Regio- and Enantioselective Substitution of Primary Endocyclic Allylic Sulfoximines with Organocopper and Organocuprate Reagents. The Importance of Iodide for the Allylic Substitution with Organocopper Compounds

Abstract

The endocyclic N-substituted allylic sulfoximines 17-20 and 26 were synthesized from the corresponding cycloalkanones and the various (8-S-(lithiomethyl)-S-phenylsulfoximines in enantiomerically pure form in yields of 60-70% in a process involving the isomerization of the intermediate vinylic sulfoximines. Desilylation of 26 gave the parent N-H sulfoximine 27 from which the N-sulfonylsulfoximines 28 and 29 were prepared. The X-ray crystal structure of 28 was determined. The allylic sulfoximines 17-20 and 26-29 did not racemize or rearrange thermally to the corresponding allylic sulfinamides. Reaction of the allylic sulfoximines 18,28, and 29 with the organocuprate reagents 2/LiI, 35/LiI, and 47LiI led with a-selectivities of 92:8 to 99:l to the endocyclic alkenes 39 in good to high yields. Reaction of 17-20, 28, and 29 with the organocopper reagents S/LiI, 30/LiI, 31/LiI, 32/LiI, 33/LiI, 34/LiI, and 37/LiI in the presence of BF3 resulted in the formation of the exocyclic alkenes 38, 41, 43, and 45, respectively, in good to high yields with y-selectivities of 80:20 to 99: 1. The sulfonimidoyl group imparts asymmetric induction to the substitution in the range of 27-90% ee. The (8-sulfonimidoyl group leads to a preferential bond formation from the si side of the double bond. From the sulfoximines 18 and 26-29 the N-methylsulfoximine 18 and the N-tosylsulfoximine 28 showed the highest and lowest reactivity with the butylcopper reagent 32/LiI in the presence of BF3, respectively, while in the absence of BF3 only 29 reacted. The Lewis acid most likely serves to activate the N-methyl-and N-tosylsulfoximines or intermediates thereof through coordination at the sulfonimidoyl and sulfonyl group. Reaction of the sulfoximines 18 and 29 with pure Me3SiCHzCu (34) revealed a strong rate acceleration by LiI and an even stronger one by Bu4NI. This points to the existence of a heteroleptic cuprate or a related compound as reactive species. In substitutions with the Yamamoto reagents RCu/MX/BF3, the halide is important and a reaction between RCu and BF3 does not have, at least in the case of allylic sulfoximines, to be invoked. In reactions of 17-20 besides the alkenes, the sulfinamide ent-4 was formed with an ee value of 97% in high yield with retention of configuration. The absolute configuration of the exocyclic alkenes 38, 41, and 45 was determined by ozonolysis to the corresponding cycloalkanones followed by their conversion to the corresponding lactones andlor CD measurement of the former.

Asymmetric Synthesis of Cycloalkenyl and Alkenyloxiranes From Allylic Sulfoximines and Aldehydes and Application to Solid‐Phase Synthesis

“…of ClTi(NEt 2 ) 3 at Ϫ78°C in diethyl ether afforded the corresponding allylic titanium complex, which upon treatment with benzaldehyde and isobutyraldehyde at Ϫ78°C gave, as described previously, the diastereomerically pure syn-configured sulfoximine-substituted homoallylic alcohols 2a and 2b, respectively, in medium to good yields (Scheme 2). [9,10] Similarly, the new diastereomerically pure seven-membered homoallylic alcohol 2c was obtained in good yield from the allylic sulfoximine 1b [15] and benzaldehyde. NMR spectroscopic analysis of the crude reaction product showed the hydroxyalkylation to be, as in all previously described cases, highly diastereoselective (Ն 95% de) and regioselective (Ն 98:2).…”

“…Successive lithiation and titanation of the six-membered cyclic allylic sulfoximine 1a [15] with 1.1 equiv. of nBuLi and 1.2 equiv.…”

Modular Asymmetric Synthesis of Functionalized Azaspirocycles Based on the Sulfoximine Auxiliary

“…33 For the determination of the diastereoselectivity with the 1 H NMR spectrum of the crude mixture H-1 signals were used. • …”

Asymmetric Organocopper Chemistry: Cu-Catalyzed Conjugate Addition and Allylic Substitution

“…These are chiral C2 symmetrical acetals, 56 carbamates, 57 oxazolinyl thioethers 58 and sulfoximines. 59 The first report on the catalytic version is due to Backvall and van Koten, in 1995. 60 They used a Grignard reagent as primary organometallics, and a copper thiolate as chiral catalyst (15% is not yet very large as the substrate is concerned.…”