Syntheses of Chiral Lactones via Asymmetric Allylboration - American

Chapter 16

Syntheses of Chiral Lactones via Asymmetric Allylboration

Downloaded by NORTH CAROLINA STATE UNIV on December 11, 2012 | http://pubs.acs.org Publication Date: February 26, 2001 | doi: 10.1021/bk-2001-0783.ch016

M. V e n k a t Ram R e d d y , H e r b e r t C. B r o w n , a n d P. V e e r a r a g h a v a n R a m a c h a n d r a n *

Herbert C. Brown Center for Borane Research, Purdue University, West Lafayette, IN 47907-1393

The syntheses of lactenones and lactones of different ring sizes in high enantiomeric excesses involving asymmetric allylboration with B-allyldiisopinocampheylborane have been described (1). γ-Substituted γ-butyrolactones have been synthesized from homoallyl alcohols via a protection -hydroboration-oxidation-deprotection-cyclization sequence. The unique nature of α-perfluoroalkyl homoallyl alcohols has been exploited for the synthesis of γ-perfluoroalkyl γ -butyrolactones without protecting the alcohols. Allylboration of formyl esters provide a general route to prepare ω-allyl and ω-propyllactones. The ring-closing metathesis of homoallyl enoates provides a methodology to prepare a variety of αpyranone-containing natural products.

Introduction Lactones are important synthons in organic chemistry (2). Scheme 1 represents some of the transformations that can be achieved via lactones. They

220

© 2001 A m e r i c a n C h e m i c a l Society

In Organoboranes for Syntheses; Ramachandran, P., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2001.

221

are also present in a large number of natural products (3). Accordingly, the synthesis of lactones has attracted the attention of organic chemists. Until recently, the most commonly used methodology for the preparation of chiral lactones was asymmetric reduction of keto esters (4) or enzymatic esterification of hydroxy esters (J), followed by cyclization.

(i) L D A , (ii) PhSeBr


(i) Dibal-H .

R

Ο

(ii) MsCl, E t N

(iii) H 0 2

3

2

Ο ^V'N?

0) L D A , TMSC1 (ii) PhSCH X, ZnBr 2

(i) L D A , (ii) R X 2

(iii) N a I 0 A 4i

Scheme 1, Applications of lactones in organic syntheses

Recently we undertook the preparation of chiral lactones of different ring sizes utilizing chiral homoallylic alchols derived from the asymmetric allylboration of appropriate aldehydes as the starting materials (6-5). Our procedures are reviewed here. The application of our allylborationesterification-ring closing metathesis reaction sequence for the synthesis of biologically active natural products (8Ί1) are also summarized.

Asymmetric Allylboration Asymmetric allyl- and crotylboration and related reactions of aldehydes provide an excellent route for the synthesis of various types of homoallylic alcohols. During the course of our research involving pinane-based versatile reagents (PVR) for asymmetric syntheses (72), we have developed various allylborating agents (1-8, 11) (13-20). Several others also have contributed to the development of asymmetric allylborating agents (9-10) using oc-pinene as the chiral auxiliary (Figure 1) (21-22).



222

1: Χ, Υ, Ζ = H 2: Χ, Ζ = Η, Y = Me 3: Χ, Y = Η, Ζ = Me 4: Χ = Me, Υ, Ζ = Η 5: Χ = Η, Υ, Ζ = Me

6: Χ = vinyl, Υ, Ζ = Η 7: X , Z

= H,Y

=

OMe

8: Χ, Y = H,Z

= B(OR)

9: X , Y

= NPh

10:

Figure 1. Pinane-based

= H,Z

2

2

Χ, Y = Η, Ζ = Cl

versatile

reagents for

allylboration

Many other allylborating agents (12-21) utilizing chiral auxiliaries derived from carenes, camphor, tartaric acid, stein, etc. are also known (Figure 2) (2333). Recently Villieras described an ester-containing chiral allylborating agent which could be used directly for the synthesis of a-methylene-y-butyrolactones (32). In this review, we have restricted our discussions to the synthesis of lactones via homoallylic alcohols derived from β-allyldiisopinocampheylborane, 1.

S0 Tol 2

Ph EtO Ph

Ε Ι 0

17 Bn

S0 Tol 2

Ο

14:X

=OZ

15:X

= NS0 Me,Z = H

16:X

= 0 , Z = COOEt

t

= H 2

ΝΛΟ'

I

18

2 0 : R i = R = Me 2

21:Ri = H, R = SiMe 2

/ Ν "Λ\ Bri

19

Ο

Figure 2. Reagents for asymmetric

allylboration


3

223


Allylboration with B-AUyldiisopinocampheylborane. Since the introduction of this reagent in 1983 (12), it has been utilized in key steps in several syntheses. The reagent can be prepared by the treatment of allyl Grignard reagent with either B-chlorodiisopinocampheylborane (DIPChloride™) (34, 35) or B-methoxydiisopinocampheylborane (72). A variety of aldehydes, including perfluoroalkyl (36) and heterocyclic aldehydes (37) have been tested with this reagent to demonstrate its capability. In all of the cases examined thus far the product homoallyl alcohols were obtained in >92% ee (Scheme 2). It has been established that in the case of chiral aldehydes, the reagent controls the diastereoselectivity (38). H

)

1

MgBr^A^-- ) B

B C 1

2

RCHO

2

E t 0 , -78 °C R = Me, Ph, C F , etc. 2

3

(-)-DIP-Chloride™ % Η

OBIpc R

A^^

2

99%ee

Scheme 2. Preparation and reactions of B-allyldiisopinocampheylborane

y-Substituted-y-lactones Our first synthesis of lactones via allylboration involved the protection of homoallylic alcohols as a p-nitrobenzoate ester, followed by hydroboration with chloroborane and oxidation of the intermediate with C r 0 in acetic acid. Deprotection under basic conditions provided the lactones in very high yields with the same enantiomeric excesses as the starting homoallyl alcohols (Scheme 3) (6). 3

Fluorinated Lactones Due to the importance of fluorinated organic molecules in agro-, bio-, materials, and medicinal chemistry we subjected a series of fluorinated


224 Ο

Λ

R

OH

Η

R l . B H O S M e , CH C1 2

2

2

R

Q //

h


^

98-99% ee = Me, i-Pr, r-Bu, Ph, etc.

2

PNBO

rti2

A

CO2H1.NaOH.8O-C.lh

2. Cr0 , AcOH/H 0 rt, ih 3

ΟΡΝΒ

r

ν

R' t

p-NO PhCOCl

2. cone. HC1

2

Q

R' 98-99% ee

Scheme 3. Synthesis of γ-substituted fbutyrolactones

aldehydes to the allylboration-lactonization reaction sequence. Initially, we applied the same sequence in Scheme 3 to prepare y-perfluoroalkyl(aryl) γlactones. Later we modified our synthesis. The inertness of perfluorinated 2°alcohols to Cr(VI) oxidation (39) allowed elimination of the protectiondeprotection sequence. Thus, hydroboration of the homoallyl alcohols with two equiv of dichloroborane provided the corresponding intermediate, which upon Jones oxidation in the same pot afforded the lactones in 60-70% yields (Scheme 4). This one-pot procedure is not applicable to non-fluorinated alcohols.

1

Ο Rc

-100 ° c Η

_ Et 0-pentane 12

v

HBCI (2 eq.) 2

OH [ 0 ] >

Rc ^ 95-> 99% ee n

c

Jones oxidation

n

f

W

Ο

95-> 99% ee Scheme 4, Synthesis of γ-fluoroalkyl fbutyroiactones


225 coAUyl- and oPropyllaetones.


Asymmetric allylboration of aldehydes containing an adjacent ester group with #-allyldiisopinocampheylborane, followed by hydrolysis and cyclization, provides the corresponding ω-allyllactones in high yields and > 92% enantiomeric excess. Hydrogénation of these lactones provides the corresponding w-propyllactones without any loss of optical purity (Scheme 5) (7).

OH COOMe η = 0-4

l î E t

2°

OH H

XOOMe

-100 °C, 1 h 92-99% ee p-TsOH, Δ

2

/ N i

XOOMe

p-TsOH, Δ

ο

Syntheses of Chiral Lactones via Asymmetric Allylboration - American

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