J. Org. C h e m . 1991,56,4913-4918 over magnesium sulfate, filtered, and concentrated in vacuo to give 120 mg of crude 30 and benzyloxezolidinone. Flash chromatography (&l hexaneEt0Ac) gave 52 mg (95%) of pure 3 0 'H NMR (CDC13) 6 7.29-7.39 (m, 5), 5.10 (8, 2, CHzPh), 4.92 (8, 1,-CHH), 4.74 (8, 1, -CHH), 2.34 (t,2, J = 7.7, CHZCO), 2.25 (m, 1, CHCHS), 1.75 (ddt, 1,J = 7.3,13.7,7.6, CHHCH), 1.74 (ddt, 1,J = 7.4, 13.7,7.6, CHHCH), 1.04 (d, 3, J = 6.8),1.02 (s,9); 'Bc NMR (CDClS) 6 173.7,163.1,136.1,128.5,128.3,128.2,105.2,66.1, 36.6,33.4 (2 C), 32.7, 28.8, 23.6; IR (neat) 1740 cm-';["ID -16.6O (C 0.247, CHCl3). Benzyl S-Oxo-4,6,6-trimethylheptanoate (31).aa A solution of 40 mg (0.14 mmol) of 30 in 3 mL of CHzClz was cooled to -78 "C, and O3 was passed through the solution for 1 min. The reaction was quenched by 1.4 equiv of dimethyl sulfide, and the solution was stirred at 25 OC for 30 min. The solution was diluted with 2 mL of water and extracted twice with CH2C12. The combined organic layera were washed with brine, dried (MgSOJ, and concentrated in vacuo to give 42 mg of crude 31. Flash chrohexane-EtOAc) gave 34 mg (85%)of pure 31: matography (a1 'H NMR (CDC13)6 7.30-7.39 (m, 5), 5.11 (a,2, CHzPh), 3.05 (br sext, 1, J = 7.0, CHCHS),2.30 (t, 1,J = 7.5, CHHCO), 2.29 (t, 1,J = 7.3, CHHCO), 1.94 (dddd, 1,J = 7.3,7.5,7.1,14.0, CHHCH), 1.68 (dddd, 1, J = 7.3, 7.5, 7.1, 14.0, CHHCH), 1.10 (8, 9), 1.04 (d, 3, J = 6.8); '% N M R (CDClS) 6 173.0,135.8,128.5,128.3,128.2, 66.2,44.6, 38.4, 31.8,28.8, 26.0, 18.2; IR (neat) 1740, 1705 cm-';, [a]D-18.8O (c 0.268, CHCl,); [e] +397O at 285 nm. (S)-sec-Butyl tert-Butyl Ketone (32). t-BuLi (2.0 equiv) was added dropwise during 20 min to a solution of (S)-(+)-2methylbutyric acid (0.5 mL, 4.5 mmol, 98% pure) in 10 mL of anhydrous ether at 0 OC. The mixture was stirred overnight, and the reaction mixture was hydrolyzed by pouring it slowly into 15
4913
mL of water. The organic phaw was separated, and the aqueous layer was extracted twice with 15 mL of ether. The combined organic layers were washed with brine, dried (MgSO,), and concentrated in vacuo to give 0.6 g of crude 32 as a clear yellow liquid. Distillation of the crude product at 20 Torr gave 0.35 g (45%) of ketone 32, bp 60-65 OC: 'H NMR 6 2.91 (br sext, 1,J = 7-01, 1.62 (m, l), 1.33 (m, I),1.15 (a, 9), 1.03 (d, 3, J = 6.7), 0.84 (t, 3, J = 7.4); [ab +27.7O (c 0.132, CHCl,); [a]D -29.6O for the R enantiomer, [e] +280° at 308 nm. Re&tw NO.lb, 90719-30-5; 4,109299-92-5; 5,134178-33-9; 6, 134178-34-0; 7, 134178-35-1;9, 134178-36-2; 10, 134178-37-3; 12, 134178-38-4;13, 134178-39-5;14 (isomer l),134178-40-8; 14 (isomer 2), 134178-41-9; 15, 134178-42-0; 16, 134178-43-1; 18, 134178-44-2; 19,134178-45-3;20,134178-46-4; 21,2043-21-2; 22, 134178-47-5;23, 134178-48-6; 24, 134178-49-7; 25, 134178-50-0; 26,90719-27-0;27a, 134178-51-1; 27b, 13417852-2;28,13417853-3; 29,134178-54-4;30,134178-55-5; 31,134178-56-6; 32,134178-57-7; MezAICl, 1184-58-3; methylenecyclopentane, 1528-30-9; isobutylene, 11511-7; 2-ethyl-1-butene, 760-21-4; allyltrimethylsilane, 762-72-1; ethylidenecyclohexane, 1003-64-1; (E)-3,4,4-trimethyl-2-pentene,39761-57-4; 1-methylcycloheptene,1453-254; (S)-(+)-2-methylbutyric acid, 1730-91-2. Supplementary Material Available: Experimental details for the ene reactions of the achiral oxazolidinones 4 and 21 (3 pages). Ordering information is given on any current masthead Page. (27) Brown, H.C.; Srebnik, M.; Bakshi, R. K.; Cole, T. E. J. Am. Chem. SOC.1987,109,5420.
Synthesis of Enantioenriched a-Hydroxy-a-allenylaceticAcids by [2,3] Wittig Rearrangement of a-(Propargy1oxy)acetates James A. Marshall* and Xiao-jun Wang Department of Chemistry, The University of South Carolina, Columbia, South Carolina 29208 Received February 22,1991
Optically active (R)-(propargy1oxy)acetic esters 5, available in ca. 90% ee through reduction of alkynones 2 with Chirald-LiAlH4 followed by alkylation with chloroacetic acid and esterification with CHSNZ, undergo highly stereoselective [2,3] rearrangement upon treatment with LDA in THF at -78 OC followed by CpzZrC19to afford a(s)-hydroxy-B(R)-alleniceetsrs 7 with complete transfer of chirality and >90% diaatereoeelectivity. Upon treatment with TESOTf in EhN the (R)-(propargy1oxy)aceticesters 5 afford the diastereomeric a-(R)-hydroxy-/3-(R)-allenic esters 8 stereoselectively. Both hydroxy esters 7 and 8 cyclize stereospecifically to trans- and cis-2,5dihydrofurans 13-15 and 17-19 upon treatment with AgNOS-CaC03, PhSeCl, or NBS.
We recently showed that enantioenriched a-hydroxy-aallenylacetic acids I1 can be readily prepared by [2,3] Wittig rearrangement of chiral a-(propargy1oxy)acetates (eq l).' The reaction proceeds with excellent diastereo-
I
ds-91 .looO/o ~
(s)
0
~
~
OH
3
E+
R'
3
0
R' R3O2C.~,\ H
@?o(RR2
(1 1
111 R4 = H, Br, SePh
II
selectivity, especially when CppZrClpis added to chelate (1) Manhall, J. A,; Robinnon, E. 64, 5854.
D.;Zapata, A. J. Org.Chem. 1989,
the ether and carboxylic groupings.2 Cyclization of the allenyl alcohol produds II is readily effected with AgNOS, NBS,or PhSeCl to give the tri- or tetrasubstituted 2,5dihydrofurans I11 stereospecifi~ally.~Such furans are of interest as subunits of various natural products.' Propargylic [2,3] rearrangements differ from their allylic counterparts in that the chiral sense of the sp3 carbinyl center is faithfully transferred to the deny1 moiety of the product as a consequence of a rigid five-center transition state (A in Figure 1J1 In contrast, the stereogenicity of analogous allylic ether rearrangements, though generally high, depends upon conformational, and to some extent, (2) CE Kuroda, S.; Sakaguchi, S.; Ikegami, S.; Harramoto,T.;Kabuki, T.; Yamaguchi, M. Tetrahedron Lett. 1988, 29, 4763. Uckkawa, M.; Kabuki, T.; Yamaguchi, M. Tetrahedron Lett. 1986,27, 4681. (3) For a preliminary account, see: Marahall, J. A,; Wmg, X.-j. J. Org. Chem. 1990,56,2996. (4) Cf: Boivin, T. L. B. Tetrahedron 1987,43,3309. Mulhobd, R. L., Jr.; Chamberlin, A. R. J. Org. Chem. 1988, 63, 1082. Perron, F.; Albizati, K. F. Chem. Reu. 1989,89,1617.
0022-326319111956-4913$02.50/0 0 1991 American Chemical Society
Marshall and Wang
4914 J. Org. Chem., Vol. 56, No. 16, 1991 Scheme I
1. BuLi; R W
R1-a-t
Chirald
0
___c
IC R'=TMS
1. LDA, THF 2. C H 2 k (Tw1)
1
LDA, THF, Cp2ZrCI2
( T a b l y
G .
I.
RsSiOTf (Table 1)
Table I. [2,3]Wittig Rearrangements of (Propargy1oxy)aceticAcid Derivatives ..
IV
A H
V n
GO H, 5 P=Me
entry 1 2
Vlll
Figure 1. Comparative transition-state geometries for [2,3]rearrangements of propargylic and allylic ethers.
electronic preferences in envelope-like transition states (B Figure l)? Prior to our work only a few examples of propargylic ether rearrangements were kn0wn.B Hence, it was of interest to examine additional systems and conditions in order to define the scope of this potentially valuable synthetic methodology. The propargylic ethers 4 and 5 employed in these studies were prepared as outlined in Scheme I. Reduction of the acetylenic ketones 2 with Chirald7-LiA1H4 gave (R)propargylic alcohols 3 of 80->90% ee according to lH v8 C in
(5)N M ,T.; Mikami, K. Chem. Rev. 1986,86,885.Wu, Y-D., Houk, K.N.; Marshall, J. A. J. Org. Chem. lssO,bb, 1421. (6)Huche, M.; Cresson, P. Tetrahedron Lett. 1976,367. C a m , B.; Julia,S. Synth. Commun. 1977,7,273.Schollkopf,V.; Fellenberger, K.; Rizk, M.Liebiga Ann. Chem. 1970,734,108. (7) Aldrich Chemical Co. Chirald is a trade name for Darvon alcohol. Cf.: Yamaguchi, S.; Moeher, H.S . J. Org. Chem. 1973,38,1870.
ether
R1 R2 R3 conditions yield 7:8 A 80 937 C7H15 A 486 91:9 CHS B 1m0 57 3 5aa C7HI6 B 4 45' 1m0 Sbb CHS B od 5 Sdb H C 93 23:77 6 Saa C,Hlb 7 90 3268 C Sbb CHS C 8 Sdb H 91 2080 71 28:72 C 9 Scb TMS D 1090 10 96 C7H15 11 Sbb CHS D 1090 94 12 D 90 1090 488 C7H15 E a' 1090 Saa C7Hl5 13 Key: A = LDA, THF -78 "C; CH,N,; B = LDA, THF, -78 OC, CpzZrCl2;C = TMSOTf, EhN, CHiC1,; D = TESOTf, EhN, CH,Cl,; E = TBSOTf, EhN, CHzClp 46% elimination. '5% elimination. dTotal decomposition of starting material. (88% starting material after 12 h. 488 4bb
NMR analysis of the 0-methyl mandelate derivatives! It is worth noting that reduction of acetylenic ketone 2db by this methodology gave alcohol 3db of only 40% ee. The functionally equivalent TMS acetylenic ketone 2cb, on the (8)Trost, B. M.; Belletire, J. L.; Godleeki, S.; McDou al, P. D.; Balkovic, J. M.; Baldwin, J. J.; Chriety, M. E.; Ponticello, G. Varga, S. L.; Springer, J. D. J. Org. Chem. 1986,6I,2370. Dale, J. A.; Mollher, H. S. J. Am. Chem. SOC.1973,95,512.
l.;
J. Org. Chem., Vol. 56, No. 16, 1991 4915
Enantioenriched a-Hydroxy-a-AllenylaceticAcids other hand, yielded alcohol 3cb of >80% ee. Williamson etherification with chloroacetic acid afforded the ethers 4 in nearly quantitative yield. Treatment of the (propargy1oxy)acetic acids 4aa and 4bb with 2.5 equiv of LDA in THF at -78 "C for several hours followed by esterification with CH2N2led to the allenic hydroxy esters 7aa and 7bb in moderate to high yield (Table I, entries 1 and 2). GC analysis indicated a 937 mixture of stereoisomers in the former case and a 91:9 mixture in the latter. The configuration of the allene follows from the concerted nature of the [2,3]rearrangement (Figure 1).li6 The carbinyl configuration was established from chemical shift differences of the carbomethoxy protons in the 'H NMR spectrum of the 0methyl mandelate derivs. 9 and
a Figure 2. Transition states for [2,3]rearrangementa of (propargy1oxy)acetates leading to diastereomericallenols 7 and 8 (R' = ZrCp2C1 or SiR& Scheme I1
9
10
The yield of [2,3]rearrangement product 7bb was low because of a competing elimination reaction leading to the enyne 6 (1:l mixture of E and 2 isomers). Evidently, deprotonation of the acetylenic CH3 grouping is competitive with enolate formation. A related elimination product was not observed from ether 4aa. In an effort to minimize this elimination reaction and improve diastereoselectivity, we examined [2,3] rearrangement of the ester derivatives 5. Allyloxy analogues of ester 5 have been found to undergo highly stereoselective rearrangement upon conversion to their zirconium enoTreatment of ether ester Saa with LDA at -78 OC followed by Cp2ZrC12led to the rearranged allenic alcohol 7aa as the sole isolable product in 57% yield (Table I, entry 3). Analogous treatment of 5bb afforded allenic alcohol 7bb (45%) along with a small amount ( 5 % ) of elimination product 6 (Table I, entry 4). [2,3]Rearrangements of acids 4 or their esters 5 could also be effected with TMSOTf and Et3N along the lines reported by Mikami et al. for (allyloxy)acetates? Interestingly, the major diastereomer produced in these reactions was different from that of the base-promoted rearrangements (Table I, entries 6-9). Diastereoselectivity could be increased to 90:lO by use of TESOTf (Table I, entries 10-12). Use of the bulkier silylating agent, TBSOTf, led to no further improvement in diastereoselectivity and had the disadvantage of slow reaction rates (Table I, entry 13). The use of TESOTf to effect [2,3]rearrangement in these systems offere several advantages over the basepromoted reactions. Thus, elimination products such as 6 are not produced in the Si reactions. Furthermore, terminal alkynes can be employed (Table I, entry 8). Such alkynes decompose upon treatment with strong base (Table I, entry 5). The stereochemistry of allenols 8 was established through analysis of the 'H NMR spectra of the 0-methyl mandelate8 and on mechanistic grounds as noted for allenols 7.8 Conversion of 7 to 8 could be effected by Mitsunobu inversion with benzoic acid followed by methanolysis.1° The stereochemical trends in the foregoing rearrangements can be understood from transition-state consider(9) Mikruni, K.; T h h m h i , 0.;Tabei, T.; NaLai, T. Tetrahedron Lett.
.
1986.27.4611. ... -. , - - - -.
(10) Mitaunobu, 0. Synthesis 1981, 1.
R1-ap-H ..
1 a RI = C7H15 l b R'=CH3
1. BuLi, THF; BnOCHflHO D
2. PCC
0
Chirald
R1-E&
___)
\OBn 2ac RI = C7H15 2bc R1 = CH3
LiAIH4
..
2. CH2N2
3ac R' = C7H15 3bc R1 = CH3
OBn
4ac R~ = C7H15, R~ = H 4bc R' = CH3, R2 = H 5ac R' = C H15, R2 = CH3 5bcR'-R ?! =CH3
7ac R' = C7H15 7bc R' = CH3
ations, as illustrated in Figure 2. It has been established that zirconium enolates of a-alkoxy esters form chelated structures such as D or Eq2 Steric interactions between the endo Cp grouping and R2 disfavor E relative to D leading to a predominance of 7 in such rearrangements. In the case of the acids 4 the ZrCp, and R3 groupings would be replaced by solvated lithium ions. The silyl triflate promoted rearrangements are thought to proceed by oxonium ylide species such as F or GeBHere intermediate F, analogous to D, does not benefit from chelation but experiences steric repulsion between the carboxylic and silyl groupings. Thus, reaction by way of transition state G is favored. As expected, increasing the steric bulk of the silyl substituents enhances stereoselectivity and decreases reaction rate. Presumably, steric interactions between Ra and SiRs retard oxonium salt formation with bulky silyl groups. With a view toward the eventual synthesis of polyether natural products, we tested the applicability of this methodology to the benzyloxy ethers 480, Sac, and especially Sbc, prepared as shown in Scheme II. Surprisingly, the rearrangements were markedly less selective than the analogous alkyl systems. Thus, acid 4ac gave rise to a 60:40 mixture of allenoh 7 and 8 in only 21 % yield (Table 11, entry 1). The derived ester Sac failed to rearrange under conditions previously employed for esters Saa and
Marehall and Wang
4916 J. Org. Chem., Vol. 56, No.16,1991 Table 11. [2$] Wittig Rearrangements of Carboxymethyl l-(Benzyloxy)-3-alkyn-2-yl Ethers
Table 111. Electrophile-Induced Cyclizations of Allenolr to 2,5-Dihydrofuuranr (S I
entry 1 2
3 4 5
ether 4ac 5ac Sac Sbc 5bc
R1 C7H16 C7H16 C7H16 CHS CHS
R2
conditionsa A B D C D
H CHS CHS CHS CHS
yield 21
7
13 X-H 14 X-Bf 15 X-SePh
16
8
1 7 X-H
20
7:8 60:40
Ob
67 95 88
3367 4555 3367
OKey: A = LDA, THF, -78 OC; B = LDA, THF, -78 "C, Cp2ZrCl2;C = TMSOTf, E h N D = TESOTf, EhN. bStarting material and decomposition products recovered after 18 h at -20
18 X=Br 19 x-SePh
OC.
entry
allenol 7aa 7bb
conditionso yield X A 8 4 H A H A 8 4 H A H B 66 Br 64 Br B C 66 SePhb C 62 SePhC
5bb. Although silyl-promoted rearrangements proceeded more readily, the stereoselectivity was a modest 1:2, at best (Table 11, entries 3-5). Presumably, complexation of Li, ZrCp,, and &Si cations with the benzylic ether oxygen is responsible for the contrasting behavior of ethers 4ac, 5ac, and 5bc and 4aa, 4bb, 5aa, and 5bb. In the basepromoted reactions a tridentate complex such as H could prevent proper alignment of the enolate carbon with the triple bond. We can offer no rationale for the poor selectivity of the silyl-promoted rearrangements.
I, Key: A = AgN03, CaCOS,Me2CO-H20;B = NBS, CH2C12;C = PhSeCl, CH2C12. b17% of 16 was also isolated. e17% of 20 waa also isolated.
H
or PhSeCl (entries 7 and 8). In the latter cases, the byproducts 16 and 20 were formed.'&" These are presumed to arise from attack on the allenic double bond syn to the side chain OH, and the stereochemistry is assigned accordingly.
A possible alternative route to allene-1,5-diols through Still-Wittig rearrangement of the stannylmethyl ethers 11 was briefly examined (eq 2)." Both llac and llbc readily OH R'-=YoBn
-
