = 23%. [α]D25 = +11.54
(c = 0.85, CH2Cl2). The absolute configuration was determined by
1
analogy. H NMR (600 MHz, CDCl3) δ 7.30−7.19 (m, 5H), 5.75
4.6.6. (R)-1-o-Tolyl-but-3-yn-1-ol (41). Colorless oil in 94% yield.
Enantiomeric excess was determined by HPLC with a Chiralpak AD-
H column (hexane/iPrOH = 98/2, 1.0 mL/min), tmajor = 16.07 min,
(ddd, J = 9.8, 6.1, 3.4 Hz, 1H), 5.32 (dd, J = 10.2, 1.9 Hz, 1H), 4.53
(d, J = 6.5 Hz, 1H), 2.44 (ddq, J = 11.3, 5.8, 2.7 Hz, 1H), 1.92 (t, J =
6.6 Hz, 2H), 1.70−1.62 (m, 2H), 1.53 (s, 1H), 1.46 (dt, J = 18.0, 6.2
Hz, 2H). 13C{1H} NMR (151 MHz, CDCl3) δ 141.8, 129.4, 127.2,
126.9, 126.3, 125.4, 76.3, 41.9, 24.1, 22.7, 20.0. HRMS (ESI) calcd for
C13H16O ([M + Na]+) m/z 211.1093, found 211.1098.
t
minor = 20.40 min; ee = 93%. [α]D25 = +34.97 (c = 1.0, CHCl3). The
reported value26 for the S-enantiomer (89% ee) is [α]D25 = −63.2 (c =
1
0.58, CHCl3). H NMR (600 MHz, CDCl3) δ 7.44 (d, J = 7.5 Hz,
1H), 7.18−7.05 (m, 3H), 5.05 (dd, J = 7.7, 5.0 Hz, 1H), 2.58−2.49
(m, 2H), 2.29 (s, 3H), 2.02 (t, J = 2.6 Hz, 1H). 13C{1H} NMR (151
MHz, CDCl3) δ 139.4, 133.5, 129.4, 126.7, 125.3, 124.0, 79.9, 69.7,
67.8, 27.2, 18.0. HRMS (ESI) calcd for C11H12O ([M + H]+) m/z
161.0961, found 161.0960.
4.6. General Procedure for the Propargylation of Alde-
hydes. A screw-cap reaction tube loaded with a stir bar and 4 Å MS
(50 mg) was evacuated, flame-dried, and back-filled with argon. To
this tube were added the (R)-TRIP-PA catalyst PA1 (5 mol %),
freshly distilled aldehyde (0.1 mmol), and 1.0 mL of dry cyclohexane.
Then, allenylboronic acid ester B10 (0.12 mmol) was added via a
syringe to the reaction mixture dropwise over 30 s. The reaction
mixture was stirred for 8 h at room temperature and then directly
loaded onto a silica gel column and was purified by flash
chromatography using ethyl acetate and hexane (1:9).
4.6.7. (R)-Methyl 4-(1-hydroxybut-3ynyl)benzoate (42). Colorless
oil in 96% yield. Enantiomeric excess was determined by HPLC with a
Chiralcel OD-H column (hexane/iPrOH = 90/10, 1.0 mL/min), tmajor
= 11.88 min, tminor = 16.97 min; ee = 97%. [α]D25 = +34.56 (c = 1.08,
1
CHCl3). The absolute configuration was determined by analogy. H
NMR (600 MHz, CDCl3) δ 7.95 (d, J = 8.3 Hz, 2H), 7.39 (d, J = 8.2
Hz, 2H), 4.92−4.78 (m, 1H), 3.84 (s, 3H), 2.62−2.53 (m, 2H), 2.37
(s, 1H), 2.01 (t, J = 2.6 Hz, 1H). 13C{1H} NMR (151 MHz, CDCl3)
δ 165.8, 146.3, 128.7, 124.7, 79.0, 70.8, 70.4, 51.1, 28.4. HRMS (ESI)
calcd for C12H12O3 ([M + H]+) m/z 205.0859, found 205.0860.
4.6.8. (R)-1-(Benzo[d][1,3]dioxol-5-yl)but-3-yn-1-ol (43). Color-
less oil in 94% yield. Enantiomeric excess was determined by HPLC
with a Chiralcel OD-H column (hexane/iPrOH = 95/5, 1.0 mL/
min), tmajor = 15.89 min, tminor = 22.40 min; ee = 95%. [α]D25 = +3.89
(c = 1.49, CHCl3). The absolute configuration was determined by
analogy. 1H NMR (600 MHz, CDCl3) δ 6.77 (ddd, J = 35.9, 35.2, 4.7
Hz, 3H), 5.89 (s, 2H), 4.73 (t, J = 6.4 Hz, 1H), 2.57−2.50 (m, 2H),
2.24 (s, 1H), 2.01 (t, J = 2.6 Hz, 1H). 13C{1H} NMR (151 MHz,
CDCl3) δ 146.7, 146.2, 135.5, 118.2, 107.1, 105.2, 100.0, 79.5, 71.2,
70.0, 28.5. HRMS (ESI) calcd for C11H10O3 ([M + H]+) m/z
191.0703, found 191.0701.
4.6.9. (R)-1-Thiophen-2-yl-but-3-yn-1-ol (44). Colorless oil in 95%
yield. Enantiomeric excess was determined by HPLC with a Chiralcel
OJ-H column (hexane/iPrOH = 90/10, 1.0 mL/min), tminor = 16.64
min, tmajor = 18.13 min; ee = 91%. [α]D25 = −19.42 (c = 1.54, EtOH).
The absolute configuration was determined by analogy. 1H NMR
(600 MHz, CDCl3) δ 7.27 (d, J = 6.1 Hz, 1H), 7.07−6.93 (m, 2H),
5.17−5.07 (m, 1H), 2.78−2.74 (m, 2H), 2.49 (d, J = 3.2 Hz, 1H),
2.11 (t, J = 2.6 Hz, 1H). 13C{1H} NMR (151 MHz, CDCl3) δ 145.1,
125.6, 123.9, 123.1, 79.0, 70.5, 67.5, 28.5. HRMS (ESI) calcd for
C8H8OS ([M + H]+) m/z 153.0369, found 153.0367.
4.6.10. (R,E)-1-Phenylhex-1-en-5-yn-3-ol (45). Colorless oil in
94% yield. Enantiomeric excess was determined by HPLC with a
Chiralcel OD-H column (hexane/iPrOH = 90/10, 1.0 mL/min), tmajor
= 9.51 min, tminor = 13.17 min; ee = 91%. [α]D25 = −49.32 (c = 0.62,
benzene). The absolute configuration was determined by analogy. 1H
NMR (600 MHz, CDCl3) δ 7.32 (d, J = 7.3 Hz, 2H), 7.25 (t, J = 7.6
Hz, 2H), 7.18 (d, J = 8.5 Hz, 1H), 6.59 (d, J = 15.9 Hz, 1H), 6.21
(dd, J = 15.9, 6.3 Hz, 1H), 4.41 (q, J = 5.9 Hz, 1H), 2.54−2.43 (m,
2H), 2.08 (s, 1H), 2.02 (t, J = 2.6 Hz, 1H). 13C{1H} NMR (151
MHz, CDCl3) δ 135.3, 130.3, 128.9, 127.5, 127.1, 126.8, 125.5, 79.1,
70.1, 69.7, 26.7. HRMS (ESI) calcd for C12H12O ([M + H]+) m/z
173.0961, found 173.0961.
4.6.1. (R)-1-Phenyl-but-3-yn-1-ol (36). Colorless oil in 94% yield.
Enantiomeric excess was determined by HPLC with a Chiralcel OD-
H column (hexane/iPrOH = 95/5, 1.0 mL/min), tmajor = 10.40 min,
t
minor = 12.37 min; ee = 97%. [α]D25 = +12.29 (c = 1.14, MeOH). The
reported value25 for the R-enantiomer (98% ee) is [α]D24 = +12.9 (c =
1
1.55, MeOH). H NMR (600 MHz, CDCl3) δ 7.43−7.28 (m, 5H),
4.88 (t, J = 6.4 Hz, 1H), 2.68−2.61 (m, 2H), 2.37 (s, 1H), 2.08 (t, J =
2.6 Hz, 1H). 13C{1H} NMR (151 MHz, CDCl3) δ 141.4, 127.4,
127.0, 124.7, 79.6, 71.3, 69.9, 28.4. HRMS (ESI) calcd for C10H10O
([M + H]+) m/z 147.0804, found 147.0803.
4.6.2. (R)-1-(4-Bromo-phenyl)-but-3-yn-1-ol (37). Colorless oil in
94% yield. Enantiomeric excess was determined by HPLC with a
Chiralcel OD-H column (hexane/iPrOH = 98/2, 1.0 mL/min), tmajor
= 20.57 min, tminor =23.23 min; ee = 99%. [α]D25 = +21.89 (c = 1.21,
CHCl3). The reported value26 for the S-enantiomer (81% ee) is [α]D
1
= −28.4 (c = 1, CHCl3). H NMR (600 MHz, CDCl3) δ 7.53−7.42
(m, 2H), 7.32−7.22 (m, 2H), 4.88−4.78 (m, 1H), 2.66−2.53 (m,
2H), 2.46 (s, 1H), 2.07 (t, J = 2.6 Hz, 1H). 13C{1H} NMR (151
MHz, CDCl3) δ 140.3, 130.5, 126.4, 120.8, 79.1, 70.6, 70.3, 28.4.
HRMS (ESI) calcd for C10H9BrO ([M + H]+) m/z 224.9910, found
224.9909.
4.6.3. (R)-1-(4-Nitro-phenyl)-but-3-yn-1-ol (38). Colorless oil in
93% yield. Enantiomeric excess was determined by HPLC with a
Chiralcel OJ-H column (hexane/iPrOH = 90/10, 1.0 mL/min), tminor
25
= 29.91 min, tmajor =33.41 min; ee = 97%. [α]D = +4.08 (c = 1.07,
1
CHCl3). The absolute configuration was determined by analogy. H
NMR (600 MHz, CDCl3) δ 8.22 (d, J = 8.7 Hz, 2H), 7.59 (d, J = 8.6
Hz, 2H), 5.00 (t, J = 5.8 Hz, 1H), 2.75−2.64 (m, 2H), 2.59 (s, 1H),
2.11 (t, J = 2.6 Hz, 1H). 13C{1H} NMR (151 MHz, CDCl3) δ 148.4,
146.5, 125.6, 122.6, 78.3, 70.9, 70.2, 28.5. HRMS (ESI) calcd for
C10H9NO3 ([M + H]+) m/z 192.0655, found 192.0654.
4.6.4. (R)-1-(4-Methoxy-phenyl)-but-3-yn-1-ol (39). Colorless oil
in 91% yield. Enantiomeric excess was determined by HPLC with a
Chiralcel OD-H column (hexane/iPrOH = 90/10, 1.0 mL/min), tmajor
25
= 8.72 min, tminor = 10.75 min; ee = 95%. [α]D = +34.74 (c = 1.45,
CHCl3). The reported value4g for the S-enantiomer (89% ee) is
[α]D28 = −36.2 (c = 1, CHCl3). 1H NMR (600 MHz, CDCl3) δ 7.25
(d, J = 8.6 Hz, 2H), 6.82 (d, J = 8.7 Hz, 2H), 4.77 (t, J = 6.4 Hz, 1H),
3.74 (s, 3H), 2.60−2.52 (m, 2H), 2.00 (t, J = 2.6 Hz, 1H). 13C{1H}
NMR (151 MHz, CDCl3) δ 158.3, 133.6, 126.0, 112.8, 79.8, 70.9,
69.8, 54.2, 28.3. HRMS (ESI) calcd for C11H12O2 ([M + H]+) m/z
177.0910, found 177.0909.
4.7. Procedures for Synthetic Application. Compound 47 was
prepared following the literature procedure15b with starting alcohol 19
with 99% ee, dr > 20:1.
4.7.1. (1S,2R)-1-(4-Bromophenyl)-2-methylbut-3-en-1-yl(S)-2-
((tert-butoxycarbonyl)amino)-3-hydroxy-3-methylbutanoate (47).
M
https://dx.doi.org/10.1021/acs.joc.0c01646
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
The title compound was obtained by flash column chromatography
(hexane/EA, 8: 1) as a colorless oil in 86% yield. Enantiomeric excess
was determined by HPLC with a Chiralpak IF column (hexane/
iPrOH = 80/20, 1.0 mL/min), tminor = 7.233 min, tmajor = 8.502 min;
Sci-Tech University, Hangzhou City, Zhejiang Province 310018,
China; Email: jantilla@tju.edu.cn
Authors
25
ee = 99%. [α]D = −2.54 (c = 0.75, MeOH). The absolute
Jinping Yuan − Institute for Molecular Design and Synthesis,
School of Pharmaceutical Science and Technology, Tianjin
University, Tianjin 300072, China
Pankaj Jain − Novartis Institutes for BioMedical Research,
Cambridge, Massachusetts 02139, United States
configuration was determined by analogy. 1H NMR (400 MHz,
CDCl3) δ 7.39−7.35 (m, 2H), 7.10 (t, J = 8.1 Hz, 2H), 5.64−5.43
(m, 2H), 5.31−5.20 (m, 1H), 5.02−4.83 (m, 2H), 4.21−4.07 (m,
1H), 2.59 (ddd, J = 86.5, 47.1, 31.8 Hz, 2H), 1.36 (d, J = 14.0 Hz,
9H), 1.18 (d, J = 7.1 Hz, 6H), 1.03−0.97 (m, 3H). 13C{1H} NMR
(101 MHz, CDCl3) δ 171.4, 155.6, 138.3, 137.1, 131.3, 129.0, 122.1,
116.5, 80.1, 79.6, 72.2, 71.8, 61.1, 42.6, 28.2, 27.0, 26.1, 21.6. HRMS
(ESI) calcd for C21H30BrNO5 ([M + Na]+) m/z 478.1200, found
478.1204.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c01646
Notes
Compounds 49 and 50 were prepared following the literature
procedure27 with starting alcohol 19 with 89% ee, dr > 20:1.
4.7.2. (1R,2R)-1-(4-Bromophenyl)-2-methylbut-3-en-1-yl acrylate
(49). The title compound was obtained by flash column
chromatography (hexane/EA = 10:1) as a colorless oil in 92%
yield. Enantiomeric excess was determined by HPLC with a Chiralcel
OJ-H column (hexane/iPrOH = 98/2, 1.0 mL/min), tmajor = 5.293
min, tminor = 8.161 min; ee = 87%. [α]D25 = +28.02 (c = 0.85, MeOH).
The absolute configuration was determined by analogy. 1H NMR
(600 MHz, CDCl3) δ 7.40−7.36 (m, 2H), 7.14−7.10 (m, 2H), 6.33
(dd, J = 17.3, 1.4 Hz, 1H), 6.06 (dd, J = 17.3, 10.4 Hz, 1H), 5.75 (dd,
J = 10.4, 1.4 Hz, 1H), 5.72−5.62 (m, 1H), 5.55 (d, J = 7.5 Hz, 1H),
4.99−4.93 (m, 2H), 2.60 (dt, J = 14.5, 7.2 Hz, 1H), 0.85 (d, J = 6.9
Hz, 3H). 13C{1H} NMR (151 MHz, CDCl3) δ 164.1, 138.0, 136.9,
130.3, 130.0, 127.7, 127.3, 120.8, 115.0, 77.5, 42.3, 15.1. HRMS (ESI)
calcd for C14H15BrO2 ([M + Na]+) m/z 317.0148, found 317.0144.
4.7.3. (5R,6R)-6-(4-Bromophenyl)-5-methyl-5,6-dihydro-2H-
pyran-2-one (50). The title compound was obtained by flash column
chromatography (hexane/EA = 2:1) as a white solid in 84% yield. mp
= 109−110 °C. Enantiomeric excess was determined by HPLC with a
Chiralpak AD-H column (hexane/iPrOH = 75/25, 1.0 mL/min),
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Our work has received financial support from the National
1000 Talent Plan of China and from Tianjin University for
start-up funds.
REFERENCES
■
(1) For reviews on allylations, propargylations and crotylations, see
(a) Roush, W. R. Comprehensive Organic Synthesis; Trost, B. M., Ed.;
Pergamon Press: Oxford, U.K., 1991; Vol. 2, pp 1−54. (b) Lachance,
H.; Hall, D. G. In Organic Reactions; Denmark, S. E., Ed.; John Wiley
& Sons, Inc., 2008; Vol. 73, pp 1−69. (c) Denmark, S. E.; Almstead,
N. G. In Modern Carbonyl Chemistry; Otera, J., Ed.; Wiley-VCH:
Weinheim, 2000; Chapter 10, pp 299−402. (d) Chemler, S. R.;
Roush, W. R. In Modern Carbonyl Chemistry; Otera, J., Ed.; Wiley-
VCH: Weinheim, 2000; Chapter 11, pp 403−490. (e) Brown, H. C.;
Racherla, U. S.; Liao, Y.; Khanna, V. V. Chiral synthesis via
organoboranes. 35. Simple procedures for the efficient recycling of
the terpenyl chiral auxiliaries and convenient isolation of the
homoallylic alcohols in asymmetric allyl- and crotylboration of
aldehydes. J. Org. Chem. 1992, 57, 6608−6614. (f) Denmark, S. E.;
Fu, J. Catalytic Enantioselective Addition of Allylic Organometallic
Reagents to Aldehydes and Ketones. Chem. Rev. 2003, 103, 2763−
2794. (g) Ding, C. H.; Hou, X. L. Catalytic Asymmetric
Propargylation. Chem. Rev. 2011, 111, 1914−1937. (h) Yus, M.;
t
major = 6.826 min, tminor = 7.334 min; ee = 82%. [α]D25 = +92.41 (c =
1.25, MeOH). The absolute configuration was determined by analogy.
1H NMR (400 MHz, CDCl3) δ 7.58−7.48 (m, 2H), 7.25 (d, J = 1.8
Hz, 2H), 6.74 (dd, J = 9.8, 2.1 Hz, 1H), 6.08 (dd, J = 9.8, 2.6 Hz,
1H), 4.94 (d, J = 10.8 Hz, 1H), 2.83−2.71 (m, 1H), 1.01 (d, J = 7.3
Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 162.6, 150.0, 135.3,
130.7, 128.0, 122.0, 119.4, 84.2, 34.2, 14.7. HRMS (ESI) calcd for
C12H11BrO2 ([M + Na]+) m/z 288.9835, found 288.9833.
4.8. General Procedure for Gram-Scale Reaction. The
reaction was conducted on a 10.0 mmol scale of benzaldehyde
according to the above general allylboration method. Boronate B2,
B3, and B10 were added to the reaction system over 2 h. The product
was purified by silica gel flash column chromatography (ethyl acetate/
hexane = 1:9) to afford desired product 51 (1.43 g, 97% yield, 99%
ee), 52 (2.13 g, 97% yield, 93% ee, dr > 20:1), and 53 (1.41 g, 97%
yield, 98% ee) as a colorless oil.
́
́
Gonzalez-Gomez, J. C.; Foubelo, F. Catalytic Enantioselective
Allylation of Carbonyl Compounds and Imines. Chem. Rev. 2011,
111, 7774−7854. (i) Yamamoto, Y.; Asao, N. Selective reactions using
allylic metals. Chem. Rev. 1993, 93, 2207−2293.
(2) (a) Meng, Z.; Souillart, L.; Monks, B.; Huwyler, N.; Herrmann,
̈ ̈
J.; Muller, R.; Furstner, A. A “Motif-Oriented” Total Synthesis of
Nannocystin Ax. Preparation and Biological Assessment of Analogues.
J. Org. Chem. 2018, 83, 6977−6994. (b) Felpin, F. X.; Lebreton, J. A
Highly Stereoselective Asymmetric Synthesis of (−)-Lobeline and
(−)-Sedamine. J. Org. Chem. 2002, 67, 9192−9199. (c) Felpin, F. X.;
Lebreton, J. Enantiospecific and stereoselective synthesis of
(−)-allosedamine. Tetrahedron Lett. 2002, 43, 225−227. (d) Hoff-
mann, R. W.; Ladner, W. On the absolute stereochemistry of C-2 and
C-3 in stegobinone. Tetrahedron Lett 1979, 20, 4653−4656. (e) Lu,
H. H.; Raja, A.; Franke, R.; Landsberg, D.; Sasse, F.; Kalesse, M.
Synthesis and Biological Evaluation of Paleo-Soraphens. Angew.
Chem., Int. Ed. 2013, 52, 13549−13552.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c01646.
■
sı
Experimental details; experimental preparations; charac-
terization; NMR spectra; chiral HPLC conditions; and
other data (PDF)
Crystallographic data for 30 (CIF)
CheckCIF/PLATON report (PDF)
(3) (a) Bhakta, U.; Sullivan, E.; Hall, D. G. Catalytic enantioselective
allylboration of propargylic aldehydes. Tetrahedron 2014, 70, 678−
683. (b) Corey, E. J.; Yu, C. M.; Kim, S. S. A practical and efficient
method for enantioselective allylation of aldehydes. J. Am. Chem. Soc.
1989, 111, 5495−5496. (c) Gravel, M.; Lachance, H.; Lu, X.; Hall, D.
G. Scope and Limitations of the Scandium-Catalyzed Enantioselective
Addition of Chiral Allylboronates to Aldehydes. Synthesis 2004, 2004,
1290−1302. (d) Ishiyama, T.; Ahiko, T. A.; Miyaura, N. Acceleration
Effect of Lewis Acid in Allylboration of Aldehydes: Catalytic,
Regiospecific, Diastereospecific, and Enantioselective Synthesis of
Homoallyl Alcohols. J. Am. Chem. Soc. 2002, 124, 12414−12415.
AUTHOR INFORMATION
Corresponding Author
■
Jon C. Antilla − Institute for Molecular Design and Synthesis,
School of Pharmaceutical Science and Technology, Tianjin
University, Tianjin 300072, China; School of Sciences, Zhejiang
N
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Article
(e) Kim, H.; Ho, S.; Leighton, J. L. A More Comprehensive and
Highly Practical Solution to Enantioselective Aldehyde Crotylation. J.
Am. Chem. Soc. 2011, 133, 6517−6520. (f) Lachance, H.; Lu, X.;
Gravel, M.; Hall, D. G. Scandium-Catalyzed Allylboration of
Aldehydes as a Practical Method for Highly Diastereo- and
Enantioselective Construction of Homoallylic Alcohols. J. Am.
Chem. Soc. 2003, 125, 10160−10161. (g) Loh, T. P.; Lin, M. J.;
Tan, K. L. Indium-mediated propargylation of aldehydes: regiose-
lectivity and enantioselectivity studies. Tetrahedron Lett. 2003, 44,
507−509. (h) Zhu, S. F.; Yang, Y.; Wang, L. X.; Liu, B.; Zhou, Q. L.
Synthesis and Application of Chiral Spiro Phospholane Ligand in Pd-
Catalyzed Asymmetric Allylation of Aldehydes with Allylic Alcohols.
Org. Lett. 2005, 7, 2333−2335.
Strategies in Intramolecular Allylation of Aldehydes with Allylsilanes.
J. Org. Chem. 2008, 73, 5462−5475.
(6) (a) Lee, J.; Torker, S.; Hoveyda, A. H. Versatile Homoallylic
Boronates by Chemo-, SN2’-, Diastereo- and Enantioselective
Catalytic Sequence of Cu-H Addition to Vinyl-B(pin)/Allylic
Substitution. Angew. Chem., Int. Ed. 2017, 56, 821−826. (b) van
der Mei, F. W.; Qin, C.; Morrison, R. J.; Hoveyda, A. H. Practical,
Broadly Applicable, α-Selective, Z-Selective, Diastereoselective, and
Enantioselective Addition of Allylboron Compounds to Mono-, Di-,
Tri-, and Polyfluoroalkyl Ketones. J. Am. Chem. Soc. 2017, 139, 9053−
9065. (c) Fager, D. C.; Lee, K.; Hoveyda, A. H. Catalytic
Enantioselective Addition of an Allyl Group to Ketones Containing
a Tri-, a Di-, or a Monohalomethyl Moiety. Stereochemical Control
Based on Distinctive Electronic and Steric Attributes of C-Cl, C-Br,
and C-F Bonds. J. Am. Chem. Soc. 2019, 141, 16125−16138.
(d) Morrison, R. J.; van der Mei, F. W.; Romiti, F.; Hoveyda, A. H. A
Catalytic Approach for Enantioselective Synthesis of Homoallylic
Alcohols Bearing a Z-Alkenyl Chloride or Trifluoromethyl Group. A
Concise and Protecting Group-Free Synthesis of Mycothiazole. J. Am.
Chem. Soc. 2020, 142, 436−447. (e) Robbins, D. W.; Lee, K.; Silverio,
D. L.; Volkov, A.; Torker, S.; Hoveyda, A. H. Practical and Broadly
Applicable Catalytic Enantioselective Additions of Allyl-B(pin)
Compounds to Ketones and a-Ketoesters. Angew. Chem., Int. Ed.
2016, 55, 9610−9614.
(4) (a) Herold, T.; Hoffmann, R. W. Enantioselektive Synthese von
Homoallylalkoholen uber chirale Allylboronsaure-ester. Angew. Chem.
̈
̈
1978, 90, 822−823. (b) Brown, H. C.; Bhat, K. S. Enantiomeric Z-
and E-crotyldiisopinocamphenylboranes. Synthesis in high optical
purity of all four possible stereoisomers of beta-methylhomoallyl
alcohols. J. Am. Chem. Soc. 1986, 108, 293−294. (c) Roush, W. R.;
Ando, K.; Powers, D. B.; Palkowitz, A. D.; Halterman, R. L.
Asymmetric synthesis using diisopropyl tartrate modified (E)- and
(Z)-crotylboronates: preparation of the chiral crotylboronates and
reactions with achiral aldehydes. J. Am. Chem. Soc. 1990, 112, 6339−
6348. (d) Corey, E. J.; Yu, C. M.; Lee, D. H. A practical and general
enantioselective synthesis of chiral propa-1,2-dienyl and propargyl
carbinols. J. Am. Chem. Soc. 1990, 112, 878−879. (e) Kim, H.; Ho, S.;
Leighton, J. L. A More Comprehensive and Highly Practical Solution
to Enantioselective Aldehyde Crotylation. J. Am. Chem. Soc. 2011,
133, 6517−6520. (f) Usanov, D. L.; Yamamoto, H. Asymmetric
Nozaki−Hiyama Propargylation of Aldehydes: Enhancement of
Enantioselectivity by Cobalt Co-Catalysis. Angew. Chem., Int. Ed.
(7) (a) Kim, S. W.; Zhang, W.; Krische, M. J. Catalytic
Enantioselective Carbonyl Allylation and Propargylation via Alco-
hol-Mediated Hydrogen Transfer: Merging the Chemistry of
Grignard and Sabatier. Acc. Chem. Res. 2017, 50, 2371−2380.
(b) Shin, I.; Krische, M. J. Asymmetric Iridium Catalyzed C-C
Coupling of Chiral Diols via Site-Selective Redox-Triggered Carbonyl
Addition. Site-Selective Catalysis; Topics in Current Chemistry;
Springer, 2015; Vol. 372, pp 85−101. (c) Dechert-Schmitt, A.-M.
R.; Schmitt, D. C.; Krische, M. J. Site-Selective Primary Alcohol
Dehydrogenation Enables Protecting Group-Free Diastereoselective
C-C Coupling of 1,3-Glycols and Allyl Acetate. Angew. Chem., Int. Ed.
2013, 52, 3195−3198. (d) Shin, I.; Wang, G.; Krische, M. J. Catalyst-
Directed Diastereo- and Site-Selectivity in Successive Nucleophilic
and Electrophilic Allylations of Chiral 1,3-Diols: Protecting Group-
Free Synthesis of 4-Hydroxy-2,6-cis- or trans-Pyrans. Chem. − Eur. J.
2014, 20, 13382−13389. (e) Zbieg, J. R.; Yamaguchi, E.; McInturff, E.
L.; Krische, M. J. Enantioselective C-H Crotylation of Primary
Alcohols via Hydrohydroxyalkylation of Butadiene. Science 2012, 336,
324−327. (f) Geary, L. M.; Woo, S. K.; Leung, J. C.; Krische, M. J.
Diastereoand Enantioselective Iridium Catalyzed Carbonyl Propargy-
lation from the Alcohol or Aldehyde Oxidation Level: 1,3-Enynes as
Allenylmetal Equivalents. Angew. Chem., Int. Ed. 2012, 51, 2972−
2976.
́
2010, 49, 8169−8172. (g) Althaus, M.; Mahmood, A.; Suarez, J. R.;
Thomas, S. P.; Aggarwal, V. K. Application of the Lithiation−
Borylation Reaction to the Preparation of Enantioenriched Allylic
Boron Reagents and Subsequent in Situ Conversion into 1,2,4-
Trisubstituted Homoallylic Alcohols with Complete Control over All
Elements of Stereochemistry. J. Am. Chem. Soc. 2010, 132, 5922.
(h) Hirayama, L. C.; Haddad, T. D.; Oliver, A. G.; Singaram, B.
Direct Synthesis of B-Allyl and B-Allenyldiisopinocampheylborane
Reagents Using Allyl or Propargyl Halides and Indium Metal Under
Barbier-Type Conditions. J. Org. Chem. 2012, 77, 4342−4353.
(i) Inoue, M.; Nakada, M. Studies on Catalytic Asymmetric
Nozaki−Hiyama Propargylation. Org. Lett. 2004, 6, 2977−2980.
(j) Kira, M.; Sato, K.; Sakurai, H. Chemistry of organosilicon
compounds. 240. Pentacoordinate allylsilicates: characterization and
highly stereoselective reaction with aldehydes. J. Am. Chem. Soc. 1988,
110, 4599−4602.
(5) For the selected examples of Lewis Acids catalyzed chiral
allylation with allylsilanes and allylstannanes (a) Denmark, S. E.;
Almstead, N. G. Stereochemical Studies on the Addition of
Allylsilanes to Aldehydes. The SE’ Component. J. Org. Chem. 1994,
59, 5130−5132. (b) Denmark, S. E.; Hosoi, S. Stereochemical Studies
on the Addition of Allylstannanes to Aldehydes. The SE’ Component.
J. Org. Chem. 1994, 59, 5133−5135. (c) Wolf, L. M.; Denmark, S. E.
A Theoretical Investigation on the Mechanism and Stereochemical
Course of the Addition of (E)-2-Butenyltrimethylsilane to Acetalde-
hyde by Electrophilic and Nucleophilic Activation. J. Am. Chem. Soc.
2013, 135, 4743−4756. (d) Bode, J. W.; Gauthier, D. R., Jr.; Carreira,
E. M. Facile enantioselective synthesis of a key homoallylic alcohol
building block for polyketide synthesis: TiF4-BINOL catalyzed
allylsilylation with allyl trimethylsilane. Chem. Commun. 2001, 24,
2560−2561. (e) Keck, G. E.; Savin, K. A.; Cressman, E. N. K.; Abbott,
D. E. Effects of Olefin Geometry on the Stereochemistry of Lewis
Acid Mediated Additions of Crotylstannanes to Aldehydes. J. Org.
Chem. 1994, 59, 7889−7896. (f) Keck, G. E.; Dougherty, S. M.; Savin,
K. A. Intramolecular Allylstannane-Aldehyde Cyclizations: Stereo-
chemical Results with Flexible Tethers for Reactions Forming
Vinylcyclohexanols. J. Am. Chem. Soc. 1995, 117, 6210−6223.
(g) Beignet, J.; Jervis, P. J.; Cox, L. R. Temporary Silicon Connection
(8) Both enantiomers of TRIP-PA (R and S) are commercially
available or prepared from BINOL using a literature procedure see
Hoffmann, S.; Seayad, A.; List, B. A Powerful Brønsted Acid Catalyst
for the Organocatalytic Asymmetric Transfer Hydrogenation of
Imines. Angew. Chem., Int. Ed. 2005, 44, 7424−7427.
(9) Jain, P.; Antilla, J. C. Chiral Brønsted Acid-Catalyzed
Allylborations of Aldehydes. J. Am. Chem. Soc. 2010, 132, 11884−
11886.
(10) (a) Hemelaere, R.; Carreaux, F.; Carboni, B. A Diastereose-
lective Route to trans-2-Aryl-2,3-dihydrobenzofurans through Se-
quential Cross-Metathesis/Isomerization/Allylboration Reactions:
Synthesis of Bioactive Neolignans. Eur. J. Org. Chem. 2015, 2015,
2470−2481. (b) Itagaki, T.; Kawamata, A.; Takeuchi, M.; Hamada,
K.; Iwabuchi, Y.; Eguchi, T.; Kudo, F.; Usui, T.; Kanoh, N. Synthesis
and structure−activity relationship study of FD-891: importance of
the side chain and C8−C9 epoxide for cytotoxic activity against
cancer cells. J. Antibiot. 2016, 69, 287−293. (c) Feng, J.; Lei, X.; Bao,
R.; Li, Y.; Xiao, C.; Hu, L.; Tang, Y. Enantioselective and Collective
Total Syntheses of Xanthanolides. Angew. Chem., Int. Ed. 2017, 56,
16323−16327. (d) Wu, J.; Lorenzo, P.; Zhong, S.; Ali, M.; Butts, C.
P.; Myers, E. L.; Aggarwal, V. K. Synergy of synthesis, computation
O
https://dx.doi.org/10.1021/acs.joc.0c01646
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
and NMR reveals correct baulamycin structures. Nature 2017, 547,
436−440.
from Terminal Alkynes. Angew. Chem., Int. Ed. 2019, 58, 14620−
14624.
(11) (a) Jain, P.; Wang, H.; Houk, K. N.; Antilla, J. C. Brønsted Acid
Catalyzed Asymmetric Propargylation of Aldehydes. Angew. Chem.,
Int. Ed. 2012, 51, 1391−1394. (b) Reddy, L. R. Chiral Brønsted Acid
Catalyzed Enantioselective Propargylation of Aldehydes with
Allenylboronate. Org. Lett. 2012, 14, 1142−1145. Identical ee value
was obtained as Reddy’s report under similar comditions (c) Chen,
M.; Roush, W. R. Enantioselective Synthesis of anti- and syn-
Homopropargyl Alcohols via Chiral Brønsted Acid Catalyzed
Asymmetric Allenylboration Reactions. J. Am. Chem. Soc. 2012, 134,
10947−10952. (d) Incerti-Pradillos, C. A.; Kabeshov, M. A.; Malkov,
A. V. Highly Stereoselective Synthesis of Z-Homoallylic Alcohols by
Kinetic Resolution of Racemic Secondary Allyl Boronates. Angew.
Chem., Int. Ed. 2013, 52, 5338−5341. (e) Huang, Y.; Yang, X.; Lv, Z.;
Cai, C.; Kai, C.; Pei, Y.; Feng, Y. Asymmetric Synthesis of 1,3-
Butadienyl-2-carbinols by the Homoallenylboration of Aldehydes with
a Chiral Phosphoric Acid Catalyst. Angew. Chem., Int. Ed. 2015, 54,
7299−7302. (f) Rodríguez, E.; Grayson, M. N.; Asensio, A.; Barrio,
P.; Houk, K. N.; Fustero, S. Chiral Brønsted Acid-Catalyzed
Asymmetric Allyl(propargyl)boration Reaction of ortho-Alkynyl
Benzaldehydes: Synthetic Applications and Factors Governing the
Enantioselectivity. ACS Catal. 2016, 6, 2506−2514. (g) Yang, X.;
Pang, S.; Cheng, F.; Zhang, Y.; Lin, Y. W.; Yuan, Q.; Zhang, F. L.;
Huang, Y. Y. Enantioselective Synthesis of 1,3-Disubstituted 1,3-
Dihydroisobenzofurans via a Cascade Allylboration/Oxo-Michael
Reaction of o-Formyl Chalcones Catalyzed by a Chiral Phosphoric
Acid. J. Org. Chem. 2017, 82, 10388−10397. (h) Hetzler, B. E.;
Volpin, G.; Vignoni, E.; Petrovic, A. G.; Proni, G.; Hu, C. T.; Trauner,
D. A Versatile Bis-Allylboron Reagent for the Stereoselective
Synthesis of Chiral Diols. Angew. Chem., Int. Ed. 2018, 57, 14276−
14280. (i) Xing, C. H.; Liao, Y. X.; Zhang, Y.; Sabarova, D.; Bassous,
M.; Hu, Q. S. Asymmetric Allylboration of Aldehydes with Pinacol
Allylboronates Catalyzed by 1,1-Spirobiindane-7,7-diol (SPINOL)
Based Phosphoric Acids. Eur. J. Org. Chem. 2012, 1115−1118.
(j) Gao, S.; Duan, M.; Houk, K. N.; Chen, M. Chiral Phosphoric Acid
Dual-Function Catalysis: Asymmetric Allylation with α-Vinyl
Allylboron Reagents. Angew. Chem., Int. Ed. 2020, 59, 10540−
10548. (k) Pankaj, J. Brønsted Acid Catalyzed Asymmetric Allylation
and Propargylation of Aldehydes. Ph.D. Thesis, University of South
Florida, 2014.
(13) For computational aspects of chiral-BINOL phosphoric acid-
catalyzed allylboration and propargylations, see (a) Grayson, M. N.;
Pellegrinet, S. C.; Goodman, J. M. Mechanistic Insights into the
BINOL-Derived Phosphoric Acid-Catalyzed Asymmetric Allylbora-
tion of Aldehydes. J. Am. Chem. Soc. 2012, 134, 2716−2722.
(b) Wang, H.; Jain, P.; Antilla, J. C.; Houk, K. N. Origins of
Stereoselectivities in Chiral Phosphoric Acid Catalyzed Allylborations
and Propargylations of Aldehydes. J. Org. Chem. 2013, 78, 1208−
1215. (c) Grayson, M. N.; Goodman, J. M. Understanding the
Mechanism of the Asymmetric Propargylation of Aldehydes
Promoted by 1,1′-Bi-2-naphthol-Derived Catalysts. J. Am. Chem.
Soc. 2013, 135, 6142−6148.
(14) CCDC 1960914 contains the supporting crystallographic data
for this paper (substrate 30). These data can be obtained free of
charge from the Cambridge Crystallographic Data Centre via https://
www.ccdc.cam.ac.uk/.
(15) (a) Tian, Y.; Ding, Y.; Xu, X.; Bai, Y.; Tang, Y.; Hao, X.; Zhang,
W.; Chen, Y. Total synthesis and biological evaluation of nannocystin
analogues modified at the polyketide phenyl moiety. Tetrahedron Lett
2018, 59, 3206−3209. (b) Huang, J.; Wang, Z. Total Syntheses of
Nannocystins A and A0, Two Elongation Factor 1 Inhibitors. Org.
Lett. 2016, 18, 4702−4705.
(16) Barnett, D. S.; Moquist, P. N.; Schaus, S. E. The Mechanism
and an Improved Asymmetric Allylboration of Ketones Catalyzed by
Chiral Biphenols. Angew. Chem., Int. Ed. 2009, 48, 8679−8682.
(17) Zhang, P.; Roundtree, I. A.; Morken, J. P. Ni- and Pd-Catalyzed
Synthesis of Substituted and Functionalized Allylic Boronates. Org.
Lett. 2012, 14, 1416−1419.
(18) Pei, W.; Krauss, I. J. Homoallylboration and Homocrotylbora-
tion of Aldehydes. J. Am. Chem. Soc. 2011, 133, 18514−18517.
(19) Wadamoto, M.; Ozasa, N.; Yanagigawa, A.; Yamamoto, H.
BINAP/AgOTf/KF/18-Crown-6 as New Bifunctional Catalysts for
Asymmetric Sakurai−Hosomi Allylation and Mukaiyama Aldol
Reaction. J. Org. Chem. 2003, 68, 5593−5601.
(20) Wu, T. R.; Shen, L.; Chong, M. Asymmetric Allylboration of
Aldehydes and Ketones Using 3,3‘-Disubstituted binaphthol-Modified
Boronates. Org. Lett. 2004, 6, 2701−2704.
(21) Rauniyar, V.; Zhai, H.; Hall, D. G. Catalytic Enantioselective
Allyl- and Crotylboration of Aldehydes Using Chiral Diol.SnCl4
Complexes. Optimization, Substrate Scope, and Mechanism Inves-
tigations. J. Am. Chem. Soc. 2008, 130, 8481−8490.
(22) Lee, J.; Miller, J. J.; Hamilton, S. S.; Sigman, S. S.
Stereochemical Diversity in Chiral Ligand Design: Discovery and
Optimization of Catalysts for the Enantioselective Addition of Allylic
Halides to Aldehydes. Org. Lett. 2005, 7, 1837−1839.
(23) Iseki, K.; Mizuno, S.; Kuroki, Y.; Kobayashi, Y. Asymmetric
Allylation with Chiral Formamide Catalysts. Tetrahedron 1999, 55,
977−988.
(24) Denmark, S. E.; Fu, J.; Lawler, M. J. Chiral Phosphoramide-
Catalyzed Enantioselective Addition of Allylic Trichlorosilanes to
Aldehydes. Preparative Studies with Bidentate Phosphorus-Based
Amides. J. Org. Chem. 2006, 71, 1523−1536.
(25) Denmark, S. E.; Wynn, T. Lewis Base Activation of Lewis
Acids: Asymmetric Allylations of Aromatic Aldehydes. J. Am. Chem.
Soc. 2001, 123, 6199−6200.
(26) Trost, B. M.; Ngai, M. Y.; Dong, G. Ligand-accelerated
Enantioselective Propargylation of Aldehydes via Allenylzinc
Reagents. Org. Lett. 2011, 13, 1900−1903.
́
́
(12) (a) Fustero, S.; Rodríguez, E.; Lazaro, R.; Herrera, L.; Catalan,
S.; Barrio, P. Relay Catalysis: Enantioselective Synthesis of Cyclic
Benzo-Fused Homoallylic Alcohols by Chiral Brønsted Acid-
Catalyzed Allylboration/Ring Closing Metathesis. Adv. Synth. Catal.
2013, 355, 1058−1064. (b) Miura, T.; Nishida, Y.; Morimoto, M.;
Murakami, M. Enantioselective Synthesis of Anti Homoallylic
Alcohols from Terminal Alkynes and Aldehydes Based on
Concomitant Use of a Cationic Iridium Complex and a Chiral
Phosphoric Acid. J. Am. Chem. Soc. 2013, 135, 11497−11500.
(c) Calder, E. D. D.; Sutherland, A. Enantioselective Synthesis of 3-
Methyleneindan-1-ols via a One-Pot Allylboration−Heck Reaction of
2-Bromobenzaldehydes. Org. Lett. 2015, 17, 2514−2517. (d) Tao, Z.
L.; Li, X. H.; Han, Z. Y.; Gong, L. Z. Diastereoselective Carbonyl
Allylation with Simple Olefins Enabled by Palladium Complex-
Catalyzed C−H Oxidative Borylation. J. Am. Chem. Soc. 2015, 137,
4054−4057. (e) Miura, T.; Nakahashi, J.; Murakami, M. Enantiose-
lective Synthesis of (E)-δ-Boryl-Substituted anti-Homoallylic Alcohols
Using Palladium and a Chiral Phosphoric Acid. Angew. Chem., Int. Ed.
2017, 56, 6989−6993. (f) Miura, T.; Nakahashi, J.; Zhou, W.;
Shiratori, Y.; Stewart, S. G.; Murakami, M. Enantioselective Synthesis
of anti-1,2-Oxaborinan-3-enes from Aldehydes and 1,1-Di(boryl)alk-
3-enes Using Ruthenium and Chiral Phosphoric Acid Catalysts. J. Am.
Chem. Soc. 2017, 139, 10903−10908. (g) Li, L. L.; Su, Y. L.; Han, Z.
Y.; Gong, L. Z. Assembly of Tetrahydropyran Derivatives from
Aldehydes, Allylboronates, and Syngas by Asymmetric Relay Catalytic
Cascade Reaction. Chem. − Eur. J. 2018, 24, 7626−7630. (h) Miura,
T.; Oku, N.; Murakami, M. Diastereo- and Enantioselective Synthesis
of (E)-δ-Boryl-Substituted anti-Homoallylic Alcohols in Two Steps
(27) Ramachandran, P. V.; Prabhudas, B.; Chandra, J. S.; Reddy, M.
V. Diastereoselective Dihydroxylation and RegioselectiveDeoxygena-
tion of Dihydropyranones: A Novel Protocol for the Stereoselective
Synthesis of C1-C8 and C15-C21Subunits of(+)-Discodermolide. J.
Org. Chem. 2004, 69, 6294−6304.
P
https://dx.doi.org/10.1021/acs.joc.0c01646
J. Org. Chem. XXXX, XXX, XXX−XXX